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US5407445.Pdf ||||||||||||||||| USOO5407445A United States Patent (19) 11 Patent Number: 5,407,445 Tautvydas et al. 45 Date of Patent: Apr. 18, 1995 54 GEL COMPOSITION FOR IMPLANT 4,790,848 12/1988 Cronin . PROSTHESIS AND METHOD OF USE 4,795,463 1/1989 Gerow . 4,820,302 4/1989 Woodroof. 75 Inventors: Daiva K. Tautvydas, Atlanta; 4,820,303 4/1989 Brauman . Mannarsamy Balasubramanian, 4,822,741 4/1989 Bares . Roswell; R. Martin Emanuele, 4,828,561 5/1989 Woodroff. Alpharetta, all of Ga. 4,839,280 6/1989 Bares . 73 Assignee: Cytrk Corporation, Norcross, Ga. s: $3. kistan. 21 Appl. No.: 64,519 4,912,141 3/1990 Kronman , 4,936,858 6/1990 O'Keeffe . 22 Filed: May 19, 1993 4,955,909 9/1990 Ersek et al. 4,963,150 10/1990 Brauman . Related U.S. Application Data 4,995,882 2/1991. Destouet et al. a 5,019, 100 5/1991 Hennink et al. (63) in part of Ser. No. 886,264, May 20, 5,067,965 11/1991 Ersek et al. s 5,120,816 6/1992 Gould et al. 51) Int. Cl. ................................................ A61F 2/12 52 U.S. C. .......................................... 623/8; 623/11; OTHER PUBLICATIONS 623/66 Touchette, N., “Research. In Focus-Silicone Implants 58 Field of Search ............... 623/11, 16, 66; 528/76; and Autoimmune Disease: Studies Fail to Gel, The 424/422 Journal of NIH Research, vol. 4, pp.49-52 (May 1992). Gladwell, M., “FDA Wii Allow Limited Use of 56 References Cited Silicone-Gel Breast Implants', the Washington Post, U.S. PATENT DOCUMENTS Section A, Final Edition, p. 902 (Apr. 17, 1992). Goin, J., “High-Pressure Injection of Silicone Gel Into E. 1225 SA al. An Axilla-A Complication of Closed Compression 3,681,787 8/1972 Perras . Capsulotomy Of The Breast,” Plastic & Reconstructive 3,683,424 8/1972 Pangman. Surgery, vol. 62, No. 6, pp. 891-895 (Dec, 1978). 3,919,724 11/1975 Sanders et al. Spancake, C. et al., “Thermorheologic Properties of 4,095,295 6/1978 Lake . Aqueous Sol and Gels of Tetronic 1508, Pharmaceuti 4,143,428 3/1979 Cohen . cal Research, vol. 8, No. 3, pp. 345-349 (1991). 4,298,997 11/1981 Rybka . Lenaerts, V., “Temperature-dependent rheological 4,298,998 11/1981 Naficy . behaviour of Pluronic F-126 aqueous solutions, Int, 4,433,440 2/1984 Cohen . Journal of Pharm., vol. 39, pp. 121-127 (1987). 4,507,810 4/1985 Bartholdson . 4,573,999 3/1986 Netto . Primary Examiner-David Isabelia 4,610,690 9/1986 Tiffany . Attorney, Agent, or Firm-Jones & Askew 4,636,213 1/1987 Pakian . 4,648,880 3/1987 Brauman . 57 ABSTRACT 4,650,487 3/1987 Chaglassian . In accordance with the present invention, a composi 4,657,553 4/1987 Taylor . tion and method is provided for a biocompatible filler 4,702,917 10/1987 Schinder . for prostheses. The composition and method relate to 4,713,073 12/1987 Reinmuller . certain polyoxyethylene/polyoxypropylene block co 4,731,081 3/1988 Tiffany et al. 4,740,208 4/1988 Cavon . polymers which have gelling properties at body tem 4,769,036 9/1988 Moder . perature and are ideally suited for use as fillers for a soft 4,772.284 9/1988 Jefferies et al. tissue prosthesis such as a breast implant. 4,772,285 9/1988 Ksander et al. 4,773,909 9/1988 Chaglassian . 16 Claims, 10 Drawing Sheets Typical Test Curve (Sample 14 at 37C) so inverse Exponential Relaxation O 20 40 s SO U.S. Patent Apr. 18, 1995 Sheet 1 of 10 5,407,445 ?TAZZAZZI 00€ 09% 00% 0SI 001 (3) goo U.S. Patent Apr. 18, 1995 Sheet 2 of 10 5,407,445 Effect of Polymer Concentration on Peak Force 17% POLOX (Room Temperature) 18.5% POLOx Z 20% POLOX Effect of Polymer Concentration on Peak Force 23.5% POLOX (Room Temperature) 25% POLOx 26.5% POLOX 1% Salt U.S. Patent 5,407,445 N. U.S. Patent Apr. 18, 1995 sheet 4 of 10 5,407,445 Effect of Salt Concentration on Peak Force (Room Temperature) 122: 17% POLOX 18.5% POLOX 20% POLOX Effect of Salt Concentration on Peak Force (Room Temperature) 22 25% POLOX 26.5% POLOX POLOXAMER. 338 U.S. Patent Apr. 18, 1995 Sheet 5 of 10 5,407,445 Effect of Salt Concentration on Peak Force (37C) 17% POLOX 18.5% POLOX 20% POLOX Effect of Salt Concentration on Peak Force (37C) 23.5% POLOX 25% POLOX 26.5% POLOX POLOXAMER 338 U.S. Patent Apr. 18, 1995 Sheet 6 of 10 5,407,445 Effect of Temperature Room Temperature on Peak Force 37 degrees Celcius SAMPLE SAMPLE SAMPLE SAMPLE SAMPLE SAMPLE 16 Effect of Temperature Room Temperature on Peak Force 37 degrees Celcius 2 00 100 19% SALT SAMPLES U.S. Patent Apr. 18, 1995 Sheet of 10 5.407 445 59 g U.S. Patent Apr. 18, 1995 Sheet 8 of 10 5,407,445 Relaxation as a Function of Composition 2 e w en w) es s S w es 9 24 s MEAN MEAN MEAN MEAN MEAN MEAN 407. 407- 47- 338- 338- 338 17% 18.5% 20% 23.5% 25% 26.5% Z–7A77 13 Relaxation as a Function of Composition MEAN MEAN MEAN MEAN MEAN MEAN 40- 40- 407- 338- 338- 338 179. 18.5% 20% 23.5% 25% 26.5% 7A71Az-14 U.S. Patent Apr. 18, 1995 Sheet 9 of 10 5,407,445 Effect of Temperature Room Temperature on Relaxation D 37 degrees Celcius 100.00% 80.00% 60.00% 40.00% 20.00% 0.00% SAMPLE SAMPLE SAMPLE SAMPLE SAMPLE SAMPLE 4. 7 10 13 16 0% SALT SAMPLES Effect of Temperature Room Temperature on Relaxation 37 di Celicius 80.00% 60.00% 40.00% 20.00% 0.00% SAMPLE SAMPLE SAMPLE SAMPLE SAMPLE SAMPLE 3 6 9 12 15 1. 1% SALT SAMPLES zz7-7A776 to U.S. Patent Apr. 18, 1995 Sheet 10 of 10 5,407,445 Effect of Temperature Room Temperature on Relaxation 37 degrees Celcius SAMPLE SAMPLE SAMPLE SAMPLE SAMPLE SAMPLE 1 4 7 10 3. 16 0% SALT SAMPLES A7727- 17 Effect of Temperature Room Temperature on Relaxation 37 Cecius SAMPLE SAMPLE SAMPLE SAMPLE SAMPLE SAMPLE 3 6 9 12 1S 8 1% SALT SAMPLES 5,407,445 1. 2 approximate the consistency and appearance of the GEL COMPOSTION FOR IMPLANT human breast and to avoid the negative biological af. PROSTHESIS AND METHOD OF USE fects associated with introducing a foreign structure into the body. CROSS-REFERENCE TO RELATED 5 For example, U.S. Pat. No. 4,573,999 to Netto de APPLICATIONS scribes a prosthetic implant for human breasts wherein This is a continuation-in-part patent application of the exterior surface of the lumen has concentric waves U.S. patent application Ser. No. 07/886,264, filed on which serve to relieve the pressure caused by capsular May 20, 1992, now abandoned. contracture without reducing the volume or firmness of O the implant. U.S. Pat. No. 4,790,848 describes a multiple TECHNICAL FIELD lumen breast prosthesis in which the innermost lunen is The present invention relates to a biocompatible gel spherical and free-floating to better approximate the composition for use in implantable prostheses. More natural movement of breast tissue. U.S. Pat. No. particularly, the present invention relates to certain 4,650,487 to Chaylassian describes a multilumen breast polyoxyethylene/polyoxypropylene block copolymers 5 lo prosthesis in which the lumens are filled with various which have gelling properties that make them ideally substances to allow adjustment of the volume of the suited for use as fillers for a soft tissue prosthesis such as prosthesis. a breast implant. The various lunens currently used are subject to a BACKGROUND OF THE INVENTION variety of mechanical breakdowns. For example, shell breakdown and rupture often occurs when the filler is a As used herein, the term “prosthesis' means any poor lubricant. This type of bag wall failure is known as device that is implanted into the body of a human or "fold flaw.' Several theories have been advanced to animal to replace or supplement a body part. The term explain why the lumen ruptures. Fold flaw has been 'soft tissue' refers to pliable, soft biological tissues such attributed to the stress differential between the inner as muscie, fat and skin. 25 Implantable prostheses for correcting contour defects and outer surfaces of a bag wall section and a creased and form limitations in the human body have been in use area caused by one wall surface being in compression since at least the early 1950's. The procedure has been and the other being in tension. Fold flaw has also been frequently used for breast reconstruction, either follow attributed to friction between the opposing walls and ing traumatic injury or surgical loss of the breast tissue, changes in the physical properties of the lumen over a as through radical mastectomy, or to correct develop prolonged period of maintaining a crease. In any case, mental hypoplasia. The procedure has also been used mechanical failure of the unen results in introduction for cosmetic breast augmentation. Although the compo of the interior substances into the body cavity. sition of the present invention can be used for recon Shell rupture and breakdown can also occur by exte struction of any soft tissues, the discussion which foll 35 rior mechanical manipulation of the breast. Such manip lows is directed to reconstruction and augmentation of ulation is sometimes necessary to rupture the capsule the breast tissue.
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