Polyglutamate-amino acid conjugates and methods
원문보기
IPC분류정보
국가/구분
United States(US) Patent
등록
국제특허분류(IPC7판)
A61K-031/00
A61K-047/42
A61K-049/00
A61K-031/337
A61K-049/14
A61K-031/704
A61K-031/4745
A61K-047/62
A61K-047/64
A61K-047/56
출원번호
US-0354547
(2016-11-17)
등록번호
US-9855338
(2018-01-02)
발명자
/ 주소
Yu, Lei
Zhao, Gang
Van, Sang
Das, Sanjib Kumar
Feng, Zhongling
Fu, Xiaoli
Wang, Xinghe
Jin, Yi
Chen, Fu
출원인 / 주소
Nitto Denko Corporation
대리인 / 주소
Knobbe, Martens, Olson & Bear, LLP
인용정보
피인용 횟수 :
0인용 특허 :
82
초록
Various biodegradable polyglutamate-amino acids comprising recurring units of the general formulae (I) and (II) are prepared. Such polymers are useful for variety of drug, biomolecule and imaging agent delivery applications.
대표청구항▼
1. A pharmaceutical composition comprising particles of an insoluble polymer conjugate dispersed in an aqueous solution, said insoluble polymer conjugate comprising a recurring unit of the formula (I) and a recurring unit of the formula (II): wherein:each n is independently 1 or 2;each A1 is oxygen
1. A pharmaceutical composition comprising particles of an insoluble polymer conjugate dispersed in an aqueous solution, said insoluble polymer conjugate comprising a recurring unit of the formula (I) and a recurring unit of the formula (II): wherein:each n is independently 1 or 2;each A1 is oxygen or NR5;each A2 is oxygen;R1 and R2 are each independently selected from the group consisting of C1-10 alkyl, C6-20 aryl, ammonium, alkali metal, a polydentate ligand, a polydentate ligand precursor with protected oxygen atoms, and a compound that comprises an agent; wherein the agent is selected from the group consisting of an anticancer drug, a targeting agent, an optical imaging agent, and a magnetic resonance imaging agent;wherein at least one of R1 and R2 is a group that comprises an agent;R3 and R4 are each independently selected from the group consisting of hydrogen, ammonium, and an alkali metal;wherein the polymer conjugate comprises an amount of the agent in the range of about 1 to about 50% (weight/weight) based on the mass ratio of the agent to the polymer conjugate; andR5 is hydrogen or C1-4 alkyl. 2. The pharmaceutical composition of claim 1, the insoluble polymer conjugate, further comprising a recurring unit of the formula (III): wherein R6 is hydrogen, ammonium, or an alkali metal. 3. The pharmaceutical composition of claim 1, wherein the compound that comprises the agent further comprises a linker group. 4. The pharmaceutical composition of claim 1, wherein the agent is an optical imaging agent. 5. The pharmaceutical composition of claim 4, wherein the optical imaging agent is selected from the group consisting of an acridine dye, a coumarine dye, a rhodamine dye, a xanthene dye, cyanine dye, and a pyrene dye. 6. The pharmaceutical composition of claim 1, wherein the agent is an anticancer drug. 7. The pharmaceutical composition of claim 6, wherein the anticancer drug is selected from the group consisting of a taxane, camptothecin, and doxorubicin. 8. The pharmaceutical composition of claim 7, wherein the taxane is selected from the group consisting of paclitaxel and docetaxel. 9. The pharmaceutical composition of claim 8, wherein paclitaxel is conjugated to the recurring unit of formula (I) at the oxygen atom attached to the C7-carbon. 10. The pharmaceutical composition of claim 8, wherein paclitaxel is conjugated to the recurring unit of formula (I) at the oxygen atom attached to the C7-carbon. 11. The pharmaceutical composition of claim 1, wherein the agent is a magnetic resonance imaging agent. 12. The pharmaceutical composition of claim 11, wherein the magnetic resonance imaging comprises a Gd(III) compound. 13. The pharmaceutical composition of claim 12, wherein the Gd(III) compound comprises: 14. The pharmaceutical composition of claim 1, wherein the polydentate ligand comprises: wherein each R7 is independently hydrogen, ammonium, or an alkali metal. 15. The pharmaceutical composition of claim 1, wherein the polydentate ligand precursor with protected oxygen atoms comprises: 16. The pharmaceutical composition of claim 1, wherein at least one n is 1. 17. The pharmaceutical composition of claim 1, wherein at least one n is 2. 18. The pharmaceutical composition of claim 1, wherein the alkali metal is sodium. 19. The pharmaceutical composition of claim 1 further comprising at least one selected from a pharmaceutically acceptable excipient, a carrier, and a diluent. 20. A method of treating, ameliorating, or diagnosing a disease or condition comprising administering an effective amount of the pharmaceutical composition of claim 1 to a mammal in need thereof. 21. The pharmaceutical composition of claim 1, wherein: n is 2;each A1 is oxygen;each A2 is oxygen;R1 is paclitaxel; andR2, R3 and R4 are each independently hydrogen or an alkali metal. 22. The pharmaceutical composition of claim 21, wherein the paclitaxel is conjugated to the recurring unit of formula (I) at the oxygen atom attached to the C2′-carbon. 23. The pharmaceutical composition of claim 21, wherein the paclitaxel is conjugated to the recurring unit of formula (I) at the oxygen atom attached to the C7-carbon. 24. A method of treating a cancer, comprising administering an effective amount of the pharmaceutical composition of claim 21 to a mammal in need thereof.
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