EP0697218A2
Expired / Lapsed
EP
⏱️ 0.0 years remaining
Method of preparing cross-linked biomaterial compositions for use in tissue augmentation
Assignee: Collagen Aesthetics Inc
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Filing: 1995-08-03
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Granted: —
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Expires: 2015-08-03
Abstract
Abstract The present invention discloses a novel method for preparing crosslinked biomaterial compositions for use in the augmentation of soft or hard tissue. In general, the method comprises mixing a biocompatible polymer, which is preferably collagen, with a sterile, dry crosslinking agent, which is preferably a synthetic hydrophilic polymer such as a functionally activated polyethylene glycol. Also provided are preferred processes for preparing sterile, dry crosslinking agents contained within syringes for use in the method of the invention. Methods for sterilization of the crosslinking agent include, but are not limited to, sterile filtration, aseptic processing, and e-beam or gamma irradiation. Methods for providing augmentation of soft or hard tissue using crosslinked biomaterial compositions prepared according to the method of the invention are also disclosed.
Inventors
- 👤 Woonza M. Rhee
- 👤 Richard A. Berg
- 👤 Joel S. Rosenblatt
- 👤 Jacqueline A. Schroeder
- 👤 Larry J. Braga
- 👤 Thomas L. Smestad
- 👤 Abigal Freeman
Bibliographic Details
Application Number
—
Jurisdiction
EP
Data Source
google_patents
Last Synchronized
2026-10-23 15:27
CPC Classifications
C; C08; C08H; C08H1/00; C08H1/06; A; A61; A61K; A61K47/00; A61K47/50; A61K47/51; A61K47/56; A61K47/59; A61K47/60; A61K47/61; A61L; A61L24/00; A61L24/04; A61L24/08; A61L26/00; A61L26/0009; A61L26/0028; A61L26/0033; A61L27/00; A61L27/14; A61L27/18; A61L27/20; A61L27/22; A61L27/24; A61L27/28; A61L27/34; A61L27/40; A61L27/44; A61L31/00; A61L31/04; A61L31/042; A61L31/043; A61L31/044; A61L31/12; A61L31/125; C07; C07K; C07K14/00; C07K14/435; C07K14/475; C07K14/495; C07K14/78; C08B; C08B37/00; C08B37/006; C08B37/0063; C08B37/0069; C08B37/0072; C08L; C08L89/00; C08L89/04; C08L89/06; C09; C09J; C09J189/00; C09J189/04; C09J189/06; G; G02; G02B; G02B1/00; G02B1/04; G02B1/041; G02B1/043; A61F; A61F2/00; A61F2/02; A61F2/04; A61F2/06; A61F2/07; A61F2310/00; A61F2310/00005; A61F2310/00365; A61K38/00; C08L2666/00; C08L2666/02
Claims Analysis
Total Claims: 39
Claim 1
Independent Claim
78 words
A process of preparing a crosslinked biomaterial composition comprising: providing a means for delivering a biocompatible polymer and a means for delivering a sterile, dry crosslinking agent; adequately mixing the biocompatible polymer and the crosslinking agent to initiate crosslinking between the biocompatible polymer and the crosslinking agent; delivering the biocompatible polymer and the crosslinking agent to a destination selected from the following: a mold, a surface of a synthetic implant, and a tissue site in need of augmentation.
Claim 2
Dependent Claim
28 words
The process of claim 1, wherein the biocompatible polymer is selected from the group consisting of collagen, a collagen derivative, a glycosaminoglycan, a glycosaminoglycan derivative, and mixtures thereof.
Claim 3
Dependent Claim
34 words
The process of claim 2, wherein the glycosaminoglycan is selected from the group consisting of: hyaluronic acid, chondroitin sulfate A, chondroitin sulfate C, dermatan sulfate, keratan sulfate, keratosulfate, chitin, chitosan, heparin, and mixtures thereof.
Claim 4
Dependent Claim
25 words
The process of claim 1, wherein the means for delivering the biocompatible polymer and the means for delivering the sterile, dry crosslinking agents are syringes.
Claim 5
Dependent Claim
65 words
A process of augmenting tissue comprising: providing a first syringe containing collagen and a second syringe containing a sterile, dry, synthetic hydrophilic polymer capable of reacting with collagen to provide crosslinking; adequately mixing the collagen and the synthetic hydrophilic polymer to initiate crosslinking between the collagen and the synthetic polymer; injecting the collagen and the synthetic polymer to a tissue site in need of augmentation.
Claim 6
Dependent Claim
14 words
The process of claim 2 or 5, wherein the collagen is atelopeptide fibrillar collagen.
Claim 7
Dependent Claim
23 words
The process of claim 4 or 5, wherein at least one of the syringes has a contraction ratio of about 4.0 or greater.
Claim 8
Dependent Claim
20 words
The process of claim 7, wherein at least one of the syringes has a barrel volume of approximately 3 cm³.
Claim 9
Dependent Claim
36 words
The process of claim 4 or 5, wherein the contents of the first syringe and the contents of the second syringe are mixed using syringe-to-syringe mixing using at least 20 passes of material between the syringes.
Claim 10
Dependent Claim
30 words
The process of claim 4 or 5, wherein the biocompatible polymer and crosslinking agent are injected to a tissue site in need of augmentation through a 25-gauge or smaller needle.
Claim 11
Dependent Claim
24 words
The process of claim 10, wherein the biocompatible polymer and crosslinking agent are injected to the tissue site through a 27-gauge or smaller needle.
Claim 12
Dependent Claim
22 words
The process of claim 11, wherein the biocompatible polymer and crosslinking agent are injected to the tissue site through a 30-gauge needle.
Claim 13
Dependent Claim
18 words
The process of any one of the preceding claims, wherein the tissue site is a soft tissue site.
Claim 14
Dependent Claim
18 words
The process of any one of the preceding claims, wherein the tissue site is a hard tissue site.
Claim 15
Dependent Claim
61 words
A process for preparing a sterile, dry crosslinking agent contained within a syringe comprising the steps of: dissolving a dry crosslinking agent in a fluid carrier to produce a crosslinker solution; sterile-filtering the crosslinker solution to produce a sterile crosslinker solution; dispensing the sterile crosslinker solution into a syringe; and lyophilizing the sterile crosslinker solution within the syringe under aseptic conditions.
Claim 16
Dependent Claim
62 words
A process for preparing a sterile, dry crosslinking agent contained within a syringe comprising the steps of: dissolving a dry crosslinking agent in a fluid carrier to produce a crosslinker solution; dispensing the crosslinker solution into a syringe; lyophilizing the crosslinker solution within the syringe to produce a dry crosslinking agent; and sterilizing the dry crosslinking agent within the syringe using irradiation.
Claim 17
Dependent Claim
63 words
A process for preparing a sterile, dry crosslinking agent contained within a syringe comprising the steps of: dissolving a dry crosslinking agent in a nonaqueous carrier to produce a crosslinker solution; sterile-filtering the crosslinker solution to produce a sterile crosslinker solution; dispensing the sterile crosslinker solution into a syringe; and drying the sterile crosslinker solution within the syringe by evaporation under aseptic conditions.
Claim 18
Dependent Claim
65 words
A process for preparing a sterile, dry crosslinking agent contained within a syringe comprising the steps of: dissolving a dry crosslinking agent in a nonaqueous carrier to produce a crosslinker solution; dispensing the crosslinker solution into a syringe; drying the sterile crosslinker solution within the syringe by evaporation to produce a dry crosslinking agent; and sterilizing the dry crosslinking agent within the syringe using irradiation.
Claim 19
Dependent Claim
33 words
A process for preparing a sterile, dry crosslinking agent contained within a syringe comprising dispensing a dry crosslinking agent into a syringe and sterilizing the dry crosslinking agent within the syringe using irradiation.
Claim 20
Dependent Claim
22 words
The process of claim 19, wherein the dry crosslinking agent is compressed into a mold prior to being dispensed into the syringe.
Claim 21
Dependent Claim
24 words
The process of claim 19, wherein the dry crosslinking agent is mixed with a dry inert agent prior to being dispensed into the syringe.
Claim 22
Dependent Claim
29 words
The process of claim 21, wherein the dry crosslinking agent is mixed with a dry inert agent, then compressed into a mold prior to being dispensed into the syringe.
Claim 23
Dependent Claim
28 words
The process of claim 21, wherein the dry inert agent is selected from the group consisting of polyethylene glycol, a sugar, a salt, a carbohydrate, and mixtures thereof.
Claim 24
Dependent Claim
15 words
The process of claim 23, wherein the dry inert agent is glucose or sodium chloride.
Claim 25
Dependent Claim
26 words
A process for preparing a sterile, dry crosslinking agent comprising molding a dry crosslinking agent to form a pellet and sterilizing the pellet using e-beam irradiation.
Claim 26
Dependent Claim
23 words
The process of any one of claims 1 to 4 and 15 to 25, wherein the crosslinking agent is a synthetic hydrophilic polymer.
Claim 27
Independent Claim
23 words
The method of any one of claims 5 to 14 and 26, wherein the synthetic hydrophilic polymer is a functionally activated polyethylene glycol.
Claim 28
Dependent Claim
17 words
The method of claim 27, wherein the functionally activated polyethylene glycol is a difunctionally activated polyethylene glycol.
Claim 29
Dependent Claim
15 words
The process of claim 15 or 16, wherein the fluid carrier is an aqueous carrier.
Claim 30
Dependent Claim
22 words
The process of claim 29, wherein the aqueous carrier has a pH within the range of between about 3.0 and about 5.0.
Claim 31
Dependent Claim
15 words
The process of claim 15 or 16, wherein the fluid carrier is a nonaqueous carrier.
Claim 32
Dependent Claim
13 words
The process of claim 17 or 18, wherein the nonaqueous carrier is ethanol.
Claim 33
Dependent Claim
26 words
The process of claim 15 or 17, wherein sterile filtration is performed using a filter having pores with a diameter of approximately 0.22 microns or smaller.
Claim 34
Dependent Claim
19 words
The process of claim 16, 18 or 19, wherein the irradiation is selected from e-beam irradiation and gamma irradiations.
Claim 35
Dependent Claim
29 words
The process of claim 17 or 18, wherein drying by evaporation is performed under vacuum at a temperature within the range of about 10 °C to about 20 °C.
Claim 36
Dependent Claim
16 words
The process of claim 25, wherein the pellet is dispensed into a syringe prior to irradiation.
Claim 37
Dependent Claim
21 words
The process of claim 25, wherein the radiation dosage is within the range of about 0.5 Mrad to about 4 Mrad.
Claim 38
Dependent Claim
21 words
The process of claim 36, wherein the e-beam irradiation is within the range of about 1.5 Mrad to about 2.5 Mrad.
Claim 39
Dependent Claim
26 words
An article of manufacture comprising a syringe containing a sterile, dry crosslinking agent prepared according to the process of any one of claims 15 to 19.
References Cited (Backward Citations)
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