Systems and methods for delivery of drugs
First Claim
1. A pharmaceutical formulation which comprises a CYC carrier and a drug associated with the CYC carrier, the CYC carrier being an ECC polymer which(A) comprises a plurality of polymeric molecules which have a backbone which comprises terminal units having the formula
—
- Yterm-b-Cy
(2)where Yterm is a moiety at the end of the backbone, andb is a bond or moiety which links the Cy moiety to Yterm, andCy is a moiety which is associated with other Cy moieties to provide the CYC polymer with crystallinity;
the Cy moieties in said terminal units providing at least 50% by weight of the Cy moieties in the polymeric molecules, and(B) has a crystalline melting temperature, Tp, of at least 0°
C. and a heat of fusion, Δ
H, of at least 3 J/g which result from association of the Cy moieties, Tp and Δ
H being measured on a differential scanning calorimeter (DSC) as hereinbefore described.
1 Assignment
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Accused Products
Abstract
Systems and methods for delivering drugs. Crystalline polymeric systems, referred to as CYC carriers, are associated with the drugs, through chemical bonding or through physical association. The crystallinity of the CYC carriers results from the presence of crystallizable side chains, for example long chain n-alkyl moieties, which results in relatively low and sharp melting temperatures. One class of CYC carriers, referred to as CYSC polymers, have a majority of the crystallizable side chains pendant from the polymer backbone. Another class of CYC carriers, referred to as ECC polymers, have a majority of the crystallizable side chains attached to terminal units of the polymer backbone. The ECC polymers can for example be obtained by modification of PLGA polymers. The CYC carriers in another class are non-polymeric. Some CYC carriers, referred to as CYC assemblies, have enhanced crystallinity as a result of the physical association of crystallizable moieties which are present in different types of molecule, for example between a polymer containing crystallizable moieties and a monomer containing crystallizable moieties. Preferably the CYC carrier is bioerodable.
137 Citations
28 Claims
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1. A pharmaceutical formulation which comprises a CYC carrier and a drug associated with the CYC carrier, the CYC carrier being an ECC polymer which
(A) comprises a plurality of polymeric molecules which have a backbone which comprises terminal units having the formula
—- Yterm-b-Cy
(2)where Yterm is a moiety at the end of the backbone, and b is a bond or moiety which links the Cy moiety to Yterm, and Cy is a moiety which is associated with other Cy moieties to provide the CYC polymer with crystallinity; the Cy moieties in said terminal units providing at least 50% by weight of the Cy moieties in the polymeric molecules, and (B) has a crystalline melting temperature, Tp, of at least 0°
C. and a heat of fusion, Δ
H, of at least 3 J/g which result from association of the Cy moieties, Tp and Δ
H being measured on a differential scanning calorimeter (DSC) as hereinbefore described. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15)
- Yterm-b-Cy
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16. A pharmaceutical formulation which comprises a CYC carrier and a drug associated with the CYC carrier, the CYC carrier being a block copolymer comprising a plurality of block copolymer molecules which comprise a first polymeric block and a second polymeric block,
the first polymeric block having a backbone which is bioerodable and which comprises linkages having the formula
-Dnd-Q-Ene--
(Q1)where Q is —
O—
, —
NH—
or —
S—
,nd is 0 or 1, ne is 0 or 1, D is —
CO—
, andE is —
CO—
or —
CO—
O—and the second polymeric block comprising repeating units having the formula - View Dependent Claims (17)
-
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18. A pharmaceutical formulation which comprises a CYC carrier and a drug associated with the CYC carrier, the CYC carrier being a non-polymeric compound which
(A) has the formula
Q(-b-Cy)q-
(4)wherein q is least 2, e.g. 3-8, Q is a moiety having a valence of at least q, b is a bond or a moiety linking the Cy moiety to the Q moiety, and Cy is a moiety which is associated with other Cy moieties to provide the CYC polymer with crystallinity, and (B) has a crystalline melting temperature, Tp, of at least 0°
C. and a AH of at least 3 J/g which results from association of the Cy moieties; and
-
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19. A pharmaceutical formulation which comprises a CYC carrier and a drug associated with the CYC carrier, the CYC carrier being a CYC assembly of (i) a polymer which is a CYC polymer as hereinbefore defined except that the polymer does not necessarily have a Tp of at least 0°
- C. and a Δ
H of at least 4 J/g, and (ii) a compound which contains a Cy moiety and which is intimately mixed with the polymer but is not covalently linked to the polymer, the assembly having a crystalline melting temperature, Tp, of at least 0°
C. and a Δ
H of at least 3 J/g which results from association of the Cy moieties.
- C. and a Δ
-
20. A pharmaceutical formulation which comprises a CYC carrier and a drug associated with the CYC carrier, the CYC carrier being an SSP polymer, an SSP polymer being defined as a polymer which
(1) has a crystalline melting temperature, Tp, of at least 25° - C., and a Δ
H of at least 5 J/g; and(2) comprises polymeric molecules having a backbone which comprises (a) repeating units which do not contain hydrophilic moieties, and have the formula (1) below - View Dependent Claims (28)
- C., and a Δ
- 21. A pharmaceutical formulation which comprises a CYC carrier as hereinbefore defined and a drug associated with the CYC carrier.
Specification