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(12) Patent Application Publication (10) Pub. No.: US 2005/0203635 A1 Hunter Et Al

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(12) Patent Application Publication (10) Pub. No.: US 2005/0203635 A1 Hunter Et Al US 20050203635A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2005/0203635 A1 Hunter et al. (43) Pub. Date: Sep. 15, 2005 (54) SOFT TISSUE IMPLANTS AND application No. 10/986,231, filed on Nov. 10, 2004, ANTI-SCARRING AGENTS and which is a continuation-in-part of application No. 10/986,230, filed on Nov. 10, 2004. (75) Inventors: William L. Hunter, Vancouver (CA); David M. Gravett, Vancouver (CA); (60) Provisional application No. 60/586,861, filed on Jul. Philip M. Toleikis, Vancouver (CA); 9, 2004. Provisional application No. 60/578,471, filed Arpita Maiti, Vancouver (CA) on Jun. 9, 2004. Provisional application No. 60/526, 541, filed on Dec. 3, 2003. Provisional application Correspondence Address: No. 60/525,226, filed on Nov. 24, 2003. Provisional SEED INTELLECTUAL PROPERTY LAW application No. 60/523,908, filed on Nov. 20, 2003. GROUP PLLC Provisional application No. 60/524,023, filed on Nov. 701 FIFTHAVENYUE, SUITE 6300 20, 2003. SEATTLE, WA 98104-7092 (US) Publication Classification (73) Assignee: Angiotech International AG, Zug (CH) (51) Int. Cl. .................................................... A61F 2/02 (21) Appl. No.: 11/006,909 (52) U.S. Cl. .......................................................... 623/23.72 (22) Filed: Dec. 7, 2004 (57) ABSTRACT Related U.S. Application Data Soft tissue implants (e.g., breast, pectoral, chin, facial, lip, and nasal implants) are used in combination with an anti (63) Continuation of application No. 10/996,353, filed on Scarring agent in order to inhibit Scarring that may otherwise Nov. 22, 2004, which is a continuation-in-part of occur when the implant is placed within an animal. Patent Application Publication Sep. 15, 2005 Sheet 1 of 32 US 2005/0203635 A1 N.× ^NJ Patent Application Publication Sep.15, 2005 Sheet 2 of 32 US 2005/0203635 A1 z31.I. loqll 9 Patent Application Publication Sep. 15, 2005 Sheet 3 of 32 US 2005/0203635 A1 Lº 01 Kb8||(Wu)Z801-II Patent Application Publication Sep. 15, 2005 Sheet 4 of 32 US 2005/0203635 A1 N So lEO)oll 9 Patent Application Publication Sep. 15, 2005 Sheet 5 of 32 US 2005/0203635 A1 5 8s SoNS > O Vo loquil 9, Patent Application Publication Sep. 15, 2005 Sheet 6 of 32 US 2005/0203635 A1 Patent Application Publication Sep. 15, 2005 Sheet 7 of 32 US 2005/0203635 A1 s uoqu , Patent Application Publication Sep.15, 2005 Sheet 8 of 32 US 2005/0203635 A1 uOOI|eqKun[u]epou 9(81) pºun?u?up?oueoKu??ue Patent Application Publication Sep.15, 2005 Sheet 9 of 32 US 2005/0203635 A1 Âu|epouu \exiuoolleqn[u] peun?u||ou?uOOp?oueoKu??ue- Patent Application Publication Sep. 15, 2005 Sheet 10 of 32 US 2005/0203635 A1 (?seu?Td06: O?euo6u??eoo?TdOG Patent Application Publication Sep.15, 2005 Sheet 11 of 32 US 2005/0203635 A1 6-dWW £1-68 Patent Application Publication Sep. 15, 2005 Sheet 12 of 32 US 2005/0203635 A1 AP-1 Patent Application Publication Sep. 15, 2005 Sheet 13 of 32 US 2005/0203635 A1 d 9. 5 a Q C9S N h O o SO Xs U NS e Ol3 (-0 x udo) 440Y YO Patent Application Publication Sep. 15, 2005 Sheet 14 of 32 US 2005/0203635 A1 SIROMELYSIN GAPDH Fig. IID Patent Application Publication Sep. 15, 2005 Sheet 15 of 32 US 2005/0203635 A1 ly 290181 IL-1 (ng/ml) - O 20 20 20 20 20 Drug (i) o O 10-7 10-6 10-5 10 Fig. 12A Patent Application Publication Sep. 15, 2005 Sheet 16 of 32 US 2005/0203635 A1 2-Methyl-2,4-Pentanediol (Hexylene Glycol) Collagenase GAPDH IL-1 (ng/ml) O 20 20, 20. Drug (M) O. O. 107 10 10° 10' Fig. 12B Patent Application Publication Sep. 15, 2005 Sheet 17 of 32 US 2005/0203635 A1 Deuterium. Oxide 99.9atomXD Collegenase . .3: . GAPDH ) s Il-1 (ng/ml) O 20 20 20 20 20 Drug (M) 0 0 10-7 10-6 10-5 10-4 Fig. 12C Patent Application Publication Sep. 15, 2005 Sheet 18 of 32 US 2005/0203635 A1 Glycine Ethyl Ester Collagenase is . is. .lar. .. .. * . o, a- t a GAPDH 3. e IL-1 (ng/ml) O 20 20 20 20 20 Drug (M) 0 0 107 10-6 10-5 10-4 Fig. 12D Patent Application Publication Sep. 15, 2005 Sheet 19 of 32 US 2005/0203635 A 1 Ethylene. Glycol. Bis (succinimid Succinole) GAPDH IL-1 (ng/ml) O 20 20 20, 20, 20 Drug (M) 0 0 10-7 10-6 10-5 to 4 Fig. I2E Patent Application Publication Sep. 15, 2005 Sheet 20 of 32 US 2005/0203635 A1 Tubercidin GAPDH O I-1 (ng/ml) O 20 20 20 20 20 Drug (M) o O O-7 10-6 10-5 10 Fig. I2F Patent Application Publication Sep. 15, 2005 Sheet 21 of 32 US 2005/0203635 A1 Aluminum Fluoride Patent Application Publication Sep. 15, 2005 Sheet 22 of 32 US 2005/0203635 A1 Epolhilone B Fig. 12H Patent Application Publication Sep. 15, 2005 Sheet 23 of 32 US 2005/0203635 A1 S. s r yo (d res f UOCUU 9, Patent Application Publication Sep.15, 2005 Sheet 24 of 32 US 2005/0203635 A1 N So loglu Patent Application Publication Sep.15, 2005 Sheet 25 of 32 US 2005/0203635 A1 U E e C r So uoquu% Patent Application Publication Sep.15, 2005 Sheet 26 of 32 US 2005/0203635 A1 o E E res r o Cu) O3Cl. Patent Application Publication Sep. 15, 2005 Sheet 27 of 32 US 2005/0203635 A1 9. s s O 9. As w LO Patent Application Publication Sep.15, 2005 Sheet 28 of 32 US 2005/0203635 A1 '81-I?I Patent Application Publication Sep. 15, 2005 Sheet 29 of 32 US 2005/0203635 A1 a V SN N Sp s w O O Co o O o O C C C C Co oa vo w n co oq va ni C. c. ym ps s yu C c C co O Patent Application Publication Sep. 15, 2005 Sheet 30 of 32 US 2005/0203635 A1 m S. r CD A Q en So R CD A Y M P Patent Application Publication Sep. 15, 2005 Sheet 31 of 32 US 2005/0203635 A1 d e O O N4 'z 69 C e 3. N SOO w e Z. P al pa O r O O Patent Application Publication Sep.15, 2005 Sheet 32 of 32 US 2005/0203635 A1 m | i s i s s s s (uu) e3.IV US 2005/0203635 A1 Sep. 15, 2005 SOFT TISSUE IMPLANTS AND ANTI-SCARRING a biological cascade that ultimately leads to exceSS Scar AGENTS tissue formation. Similarly, if the implant initiates a foreign body response, the Surrounding tissue can be Inadvertently CROSS-REFERENCES TO RELATED damaged from the resulting inflammation, leading to loSS of APPLICATIONS function, tissue damage and/or tissue necrosis. Furthermore, 0001. This application is a Continuation of co-pending certain types of implantable prostheses (Such as breast U.S. application Ser. No. 10/996,353, filed Nov. 22, 2004; implants) include gel fillers (e.g., Silicone) that tend to leak which application is a Continuation-in-part of U.S. applica through the membrane envelope of the Implant and can tion Ser. No. 10/986,231, filed Nov. 10, 2004; and Ser. No. potentially cause a chronic inflammatory response in the 10/986,230, filed Nov. 10, 2004; which application also Surrounding tissue (which augments tissue encapsulation claims the benefit under 35 U.S.C. 119(e) of U.S. Provi and contracture formation). When Scarring occurs around sional Application Ser. Nos. 60/586,861, filed Jul. 9, 2004; the implanted device, the characteristics of the implant No. 60/578,471, filed Jun. 9, 2004; 60/526,541, filed Dec. 3, tissue interface degrade, the Subcutaneous tissue can harden 2003; 60/525,226, filed Nov. 24, 2003; 60/523,908, filed and contract and the device can become disfigured. The Nov. 20, 2003; and 60/524,023, filed Nov. 20, 2003, which effects of unwanted Scarring in the vicinity of the implant are applications are incorporated herein by reference in their the leading cause of additional Surgeries to correct defects, entireties. break down Scar tissue, or remove the implant. BRIEF SUMMARY OF THE INVENTION BACKGROUND OF THE INVENTION 0008 Briefly stated, the present invention discloses phar 0002) 1. Field of the Invention maceutical agents that inhibit one or more aspects of the 0003. The present invention relates generally to soft production of excessive fibrous (Scar) tissue. In one aspect, tissue implants for use in cosmetic or reconstructive Surgery, the present invention provides compositions for delivery of and more Specifically, to compositions and methods for Selected therapeutic agents via medical implants, as well as preparing and using Such medical implants to make them methods for making and using these implants and devices. resistant to overgrowth by inflammatory, fibrous Scar tissue. Compositions and methods are described for coating Soft tissue implants with drug-delivery compositions Such that 0004 2. Description of the Related Art the pharmaceutical agent is delivered in therapeutic levels 0005 The use of soft tissue implants for cosmetic appli over a period sufficient to prevent the implant from being cations (aesthetic and reconstructive) is common in breast encapsulated in fibrous tissue and to allow normal function augmentation, breast reconstruction after cancer Surgery, of the implant to occur. Alternatively, locally administered craniofacial procedures, reconstruction after trauma, con compositions (e.g., topicals, injectables, liquids, gels, genital craniofacial reconstruction and oculoplastic Surgical sprays, microSpheres, pastes, wafers) containing an inhibitor procedures to name a few.
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