Botulinum toxin formulations and methods of use thereof in plantar fascitis with extended duration of effect

A method of treating plantar fasciitis in an individual in need thereof, the method comprising:

• administering to the individual by injection to one or more muscles or fascia causing the plantar fasciitis in the individual a composition comprising:
• a pharmaceutically acceptable diluent for injection;
• a botulinum toxin component selected from the group consisting of a botulinum toxin, a botulinum toxin complex, or a reduced botulinum toxin complex;
• and
• a positively charged carrier component comprising a positively charged polylysine backbone having covalently attached thereto one or more positively charged efficiency groups having an amino acid sequence of (gly)p-RGRDDRRQRRR-(gly)q (SEQ ID NO:
• 1), (gly)p-YGRKKRRQRRR-(gly)q (SEQ ID NO:
• 2) or (gly)p-RKKRRQRRR-(gly)q (SEQ ID NO:
• 3), wherein the subscripts p and q are each independently an integer of from 0 to 20;
• wherein the botulinum toxin component is administered to the individual in a treatment dose amount of about 50 U to about 200 U per injection treatment.
• wherein the positively charged carrier is non-covalently associated with the botulinum component;
• and
• wherein the injection of the composition provides a single treatment dose having at least about a six-month duration of effect in reducing the symptoms of plantar fasciitis in the individual, thereby extending treatment interval duration for the individual.

A pharmaceutical composition in a sterile injectable formulation for use in administering botulinum toxin to achieve an extended duration therapeutic effect in an individual with plantar fasciitis,

• said composition comprising a pharmaceutically acceptable diluent suitable for injection;
• a botulinum toxin component in a treatment dose of 50 U to 200 U, wherein said botulinum toxin component is selected from the group consisting of a botulinum toxin complex, a reduced botulinum toxin complex, or a botulinum toxin;
• and
• a positively charged carrier component comprising a positively charged polylysine backbone having covalently attached thereto one or more positively charged efficiency groups having an amino acid sequence of (gly)p-RGRDDRRQRRR-(gly)q (SEQ ID NO:
• 1), (gly)p-YGRKKRRQRRR-(gly)q (SEQ ID NO:
• 2) or (gly)p-RKKRRQRRR-(gly)q (SEQ ID NO:
• 3), wherein the subscripts p and q are each independently an integer of from 0 to 20;
• wherein the positively charged carrier is non-covalently associated with the botulinum toxin component;
• and
• wherein said treatment dose of the composition achieves the extended duration therapeutic effect having at least about a six-month duration of effect in the individual administered said formulation by injection.

A pharmaceutical composition in a sterile injectable formulation for use in reducing the symptoms of plantar fasciitis in an individual in need thereof, said composition comprising:

• a botulinum toxin component in a dose of about 50 U to about 200 U, said botulinum toxin component selected from the group consisting of a botulinum toxin complex, a reduced botulinum toxin complex, or a botulinum toxin,
• a positively charged carrier component comprising a positively charged polylysine backbone having covalently attached thereto one or more positively charged efficiency groups having an amino acid sequence of (gly)p-RGRDDRRQRRR-(gly)q (SEQ ID NO:
• 1), (gly)p-YGRKKRRQRRR-(gly)q (SEQ ID NO:
• 2) or (gly)p-RKKRRQRRR-(gly)q (SEQ ID NO:
• 3), wherein the subscripts p and q are each independently an integer of from 0 to 20;
• and
• a pharmaceutically acceptable diluent for injection;
• wherein the positively charged carrier is non-covalently associated with the botulinum toxin component;
• and
• wherein said dose of the composition provides a single treatment having at least about a six-month duration of effect in reducing the symptoms of plantar fasciitis in the individual, thereby extending treatment interval duration for the individual.

A sterile injectable composition comprising:

• a botulinum toxin component selected from the group consisting of a botulinum toxin, a botulinum toxin complex, or a reduced botulinum toxin complex, in a dosage amount selected from about 50 U to about 200 U;
• and
• a positively charged carrier component comprising a positively charged polylysine backbone having covalently attached thereto one or more positively charged efficiency groups having an amino acid sequence of (gly)p-RGRDDRRQRRR-(gly)q (SEQ ID NO:
• 1), (gly)p-YGRKKRRQRRR-(gly)q (SEQ ID NO:
• 2) or (gly)p-RKKRRQRRR-(gly)q (SEQ ID NO:
• 3), wherein the subscripts p and q are each independently an integer of from 0 to 20;
• and
• a pharmaceutically acceptable diluent for injection;
• wherein the positively charged carrier is non-covalently associated with the botulinum toxin component;
• and
• wherein said positively charged carrier is present in said pharmaceutical composition in an amount selected to provide a ratio of about 0.234 μg per unit of botulinum toxin component.

A method of treating an individual with plantar fasciitis in need of treatment with injectable botulinum toxin, wherein the method of treatment comprises a treatment course having multiple treatment intervals with prolonged duration of effect and duration time between each treatment interval, the treatment course comprising:

• administering by injection an initial treatment dose of a sterile injectable composition into one or more muscles or fascia causing plantar fasciitis in the individual in need of treatment to achieve a therapeutic effect of reducing the symptoms of plantar fasciitis following the initial treatment with the composition;
• wherein the composition comprises a pharmaceutically acceptable diluent suitable for injection;
• a botulinum toxin component selected from the group consisting of a botulinum toxin, a botulinum toxin complex, or a reduced botulinum toxin complex;
• and
• a positively charged carrier component comprising a positively charged polylysine backbone having covalently attached thereto one or more positively charged efficiency groups having an amino acid sequence of (gly)p-RGRDDRRQRRR-(gly)q (SEQ ID NO:
• 1), (gly)p-YGRKKRRQRRR-(gly)q (SEQ ID NO:
• 2) or (gly)p-RKKRRQRRR-(gly)q (SEQ ID NO:
• 3), wherein the subscripts p and q are each independently an integer of from 0 to 20;
• wherein the botulinum toxin component is administered to the individual in a treatment dose of about 50 U to about 200 U per injection treatment;
• wherein the positively charged carrier is non-covalently associated with the botulinum toxin component;
• wherein the initial treatment dose of the composition administered by injection to the individual provides a therapeutic duration of effect lasting through at least about six months;
• and
• administering subsequent treatment doses of the composition by injection to the individual at treatment intervals comprising a duration of greater than or equal to about six months to at least about ten months following the initial treatment dose and between each subsequent treatment dose.

A method of treating plantar fasciitis in an individual in need thereof, the method comprising:

• topically administering to the skin overlying to one or more muscles or fascia associated with the plantar fasciitis in the individual, a topical composition comprising:
• a pharmaceutically acceptable diluent suitable for topical administration;
• an effective amount of a botulinum toxin component selected from the group consisting of a botulinum toxin, a botulinum toxin complex, or a reduced botulinum toxin complex;
• and
• an effective amount of a carrier component comprising a polymeric backbone having covalently attached thereto one or more positively charged efficiency groups,
• wherein the carrier component is a positively charged carrier, with the backbone being a positively charged polymeric backbone, or a lipophilic carrier, with the backbone being a hydrophobic oligomeric or polymeric backbone;
• and
• wherein the carrier component is non-covalently associated with the botulinum toxin component,
• thereby treating plantar fasciitis.

A pharmaceutical composition in a topical formulation for use in treating plantar fasciitis in an individual in need thereof by topical administration to the skin overlying one or more muscles or fascia associated with the plantar fasciitis in said individual, said composition comprising:

• a pharmaceutically acceptable diluent suitable for topical administration;
• an effective amount of a botulinum toxin component selected from the group consisting of a botulinum toxin complex, a reduced botulinum toxin complex, or a botulinum toxin;
• and
• an effective amount of a carrier component comprising a polymeric backbone having covalently attached thereto one or more positively charged efficiency groups,
• wherein the carrier component is a positively charged carrier, with the backbone being a positively charged polymeric backbone, or a lipophilic carrier, with the backbone being a hydrophobic oligomeric or polymeric backbone;
• and
• wherein the carrier component is non-covalently associated with the botulinum toxin component,
• thereby treating plantar fasciitis.

A method of treating plantar fasciitis in an individual in need thereof, the method comprising:

• administering to the individual by a single injection to a muscle or fascia of the plantar fascia of the individual, a composition comprising:
• a pharmaceutically acceptable diluent for injection;
• a botulinum toxin component that is botulinum toxin of serotype A having a molecular weight of 150 kDa without accessory non-toxin proteins;
• a positively charged carrier having the amino acid sequence RKKRRQRRRG-(K)15-GRKKRRQRRR (SEQ ID NO:
• 4);
• wherein the botulinum toxin component is administered to the individual in a treatment dose amount of about 80 U or about 120 U per injection treatment;
• wherein the positively charged carrier is non-covalently associated with the botulinum component;
• and
• wherein the injection of the composition provides a single treatment dose having at least about a 26-week duration of effect in reducing pain associated with the plantar fasciitis of the individual,
• thereby extending treatment interval duration for the individual.

A pharmaceutical composition in a sterile injectable formulation for use in treating plantar fasciitis in an individual in need thereof, said composition comprising:

• a botulinum toxin component in a dose of about 80 U or about 120 U, said botulinum toxin component consisting of serotype A having a molecular weight of 150 kDa without accessory non-toxin proteins,
• a positively charged carrier having the amino acid sequence RKKRRQRRRG-(K)15-GRKKRRQRRR (SEQ ID NO:
• 4);
• and
• a pharmaceutically acceptable diluent for injection;
• wherein the positively charged carrier is non-covalently associated with the botulinum toxin component;
• and
• wherein said dose of the composition provides a single injection treatment to a muscle or fascia of the plantar fascia of the individual to give at least about a 26-week duration of effect in reducing pain associated with the plantar fasciitis of the individual, thereby extending treatment interval duration for the individual.

A method of treating plantar fasciitis in an individual in need thereof, the method comprising:

• administering to the individual by injection to one or more muscles or fascia associated with the plantar fasciitis of the individual a composition comprising:
• a pharmaceutically acceptable diluent for injection;
• a botulinum toxin component that is botulinum toxin of serotype A having a molecular weight of 150 kDa without accessory non-toxin proteins;
• a positively charged carrier having the amino acid sequence RKKRRQRRRG-(K)15-GRKKRRQRRR (SEQ ID NO:
• 4);
• wherein the botulinum toxin component is administered to the individual in a treatment dose amount of about 240 U per injection treatment;
• wherein the positively charged carrier is non-covalently associated with the botulinum component;
• and
• wherein the injection of the composition provides a single treatment dose that reduces pain associated with plantar fasciitis by at least 50% 8 weeks following treatment.

A pharmaceutical composition in a sterile injectable formulation for use in treating plantar fasciitis in an individual in need thereof, said composition comprising:

• a botulinum toxin component in a dose of about 240 U, said botulinum toxin component consisting of serotype A having a molecular weight of 150 kDa without accessory non-toxin proteins,
• a positively charged carrier having the amino acid sequence RKKRRQRRRG-(K)15-GRKKRRQRRR (SEQ ID NO:
• 4);
• and
• a pharmaceutically acceptable diluent for injection;
• wherein the positively charged carrier is non-covalently associated with the botulinum toxin component;
• and
• wherein said dose of the composition provides a single treatment that reduces pain associated with plantar fasciitis by at least 50% 8 weeks following treatment.