Controlled-release PTH compound
The present invention relates to a controlled-release parathyroid hormone (PTH) compound in which PTH(1-34) is reversibly conjugated to a branched polyethylene glycol. The invention further relates to a pharmaceutical composition of the compound. The compound or pharmaceutical composition is useful for treatment, control, delay or prevention of a condition that can be treated, controlled, delayed or prevented with PTH.
1. A parathyroid hormone (PTH) conjugate of formula:
or a pharmaceutically acceptable salt thereof, wherein
the unmarked dashed line indicates the attachment by an amide bond to the N-terminal nitrogen of a PTH moiety, the amino acid sequence of which consists of the sequence of SEQ ID NO:51; and the dashed line marked with the asterisk indicates attachment to a moiety
wherein
m and p are independently an integer ranging from and including 150 to 1000.
2. The PTH conjugate or pharmaceutically acceptable salt thereof of claim 1 , wherein the moiety
has a molecular weight of about 15-80 kDa.
3. The PTH conjugate or pharmaceutically acceptable salt thereof of claim 1 , wherein m and p are the same integer.
4. A pharmaceutical composition comprising the PTH conjugate or pharmaceutically acceptable salt thereof of claim 1 and at least one excipient.
5. The pharmaceutical composition of claim 4 , wherein the pharmaceutical composition has a pH of 4-6.
6. A liquid pharmaceutical composition comprising
a parathyroid hormone (PTH) conjugate of formula:
or a pharmaceutically acceptable salt thereof, and a solvent, wherein
the unmarked dashed line indicates the attachment by an amide bond to the N-terminal nitrogen of a PTH moiety, the amino acid sequence of which consists of the sequence of SEQ ID NO:51; and the dashed line marked with the asterisk indicates attachment to a moiety
wherein
m and p are independently an integer ranging from and including 150 to 1000.
7. The liquid pharmaceutical composition of claim 6 , wherein the moiety
has a molecular weight of about 15-80 kDa.
8. The liquid pharmaceutical composition of claim 7 , wherein m and p are the same integer.
9. The liquid pharmaceutical composition of claim 7 , wherein the solvent is water.