Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Implant or insert
Reexamination Certificate
2000-08-01
2002-04-02
Page, Thurman K. (Department: 1615)
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Implant or insert
C424S426000, C428S398000
Reexamination Certificate
active
06365172
ABSTRACT:
STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT
Not applicable.
FIELD OF THE INVENTION
This invention relates to new and useful fiber-forming biabsorbable polymeric materials, such as bioabsorbable triglycolic acid poly(ester-amides)s, derived from reacting diamidediols with a diacid chloride deriviative of 3,6-dioxaoctanedioic acid, also known as “triglycolic acid”. This invention also relates to new and useful diol terminated poly(ester-amide)s of triglycolic acid made by the polymerization of diamine diols with triglycolic acid poly(ester-amides)s, and to products of reacting such diol terminated poly(ester-amide)s with cyclic monomers to produce block copolymers. This invention further relates to methods of making new and useful fiberous bioabsorbable implants, including surgical sutures and molded devices, of such block copolymers or other polymeric materials.
BACKGROUND OF THE INVENTION
Since the first synthetic absorbable suture made from braided multifilaments of poly(glycolic acid) was introduced in about the year 1970, advancements in the design and synthesis of bioabsorbable polymers have resulted in continuous improvements in absorbable suture products.
In addition to the suture application, high strength, highly flexible, tough, and durable fibers that possess a prolonged flex fatigue life are needed for use as braided, knitted, woven, or non-woven implants to augment and temporarily reinforce autologous tissue grafts or preserve as scaffolds for tissue regeneration. One example of such an implant is known as a ligament augmentation device (LAD) used to reconstruct the anterior cruciate ligament (ACL) of the knee. Bioabsorbable fibers of the prior art, such as poly(L-lactic acid) (PLA), have not been successful in this application due to low flex fatigue life, shedding of wear debris due to the brittle nature of the fibers, and prolonged bioabsorption time.
Other well known uses for bioabsorbable polymers that have not been fully realized or perfected with available polymers of the prior art include scaffolds for tissue engineering, bioabsorbable knitted vascular grafts, drug-releasing devices, growth factor-releasing implants for bone and tissue regeneration, and fiber-reinforced composites for orthopedic applications. For example, composites of polymers reinforced with dissimilar materials, such as dissolvable glass fiber reinforced poly(lactic acid) are unacceptable for use as implants, the following reasons. Although dissolvable glass fibers provide high modulus needed for the composite to have high initial strength and stiffness, adhesion between glass and polymer invariably fails prematurely in vivo resulting in devices with unacceptable in vivo performance.
Self-reinforced composites were developed as an alternative to composites of polymers reinforced with dissimilar materials, such as those described above. In self-reinforced fiber composites both reinforcing fibers and matrix are made of the same material. Although the stiffness is lower than can be achieved with glass fibers, this alternative type of composite ensures good adhesion between fiber and matrix and thus offers the possibility of longer lasting in vivo strength. Self-reinforced poly(glycolic acid) (PGA) rods, pins and screws made by hot pressing or sintering PGA fibers have shown promise in clinical use. The main disadvantage of PGA in general is that it degrades too fast for orthopedic applications and releases an excessive concentration of acidic degradation products into the surrounding tissue.
Despite the advancements in the art of producing polymeric materials and methods for making polymeric materials suitable for use in sutures, molded devices, and similar surgical devices. Specifically, there continues to be a need for new fibers that are monofilament, has a high initial tensile knot strength, retain useful strength in vivo for about two weeks or longer, are fully bioabsorbed within a few months after strength loss, and have very low bending stiffness.
BRIEF SUMMARY OF THE INVENTION
The present invention consists of a biabsorbable polymer of the general formula (I):
wherein, x is from 2 to 10, m and n are independently from 0 to 2000, p is from 10 to 2000, and A is comprised of from 0 to 90 mole % A1 in combination with other structures selected from the group consisting of A2 and A3, wherein:
A1 is defined by the formula (II): —(CH
2
)
y
—, wherein y is from 2 to 10;
A2 is defined by the formula (III):
wherein R
1
is selected from the group consisting of:
i) a linear alkene having from 1 to 5 carbon atoms;
ii) an ester defined by the formula(IV): —(CH
2
)
x1
—O—(CH
2
)
y1
—, wherein x1 (the end attached to the amide carbonyl) is from 1 to 4 and y1 (the end attached to the ester oxygen) is independently from 2 to 6; and
iii) a benzyl alkane of the formula(V): —(CH
2
)
x2
—C
6
H
4
— wherein the —(CH
2
)
x2
end of the benzyl alkane is covalently attached to the amide carbonyl of formula III, and x2 is from 0 to 1; and
iv) an alkyl benzyl ester of the formula(VI):
—(CH
2
)
x3
—C
6
H
4
—O—(CH
2
)
y3
—,
wherein the —(CH
2
)
x3
end of the alkyl benzyl ester is attached to the amide carbonyl of formula III, x3 is from 0 to 1, the (CH
2
)
y3
— end of the alkyl benzyl ester is attached to the ester oxygen of formula I, and y3 is independently from 2 to 6; and
R
2
is selected from the group consisting of linear alkylenes having from 2 to 10 carbon atoms; and
A3 is defined by the following structure:
wherein R
3
is a divalent aliphatic or aromatic hydrocarbon radical having from 3 to about 8 carbon atoms; and
E
2
is defined by a formula selected from the group of formulae consisting of:
formula (V): [—CO—CHR
4
—O—], wherein R
4
is selected from the group consisting of —H (from glycolide) and —CH
3
(from lactide);
formula (VI): [—CO—O—(CH
2
)
3
—O—];
formula (VII): [—CO—CH
2
—O—(CH
2
)
2
—O—];
formula (VIII): [—CO—(CH
2
)
5
—O—]; and
combinations of formula V to VIII; and
E
1
has the same structure as E
2
except that the orientation of the formula of E
1
is reversed.
In an alternative embodiment, the invention is the bioabsorbable polymer of general formula (I), above, wherein x is 2, and except as indicated all the other variables in the formula are defined as described above, except that:
A2 is defined by formula (III):
wherein: R
1
is selected from the group consisting of:
i) a linear alkene having from 1 to 5 carbon atoms;
ii) an ester defined by formula(IV): —(CH
2
)
x1
—O—(CH
2
)
y1
—, wherein the —(CH
2
)
x1
end of the ester is attached to the amide carbonyl of formula (III), x1 is from 1 to 4 and y1 is independently from 2 to 6;
iii) a benzyl alkane of formula(V):
wherein the —(CH
2
)
x2
end of the benzyl alkane is covalently attached to the amide carbonyl of formula III, and x2 is from 0 to 1; and
iv) an alkyl benzyl ether of formula(VI):
wherein the —(CH
2
)
x3
end of the alkyl benzyl ester is attached to the amide carbonyl of formula III, x3 is from 0 to 1, the (CH
2
)
y3
— end of the alkyl benzyl ester is attached to the ester oxygen of formula I, and y3 is independently from 2 to 6; and
R
2
is selected from the group consisting of linear alkyenes having from 4 to 1 0 carbon atoms.
The present invention also consists of bioabsorbable materials made from the bioabsorbable polymer of the invention designed for in vivo use or implantation, including but not limited to bioabsorbable sutures, and a self-reinforced device comprised of fused or sintered fibers of the bioabsorbable polymer. The present invention further consists of a method of making self-reinforced materials from the bioabsorbable polymer of this invention.
DETAILED DESCRIPTION OF THE INVENTION
The diacidchloride derivative of 3,6-dioxaoctanedioic acid, commonly known as “triglycolyl chloride”, has been discovered in the present invention to be an ideal monomer or comonomer for polymerization with diamidediols to produce poly(ester-amide)s capable of forming flexible, tenacious monofilament fibers with adequate bioabsorption time for use as surgic
BioAmide, Inc.
Frenchick Grady J.
Fubara Blessing
King Karen B.
Michael & Best & Friedrich LLP
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