Pressure sensitive adhesives with amphiphilic copolymers

Abstract

A silicone pressure sensitive adhesive with amphiphilic copolymers for maintaining adhesion in a moist environment. The amphiphilic copolymers for silicone adhesives include at least one silicone moiety and at least one hydrophilic segment. Such adhesives are applicable to securing medical devices to human skin.

Claims

1. A silicone pressure sensitive adhesive composition suitable for adhering a medical device to skin comprising 0.1-100% of an amphiphilic random copolymer that is a free radical polymerization reaction product of at least one silicone monomer or oligomer and at least one hydrophilic or amphiphilic monomer or oligomer, such that the amphiphilic copolymer: a) does not dissolve in aqueous medium, b) has a molecular weight greater than 10,000 g/mol; and c) does not leach out in the presence of moisture; and wherein the silicone monomer is methacryloylalkylsiloxysilane, vinylalkylsiloxysilane, vinylalkoxysilane, or combinations thereof; the silicone oligomer is polydimethylsiloxane with reactive groups selected from hydride, vinyl, methacrylate, acrylate, epoxy, carbinol, mercapto, acetoxy, amino, isocyanato, halide, hydroxyl, and combinations thereof; and the hydrophilic or amphiphilic monomer or oligomer is selected from acrylamides, N-alkylacrylamides, N,N-dialkylacrylamides, N-alkylaminoalkylacrylamides, methacrylamides, acrylic acid and its esters and salts, methacrylic acid and its esters and salts, amino methacrylates, N-alkylamino acrylates, N-alkylamino methacrylates, maleic anhydride and its derivatives, alkenyl anhdyride and its derivatives, vinyl ethers, reactive polyethers, polyisocyanates, polyesters, polyamides, polypeptides, polysaccharides, polyurethanes, and combinations thereof.

2. An ostomy device comprising a silicone pressure sensitive adhesive composition on a body contacting surface of the device and suitable for adhering the device to the body, wherein the pressure sensitive adhesive comprises an amphiphilic random copolymer that is a free radical polymerization reaction product of at least one silicone monomer or oligomer and at least one hydrophilic or amphiphilic monomer or oligomer such that the amphiphilic copolymer: a) does not dissolve in aqueous medium; and b) has a molecular weight greater than 10,000 g/mol; and wherein the silicone monomer is methacryloylalkylsiloxysilane, vinylalkylsiloxysilane, vinylalkoxysilane, or combinations thereof; the silicone oligomer is polydimethylsiloxane with reactive groups selected from hydride, vinyl, methacrylate, acrylate, epoxy, carbinol, mercapto, acetoxy, amino, isocyanato, halide, hydroxyl, and combinations thereof; the hydrophilic or amphiphilic monomer or oligomer is selected from acrylamides, N-alkylacrylamides, N,N-dialkylacrylamides, N-alkylaminoalkylacrylamides, methacrylamides, acrylic acid and its esters and salts, methacrylic acid and its esters and salts, amino methacrylates, N-alkylamino acrylates, N-alkylamino methacrylates, maleic anhydride and its derivatives, alkenyl anhdyride and its derivatives, vinyl ethers, reactive polyethers, polyisocyanates, polyesters, polyamides, polypeptides, polysaccharides, polyurethanes, and combinations thereof.

3. A wound dressing comprising a silicone pressure sensitive adhesive composition on a body contacting surface of the dressing and suitable for adhering the dressing to the body, wherein the pressure sensitive adhesive comprises an amphiphilic random copolymer which is a free radical polymerization reaction product of at least one silicone monomer or oligomer and at least one hydrophilic or amphiphilic monomer or oligomer such that the amphiphilic copolymer: a) does not dissolve in aqueous medium; and b) has a molecular weight greater than 10,000 g/mol; and wherein the silicone monomer is methacryloylalkylsiloxysilane, vinylalkylsiloxysilane, vinylalkoxysilane, or combinations thereof; the silicone oligomer is polydimethylsiloxane with reactive groups selected from hydride, vinyl, methacrylate, acrylate, epoxy, carbinol, mercapto, acetoxy, amino, isocyanato, halide, hydroxyl, and combinations thereof; the hydrophilic or amphiphilic monomer or oligomer is selected from acrylamides, N-alkylacrylamides, N,N-dialkylacrylamides, N-alkylaminoalkylacrylamides, methacrylamides, acrylic acid and its esters and salts, methacrylic acid and its esters and salts, amino methacrylates, N-alkylamino acrylates, N-alkylamino methacrylates, maleic anhydride and its derivatives, alkenyl anhdyride and its derivatives, vinyl ethers, reactive polyethers, polyisocyanates, polyesters, polyamides, polypeptides, polysaccharides, polyurethanes, and combinations thereof.

4. A securement device for attaching surgical devices, catheters, and intravenous delivery devices to the body comprising a silicone pressure sensitive adhesive composition on a body contacting surface of the device, and suitable for adhering the securement device wherein the pressure sensitive adhesive comprises an amphiphilic random copolymer which is a free radical polymerization reaction product of at least one silicone monomer or oligomer and at least one hydrophilic or amphiphilic monomer or oligomer such that the amphiphilic copolymer: a) does not dissolve in aqueous medium; and b) has a molecular weight greater than 10,000 g/mol; and wherein the silicone monomer is methacryloylalkylsiloxysilane, vinylalkylsiloxysilane, vinylalkoxysilane, or combinations thereof; the silicone oligomer is polydimethylsiloxane with reactive groups selected from hydride, vinyl, methacrylate, acrylate, epoxy, carbinol, mercapto, acetoxy, amino, isocyanato, halide, hydroxyl, and combinations thereof; the hydrophilic or amphiphilic monomer or oligomer is selected from acrylamides, N-alkylacrylamides, N,N-dialkylacrylamides, N-alkylaminoalkylacrylamides, methacrylamides, acrylic acid and its esters and salts, methacrylic acid and its esters and salts, amino methacrylates, N-alkylamino acrylates, N-alkylamino methacrylates, maleic anhydride and its derivatives, alkenyl anhdyride and its derivatives, vinyl ethers, reactive polyethers, polyisocyanates, polyesters, polyamides, polypeptides, polysaccharides, polyurethanes, and combinations thereof.

5. An infusion device comprising a silicone pressure sensitive adhesive composition on a body contacting surface of the device, and suitable for adhering the infusion device to the body, wherein the pressure sensitive adhesive comprises an amphiphilic random copolymer that is a free radical polymerization reaction product of at least one silicone monomer or oligomer and at least one hydrophilic or amphiphilic monomer or oligomer such that the amphiphilic copolymer: a) does not dissolve in aqueous medium; and b) has a molecular weight greater than 10,000 g/mol; and wherein the silicone monomer is methacryloylalkylsiloxysilane, vinylalkylsiloxysilane, vinylalkoxysilane, or combinations thereof; the silicone oligomer is polydimethylsiloxane with reactive groups selected from hydride, vinyl, methacrylate, acrylate, epoxy, carbinol, mercapto, acetoxy, amino, isocyanato, halide, hydroxyl, and combinations thereof; the hydrophilic or amphiphilic monomer or oligomer is selected from acrylamides, N-alkylacrylamides, N,N-dialkylacrylamides, N-alkylaminoalkylacrylamides, methacrylamides, acrylic acid and its esters and salts, methacrylic acid and its esters and salts, amino methacrylates, N-alkylamino acrylates, N-alkylamino methacrylates, maleic anhydride and its derivatives, alkenyl anhdyride and its derivatives, vinyl ethers, reactive polyethers, polyisocyanates, polyesters, polyamides, polypeptides, polysaccharides, polyurethanes, and combinations thereof.

Description

DETAILED DESCRIPTION OF THE INVENTION

(1) The present invention includes silicone pressure sensitive adhesive compositions having novel amphiphilic silicone copolymers. The silicone pressure sensitive adhesive compositions according to the present invention are suitable for adhering to biological surfaces. The pressure sensitive adhesive includes an amphiphilic copolymer that is a reaction product of at least one silicone monomer or oligomer and at least one hydrophilic or amphiphilic monomer or oligomer. such that the amphiphilic copolymer: does not dissolve in aqueous medium, and has a molecular weight greater than 10,000 g/mol

(2) The silicone monomer is a methacryloylalkylsiloxysilane, vinylalkylsiloxysilane, vinylalkoxysilane, and combinations thereof.

(3) The silicone oligomer is polydimethylsiloxane with reactive groups selected from hydride, vinyl, methacrylate, acrylate, epoxy, carbinol, mercapto, acetoxy, amino, isocyanato, halide, hydroxyl, and combinations thereof.

(4) The hydrophilic or amphiphilic monomer or oligomer is selected from acrylamides, N-alkylacrylamides, N,N-dialkylacrylamides, N-alkylaminoalkylacrylamides, methacrylamides, acrylic acid and its esters and salts, methacrylic acid and its esters and salts, amino methacrylates, N-alkylamino acrylates, N-alkylamino methacrylates, maleic anhydride and its derivatives, alkenyl anhdyride and its derivatives, vinyl ethers, reactive polyethers, polyisocyanates, polyesters, polyamides, polypeptides, polysaccharides, polyurethanes, and combinations thereof.

(5) A silicone pressure sensitive adhesive composition as described above is suitable for adhering medical devices to biological surfaces when it comprises 0.1-100% of an amphiphilic copolymer of at least one silicone monomer or oligomer and at least one hydrophilic or amphiphilic monomer or oligomer that does not leach out in the presence of moisture. Such an adhesive is applicable for adhering medical devices, such as ostomy appliances, wound dressings, securement devices for surgical devices, intravenous delivery devices, catheters and infusion devices to human skin.

(6) The amphiphilic copolymer structure is a block, alternating, random, branched, grafted, or a combination.

(7) According to the present invention, a silicone pressure sensitive adhesive is blended with a sufficient amount of amphiphilic silicone copolymer so as to yield an adhesive that stays adhered under moist conditions and will not leach the copolymer in moisture. The invention also includes the synthesis of an amphiphilic silicone copolymer that is a pressure sensitive adhesive by itself.

(8) Amphiphilic Copolymers:

(9) The amphiphilic copolymers are based on a polymerizable silicone monomer copolymerized with hydrophilic and/or amphiphilic monomers.

(10) Synthesis of Amphiphilic Tris(trimethylsiloxysilyl propyl) Methacrylate (TRIS) Copolymers

(11) The typical procedure for the synthesis of the poly(TRIS)-based random copolymers, via free radical polymerization, is as follows, using poly(TRIS-co-N,N-dimethylaminoethyl methacrylate) (DMAEMA) (3:1 wt) as an example: 4.5 g TRIS and 1.5 g of DMAEMA were added into a 25 mL pressure resistant reaction flask. Then 0.045 g VAZO 67 was transferred into the flask. To the flask was then added 14 g ethyl acetate to afford a 30 wt % solution. The mixture was gently shaken until a clear solution was obtained. It was then flushed with nitrogen for 2 minutes, sealed, and let sit in a 65 C. oil bath for 6 hours. Following this, the solvent was evaporated at room temperature for 36 hours to produce a more viscous solution, which was then cast onto polyethylene film and further dried for 2 days, and finally vacuum dried. The copolymer, a soft, tacky solid, was washed in deionized water and H.sub.2O/methanol 50/50 v/v mixture.

(12) Similarly, other TRIS copolymers were made with methacrylic acid (MAA), N-vinylcaprolactam (NVCL), N-isopropylacrylamide (NIPAM), N-hydroxyethylacrylamide (NHEA), and methacrylate-terminated PDMS.

(13) Pressure Sensitive Adhesive Compositions with Amphiphilic Silicone Copolymers

EXAMPLE 1

(14) The typical procedure for the preparation of silicone gel adhesive containing amphiphilic copolymer is as follows. A 1:1 ratio of NUSIL MED-6345 Part A and Part B were taken. Then poly(TRIS-co-NIPAM) (3:1 monomer wt ratio) solution in HMDS was added so that the adhesive gel would eventually contain 5 wt % of solid copolymer. The mixture was thoroughly stirred and then coated on a polyurethane film and allowed to dry for 1 hour for evaporation of solvent. Later the adhesive was cured at 60 C. in the oven for 3 hours. In the case of 100% amphiphilic copolymer, the copolymer was dissolved in HMDS, coated onto to a polyurethane film and then dried in the oven. A 1-inch by 1.5-inch strip of the adhesive was tested on human subject for adhesion under dry and wet environment. For dry adhesion, the tape was secured to the abdominal area for 8 hours prior to removal. For wet adhesion, the tape was attached to abdominal skin of the human subject and then tape removed after an aerobic activity for 40-60 minutes. The results of the adhesion studies under dry and wet conditions are shown in Table 1.

(15) TABLE-US-00001 TABLE 1 No. Sample Description *Dry Adhesion **Wet Adhesion 1 Control: MED 6345 50/50 Parts A/B Adhered well Completely delaminated cured at 60 C. for 3 hr (17-65) 2 MED 6345 50/50 Parts A/B + 5 wt % Adhered well Good adhesion; no Poly(TRIS-co-NIPAM) residue 5 mol % NIPAM Cured at 60 C.3 hr (17-83) 3 Control: MED 6345 30/70 Parts A/B Poor adhesion- Completely delaminated cured at 60 C. for 3 hr (17-65) delaminated completely 4 MED-6345 50/50 Parts A/B + 10 wt Adhered well Weak adhesion; no % Poly(TRIS-co-DMAEMA) residue 5 mol % DMAEMA Cured at 60 C.3 hr (17-83) 5 Poly(TRIS-co-Methacrylic acid) w/5 Adhered very well- Very good adhesion- mol % methacrylic acid cold flow at left a lot of residue edges *Adhesion to abdominal skin for 8 hrs prior to removal (1.5 adhesive strip) **Adhesion to abdominal skin followed by 40-60 minutes of activity prior to removal while perspiring MED-6345 is a two-part tacky silicone gel from NUSIL Technology. VAZO 67 is a free radical initiator from DUPONT.

(16) Adhesives, 2, 4 and 5 are sufficient to secure an ostomy appliance, wound dressing, infusion device or other securement device to human skin.

(17) Other Inventive Examples

(18) The dry adhesion was measured at room temperature with a finger. The range of 0-5 was used (5=excellent adhesion, 0=no adhesion) for qualifying adhesion. The wet adhesive strength was measured using a tongue depressor which had been soaked in water for 5 min (and dipped in water and taken out before each measurement). The polymer films were cast from 20 wt % solutions in ethyl acetate, dried for 5 h, and equilibrated at 35 C. in the incubator overnight in a moist environment, then taken out and immediately measured. (The wet adhesion for all other materials was measured this way unless otherwise mentioned.) The cohesive strength indicates the ability of the adhesive film to be removed from the substrate without leaving residue or breaking apart. Cohesive strength was measured on a scale of 1 to 5 (5=no residue with intact film, 1=low cohesive strength with extensive residue remaining on the host substrate)

(19) TABLE-US-00002 TABLE 2 Properties of blends of MED-6345(50/50) with poly(TRIS/NVCL) Weight Wet Cohesive Formulation Ratio Adhesion Strength MED-6345 (50/50) 100:0 3 1 MED-6345 (50/50) + 100:5 3.5 1 poly(TRIS/NVCL) (3.6/1)

(20) TABLE-US-00003 TABLE 3 Properties of TRIS/MAA polymers (unpurified) Polymer Dry Wet Cohesive (unpurified) adhesions.sup.a adhesion strength TRIS/MAA (97/3) 1/2.5 0 3.5 TRIS/MAA (97.5/2.5) 2.5/3.5 0.5 3.5 TRIS/MAA (98/2) 3/4 0.5 3 TRIS/MAA (98.5/1.5) 3/4 1 2.5 TRIS/MAA (99/1) 4/>5 1.5 1.5 .sup.aadhesion after pressing for ~0.5 seconds/adhesion after pressing for ~10 seconds

(21) TABLE-US-00004 TABLE 4 Properties of TRIS/MAA polymers (unpurified, heated at 60 C. overnight) Polymer Dry Wet Cohesive (unpurified) adhesions.sup.a adhesion strength TRIS/MAA (97/3) 0/0.5 0 5 TRIS/MAA (97.5/2.5) 0.5/1 0 4.5 TRIS/MAA (98/2) 1/2 0 4 TRIS/MAA (98.5/1.5) 1.5/2.5 0.5 4 TRIS/MAA (99/1) 3/3.5 1 3.5 .sup.aadhesion after pressing for ~0.5 seconds/adhesion after pressing for ~10 seconds

(22) TABLE-US-00005 TABLE 5 Properties of TRIS/MAA polymers (purified, not heated) Polymer Dry Wet Cohesive (purified) adhesions.sup.a adhesion strength TRIS/MAA (97/3) 0/0 0 5 (brittle) TRIS/MAA (97.5/2.5) 0/0 0 5 (brittle) TRIS/MAA (98/2)10 mol % MAA 0/0 0 5 (almost brittle) TRIS/MAA (98.5/1.5) 0/0.5 0 5 TRIS/MAA (99/1)5 mol % MAA 1/1.5 0 4.5 TRIS/MAA (99.5/0.5) 1.5/2 0 4 TRIS/MAA (99.75/0.25) 1.5/2.5 0.5 4 TRIS/MAA (99.875/0.125) 2/3 0.5 3.5 TRIS/MAA (99.9375/0.0625) 3/3.5 1 2.5 TRIS (100%) 3.5/5 1 1.5 .sup.aadhesion after pressing for ~0.5 seconds/adhesion after pressing for ~10 seconds

(23) TABLE-US-00006 TABLE 6 Properties of purified TRIS/NIPAM copolymers Polymer Dry Wet Cohesive (purified) adhesions.sup.a adhesion strength TRIS/NIPAM (5/1) 0/0 0 5 (brittle) TRIS/NIPAM (6/1) 0/0.5 0 5 (almost brittle) TRIS/NIPAM (7/1) 0.5/1.5 0 5 TRIS/NIPAM (8/1) 1/2 0 5 TRIS/NIPAM (12/1) 1/2.5 0 5 TRIS/NIPAM (15/1) 1.5/3 0 4.5

(24) TABLE-US-00007 TABLE 7 Properties of NIPAM/PDMS-macromonomer copolymers Dry Wet Cohesive Polymer adhesions.sup.a adhesion strength NIPAM/PDMS- 0/0.5 0 5 (slightly rubbery) macromonomer (1/2.5) NIPAM/PDMS- 0/0.5 0 4.5 (somewhat rubbery) macromonomer (1/3) NIPAM/PDMS- 3/4.5 1 1 (rubbery but weak) macromonomer (1/5) NIPAM/PDMS- N/A N/A 0 macromonomer (1/7) NIPAM/PDMS- N/A N/A 0 macromonomer (1/10) PDMS-macromonomer purchased from GELEST, Inc.

(25) We believe that this is the first time that a unique amphiphilic silicone copolymer has been synthesized that is used in a pressure sensitive adhesive composition and is capable of securely adhering medical devices to the body.

(26) Tables 1-7 indicate that the pressure sensitive adhesives with amphiphilic copolymers of the present invention adhere well under dry and wet conditions. Furthermore, adhesion of these compositions to skin shows an improvement over silicone adhesives without the copolymers.