Injectable cross-linked collagen implant material
First Claim
1. A novel cross-linked atelopeptide collagen for use as an injectable aqueous suspension for augmenting soft tissue that:
- (a) is substantially free of residual cross-linking agent;
(b) has greater than about 15 free lysine residues per 1000 amino acid residues; and
(c) is composed substantially of fibrous particles which when in suspension in physiological saline at a concentration of 35 mg/ml exhibit a shear viscosity whose log varies linearly with the log of the shear rate and is approximated by the formula
space="preserve" listing-type="equation">log η
≦
-0.96 log γ
+2.3 where γ
is the shear rate in sec-1, log γ
is in the range of -6 to +2, and η
is the viscosity of the suspension in Pascal-sec.
7 Assignments
0 Petitions
Accused Products
Abstract
Cross-linked atelopeptide collagen that is substantially free of residual cross-linking agent is prepared by: reconstituting atelopeptide collagen from solution by neutralizing the solution at a reduced temperature and a hypotonic ionic strength; cross-linking the reconstituted fibers in an aqueous medium at a concentration of 0.1 to 10 mg/ml with glutaraldehyde under conditions that produce cross-linked collagen that when in suspension in physiological saline at a concentration of 35 mg/ml exhibits a shear viscosity whose log varies linearly with the log of the shear rate and is approximated by the formula
log η≦-0.96 log γ+2.3
where γ is the shear rate in sec-1, log γ is in the range of -6 to +2 and η is the viscosity of the suspension in Pascal-sec; optionally quenching the cross-linking reaction with an amino acid; and separating the cross-linked atelopeptide collagen from the reaction mixture. This collagen is dispersed in an isotonic aqueous medium for use in soft tissue dermal augmentation and is injectable and forms implants that have excellent persistence.
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Citations
31 Claims
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1. A novel cross-linked atelopeptide collagen for use as an injectable aqueous suspension for augmenting soft tissue that:
-
(a) is substantially free of residual cross-linking agent; (b) has greater than about 15 free lysine residues per 1000 amino acid residues; and (c) is composed substantially of fibrous particles which when in suspension in physiological saline at a concentration of 35 mg/ml exhibit a shear viscosity whose log varies linearly with the log of the shear rate and is approximated by the formula
space="preserve" listing-type="equation">log η
≦
-0.96 log γ
+2.3where γ
is the shear rate in sec-1, log γ
is in the range of -6 to +2, and η
is the viscosity of the suspension in Pascal-sec. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 26, 29, 30, 31)
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11. A process for preparing cross-linked atelopeptide collagen for use as an injectable aqueous suspension for augmenting soft tissue comprising:
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(a) reconstituting atelopeptide collagen from an acidic aqueous solution by neutralizing the solution at a reduced temperature and at a hypotonic ionic strength; (b) cross-linking the reconstituted atelopeptide collagen in an aqueous medium at a concentration of about 0.1 to about 10 mg/ml with a cross-linking agent at a concentration of about 0.001% to 0.05% by weight that forms covalent bonds with the collagen under conditions sufficient to produce a fibrous cross-linked collagen that has greater than about 15 free lysine residues per 1000 amino acid residues and that when in suspension in physiological saline at a concentration of 35 mg/ml exhibits a shear viscosity approximated by the formula
space="preserve" listing-type="equation">log η
≦
-0.96 log γ
+2.3where γ
is the shear rate in sec-1, log γ
is in the range of -6 to +2, and η
is the viscosity of the suspension in Pascal-sec; and(c) separating the cross-linked collagen from the cross-linking reaction mixture. - View Dependent Claims (12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 27, 28)
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Specification