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 400 to 500.
2. The PTH conjugate or pharmacologically acceptable salt thereof of claim 1 , wherein the moiety
has a molecular weight of about 40 kDa.
3. The PTH conjugate or pharmacologically acceptable salt thereof of claim 1 , wherein m and p are the same integer.
4. The PTH conjugate or a pharmacologically acceptable salt thereof of claim 1 , wherein m and p are about 450.
5. A pharmaceutical composition comprising the PTH conjugate or pharmaceutically acceptable salt thereof of claim 1 and at least one excipient.
6. The pharmaceutical composition of claim 5 , wherein the pharmaceutical composition has a pH of 4-6.
7. 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 400 to 500.
8. The liquid pharmaceutical composition of claim 7 , wherein the moiety
has a molecular weight of about 40 kDa.
9. The liquid pharmaceutical composition of claim 7 , wherein m and p are the same integer.
10. The liquid pharmaceutical composition of claim 7 , wherein m and p are about 450.
11. The liquid pharmaceutical composition of claim 7 , wherein the solvent is water.