Dental varnishes that release specifically targeted antimicrobial peptides and/or fluoride

1. A dental varnish system for the sustained delivery of a specifically targeted antimicrobial peptide (STAMP), said varnish system comprising:

a first component that is a dry powder, said first component comprising a specifically targeted antimicrobial peptide (STAMP) comprising the amino acid sequence TFFRLFNRSFTQAL GKGGGKNLRIIRKGIHIIKKY (C16G2, SEQ ID NO:1); and

a second component that is a fluid, said second component comprising a varnish solution wherein said solution comprises an aminomethacrylate polymer and ethanol 200 proof USP;

where combination of said first component with said second component provides a fluid varnish formulation in which said ethanol is a solvent for said dry powder first component, where said formulation when applied to the surface of a tooth delivers an effective amount of said STAMP that retains antimicrobial activity to said surface of said tooth for at least 4 hours after application.

2. The varnish system of claim 1 , wherein:

said varnish formulation provides release of an effective amount of said STAMP for at least 6 hours after application, or for at least 8 hours after application, or for at least 12 hours after application, or for at least 24 hours after application, or for at least 48 hours after application; and/or

said varnish formulation provides a release of at least 80% of said STAMP or AMP within about 8 hours or less, or within about 6 hours or less, or within about 4 hours or less, or within about 2 hours or less, or within about 1 hour or less.

3. The varnish system of claim 1 , wherein said first component comprises said STAMP and a pH adjuster.

4. The varnish system of claim 1 , wherein:

combination of said first component with said second component in substantially equal parts as fluid, or where the first component is a dry powder in a ratio of powder to fluid second component ranging from about 100 mg powder up to about 260 mg powder mixed with 1 ml fluid second component produces a formulation having a pH ranging from about 5.0 to about 7.5, or from about 5.9 to about 6.1, and containing said STAMP or AMP in a form and concentration that is effective to kill S. mutans ; or

said first component is a dry powder in a ratio of powder to fluid second component of about 127 mg dry powder to 1 ml fluid second component; or

said first component is a dry powder in a ratio of powder to fluid second component of about 190 mg dry powder to 1 ml fluid second component; or

said first component is a dry powder in a ratio of powder to fluid second component of about 254 mg dry powder to 1 ml fluid second component; or

said first component contains only said specifically targeted antimicrobial peptide; or

first component contains only said specifically targeted antimicrobial peptide, and a thickener; or

said first component contains only said specifically targeted antimicrobial peptide and a preservative; or

said first component contains only said specifically targeted antimicrobial peptide, a thickener, and a preservative; and/or wherein:

the second component comprises a buffer; and/or

said first component or the second component further comprises a salt to adjust tonicity; and/or

said first component or said second component further comprises a bulking agent; and/or

said first component or said second component further comprises one or more solubilizing/emulsifying agents; and/or

said first component or said second component further comprises a chelating agent; and/or

said first component or said second component further comprises a preservative; and/or

said first component or said second component further comprises a sweetener; and/or

said first component or said second component further comprises a colorant; and/or

said first component or said second component further comprises flavoring agent; and/or

said first component and/or said second component further comprises a thickener; and/or

said second component comprises a cationic (positively charged, permanently or pH dependent) random co-polymer based on dimethylaminoethyl methacrylate; and/or

said second component comprises Poly(butyl methacrylate-co-(2-dimethylaminoehtyl) methacrylate-co-methyl methacrylate) at 1:2:1 mol ratio.

5. The varnish system of claim 1 , wherein:

said second component comprises about 28.6 varnish polymer, about 60% ethanol, and about 11.4% flavor; and/or

said first component comprises a powder comprising about 10.7% antimicrobial peptide, about 84% Mannitol, about 1.6% Histidine, about 4.2% sucralose and said first component is combined with the second component in a ratio of about 127 mg dry powder to 1 ml of said second component (varnish solution); or

said first component comprises a powder comprising about 14.3% antimicrobial peptide, about 80% Mannitol, about 1.6% histidine, about 4.2% sucralose; and

said first component is combined with the second component in a ratio of about 190 mg dry powder to 1 ml of said second component (varnish solution); or

said first component comprises a powder comprising about 21.4% antimicrobial peptide, about 73% mannitol, about 1.6% histidine, about 4.2% sucralose; and said first component is combined with the second component in a ratio of about 254 mg dry powder to 1 ml of said second component (varnish solution); or

said second component comprises poly(butyl methacrylate-co-(2-dimethylaminoehtyl) methacrylate-co-methyl methacrylate at 1:2:1 mol ratio and about 11.4% flavor in 60% ethanol.

6. The varnish system of claim 1 , wherein:

when said first component is combined with said second component said system forms a varnish comprising:

a specifically targeted antimicrobial peptide;

D-mannitol;

L-histidine;

Amino Methacrylate Copolymer; and

ethanol; or

wherein combination of said first component with said second component provides a varnish formulation selected from the group consisting of:

Component

Function

Amount per dose

C16G2 STAMP

Active (anti-S. mutans)

13.60

mg

agent

D-Mannitol, USP

Bulking agent

105.92

mg

L-Histidine, USP

Buffer

1.97

mg

Sucralose, NF

Flavoring Agent

5.33

mg

Ethanol, 200 proof USP

Solvent

521.57

mg

Watermelon, Lavender,

Flavoring agent

99.09

mg

Mint Flavor

Amino Methacrylate

Polymer

249.26

mg

Copolymer, USP

FD&C Blue No. 1

Coloring Agent

0.09

mg

Sodium Hydroxide, NF

In process pH

q.s. to pH 6.0 ± 0.1,

adjustment

NF = National Formulary,

q.s. = quantity sufficient;

USP = United States Pharmacopeia

and

Component

Function

Amount per dose

C16G2 STAMP

Active Agent

27.21

mg

D-Mannitol, USP

Bulking agent

152.33

mg

L-Histidine, USP

Buffer

2.95

mg

Sucralose, NF

Flavoring Agent

8.00

mg

Ethanol, 200 proof, USP

Solvent

521.57

mg

Watermelon, Lavender,

Flavoring agent

99.09

mg

Mint Flavor

Amino Methacrylate

Polymer

249.26

mg

Copolymer, USP

FD&C Blue No. 1

Coloring Agent

0.09

mg

Sodium Hydroxide, NF

In process pH

q.s. to pH 6.0 ± 0.1,

adjustment

and

Component

Function

Amount per dose

C16G2STAMP

Active Agent

54.43

mg

D-Mannitol, USP

Bulking agent

184.97

mg

L-Histidine, USP

Buffer

3.94

mg

Sucralose, NF

Flavoring Agent

10.67

mg

Ethanol, 200 proof USP

Solvent

521.57

mg

Watermelon, Lavender,

Flavoring agent

99.09

mg

Mint Flavor

Amino Methacrylate

Polymer

249.26

mg

Copolymer, USP

FD&C Blue No. 1

Coloring Agent

0.09

mg

Sodium Hydroxide, NF

In process pH

q.s. to pH 6.0 ± 0.1.

adjustment

7. The varnish system of claim 1 , wherein said first component and/or said second component further comprises a fluoride.

8. A dental varnish for the sustained delivery of a specifically targeted antimicrobial peptide (STAMP), said varnish comprising:

a specifically targeted antimicrobial peptide (STAMP) comprising the amino acid sequence TFFRLFNRSFTQAL GKGGGKNLRIIRKGIHIIKKY (C16G2, SEQ ID NO:1); and

a varnish solution comprising an aminomethacrylate polymer and ethanol 200 proof USP;

where said dental varnish provides a fluid varnish formulation in which said ethanol is a solvent for said specifically targeted antimicrobial peptide, where said formulation when applied to the surface of a tooth delivers a tooth and delivery of an effective amount of said STAMP that retains antimicrobial activity to said surface of said tooth for at least 4 hours after application.

9. The varnish of claim 8 , wherein:

said varnish provides release of an effective amount of said STAMP for at least 6 hours after application, or for at least 8 hours after application, or for at least 12 hours after application, or for at least 24 hours after application, or for at least 48 hours after application; and/or

said varnish formulation provides a release of at least 80% of said STAMP within about 8 hours or less, or within about 6 hours or less, or within about 4 hours or less, or within about 2 hours or less, or within about 1 hour or less.

10. The varnish of claim 8 , wherein:

said varnish solution comprises a cationic (positively charged, permanently or pH dependent) random co-polymer based on dimethylaminoethyl methacrylate; or

said varnish solution comprises Poly(butyl methacrylate-co-(2-dimethylaminoehtyl) methacrylate-co-methyl methacrylate) at 1:2:1 mol ratio.

11. The varnish of claim 8 , wherein said varnish comprises one or more agents selected from the group consisting of a bulking agent, a buffer, a flavoring agent, a solvent, an emulsifying agent, a chelating agent, a coloring agent, a sweetener, and an in process pH adjustor.

12. The varnish of claim 8 , wherein

said varnish comprises:

a specifically targeted antimicrobial peptide;

D-mannitol;

L-histidine;

Amino Methacrylate Copolymer; and

ethanol; or

said varnish comprises a formulation selected from the group consisting of:

Component

Function

Amount per dose

C16G2 STAMP

Active (anti-S. mutans)

13.60

mg

agent

D-Mannitol, USP

Bulking agent

105.92

mg

L-Histidine, USP

Buffer

1.97

mg

Sucralose, NF

Flavoring Agent

5.33

mg

Ethanol, 200 proof USP

Solvent

521.57

mg

Watermelon, Lavender,

Flavoring agent

99.09

mg

Mint Flavor

Amino Methacrylate

Polymer

249.26

mg

Copolymer, USP

FD&C Blue No. 1

Coloring Agent

0.09

mg

Sodium Hydroxide, NF

In process pH

q.s. to pH 6.0 ± 0.1,

adjustment

NF = National Formulary,

q.s. = quantity sufficient;

USP = United States Pharmacopeia

and

Component

Function

Amount per dose

C16G2 STAMP

Active Agent

27.21

mg

D-Mannitol, USP

Bulking agent

152.33

mg

L-Histidine, USP

Buffer

2.95

mg

Sucralose, NF

Flavoring Agent

8.00

mg

Ethanol, 200 proof, USP

Solvent

521.57

mg

Watermelon, Lavender,

Flavoring agent

99.09

mg

Mint Flavor

Amino Methacrylate

Polymer

249.26

mg

Copolymer, USP

FD&C Blue No. 1

Coloring Agent

0.09

mg

Sodium Hydroxide, NF

In process pH

q.s. to pH 6.0 ± 0.1,

adjustment

and

Component

Function

Amount per dose

C16G2 STAMP

Active Agent

54.43

mg

D-Mannitol, USP

Bulking agent

184.97

mg

L-Histidine, USP

Buffer

3.94

mg

Sucralose, NF

Flavoring Agent

10.67

mg

Ethanol, 200 proof USP

Solvent

521.57

mg

Watermelon, Lavender,

Flavoring agent

99.09

mg

Mint Flavor

Amino Methacrylate

Polymer

249.26

mg

Copolymer, USP

FD&C Blue No. 1

Coloring Agent

0.09

mg

Sodium Hydroxide, NF

In process pH

q.s. to pH 6.0 ± 0.1.

adjustment

13. The varnish of claim 8 , wherein said first formulation and/or said dental varnish further comprises a fluoride.

14. A dental varnish kit, said kit comprising:

a container containing dental varnish according to claim 8 .

15. A kit for providing a dental varnish system of claim 1 , said kit comprising:

a container containing said first component; and

a second container containing said second component.