STEPHENS DINAH (US)
| WO2000056812A1 | 2000-09-28 |
| EP1004621A1 | 2000-05-31 | |||
| EP0345662A1 | 1989-12-13 | |||
| EP0384110A1 | 1990-08-29 |
| 1. | A method of preparing a sterile article comprising (A) producing a polymer selected from the group consisting of poly (vinyl chloride), poly (vinylidene chloride), polyethylene, and polypropylene, that contains about 0.005 to about 70 phr of a stabiliser having the general formula: where each A is independently selected from E, OR, SR and CO R, and can join the aromatic ring to form an additional ring, E is R or R (OCH2R"CH) n, G is E, COR,C (E) HOR, C (OE) (H)O R,C (E) R") R"'OR,C (E) (R")R'"COOR, C (OE) (R")E"' COOR,C (OE) R'"OR, C (OE) HR, orC (OE) R2, J is A, each R is independently selected from H, R', R"'OR', R"'COOR', R"'C (OR") R", or R'"C (OR") R'"OR", each R'is independently selected from alkyl from Cl to C24 alkaryl from C7 to C24, and aralkyl from C7 to C24, R"is H or R', R"is alkylene from Cl to C24, arylene from C6 to C24 alkarylene from C7 to C24, or aralkylene from C7 to C24, m is 1 to 7, and n is 1 to 20; (B) making said article from said polymer, and (C) sterilising said article with ionising radiation. |
| 2. | A method according to Claim 1 wherein said polymer comprises poly (vinylchloride). |
| 3. | A method according to Claim 1 or 2 wherein A is H. |
| 4. | A method according to Claim 1, 2 or 3 wherein G is H or benzyl. |
| 5. | A method according to any one of Claims 1 to 4 wherein J is R, OR, or SR. |
| 6. | A method according to any one of claims 1 to 5 wherein R is alkyl from C7 to C24. |
| 7. | A method according to any one of Claims 1 to 6 wherein said stabiliser has the general formula. |
| 8. | A method according to any one of Claims 1 to 6 wherein said stabiliser has the general formula. |
| 9. | A method according to any one of Claims 1 to 6 wherein said stabiliser has the general formula. |
| 10. | A method according to any one of Claims 1 to 6 wherein said stabiliser has the general formula. |
| 11. | A method according to any one of Claims 1 to 6 wherein said stabiliser has the general formula. |
| 12. | A sterile article prepared according to the method of any one of Claims 1 to 11. |
| 13. | A method preparing a sterile article comprising (A) making poly (vinyl chloride) that contains about 0.2 to about 20 phr of a stabiliser having the general formula where G is H or benzyl and J is R, OR, or SR, and R is alkyl from C7to C24 (B) making said article from said poly (vinyl chloride), and (C) sterilising said article with gamma radiation. |
| 14. | A method according to Claim 13 wherein said stabiliser has the formula I. |
| 15. | A method according to Claim 13 wherein said stabiliser has the general formula. |
| 16. | A method according to Claim 13 wherein said stabiliser has the general formula. |
| 17. | A method according to Claim 13 wherein said stabiliser has the general formula. |
| 18. | A method according to Claim 13 wherein said stabiliser has the general formula. |
| 19. | A sterile medical article prepared according to the method of any one of Claims 13 to 18. |
| 20. | A method of preparing a sterile medical article comprising (A) making poly (vinyl chloride) that contains about 0.2 to about 20 wt % of a stabiliser having the general formula where G is H or benzyl and each R is independently selected from alkyl from C8 to C12, (B) making said medical article from said poly (vinyl chloride), and (C) sterilising said medical article with gamma radiation. |
| 21. | A resin comprising (A) a polymer selected from the group consisting of poly (vinyl chloride), poly (vinylidene chloride), polyethylene and polypropylene that contains about 0.005 to about 70 phr of a stabiliser having the general formula where each A is independently selected from E, OR, SR, and CO R, and can join the aromatic ring to form an additional ring, E is R or R (OCH2R"CH) n, G is E, COR,C (E) HOR, C (OE) (H)O R,C (E) (R") R"'OR,C (E) (R")R"'COOR, C (OE) (R")E"' COOR,C (OE) R"'OR,C (OE) HR, orC (OE) R2, J is A, each R is independently selected from H, R', R"'OR', R"'COOR', R"'C (OR") R", or R"'C (OR") R"'OR", each R'is independently selected from alkyl from C1 to C24, aryl from C6 to C24, and alkaryl from C7 to C24, R"is H or R', R"'is alkylene from Ci to C24, arylene from C6 to C24, alkarylene from C7 to C24, or aralkylene from C7 to C24, m is 1 to 7, and n is 1 to 20. |
| 22. | A stabiliser for use in stabilising a polymer, the stabliser having the general formula where each A is independently selected from E, OR, SR and CO R, and can join the aromatic ring to form an additional ring, E is R or R (OCH2R"CH)n, G is E, COR,C (E) HOR, C (OE) (H)O R,C (E) R") R"'OR,C (E) (R")COOR, C (OE) (R")E"' COOR,C (OE) R"'OR,C (OE) HR, orC (OE) R2, J is A, each R is independently selected from H, R', R'"OR', R'"COOR', R"'C (OR") R", or R'"C (OR") R'"OR", each R'is independently selected from alkyl from Cl to C24 aryl from C6 to C24, and arlkyl from C7 to C24, R"is H or R', R"is alkylene from C1 to C24, arylene from C6 to C24, alkarylene from C7 to C24 or aralkylene from C7 to C24, m is 1 to 7, and n is 1 to 20;. |
Various polymers, including PVC, polyethylene, and polypropylene, are used to make medical devices and as packaging for food. Sterilization is required and can be accomplished by exposing the devices or packages to gamma radiation.
However, the gamma radiation can degrade the polymers, making them unsuitable or less acceptable for certain applications. In the case of PVC, the yellowing of sterilized articles is the most notable physical change as the result of such degradation.
Benzyl alcohol, geraniol, and some of the related ethers were reported to enhance or help enhance the thermal stability of PVC. (L L. Wood GB 1151108, CAN 71: 92299 ; J. D. Collins, H. Coates, I. H. Siddiqui US 3, 845, 017, JP 55069609 CAN 93: 151163). Benzyl alcohol and cinnamyl alcohol have also been used as solvents for biocides in PVC. (EP 168949 CAN 104: 187573)
Summary of the Invention I have discovered that when certain compounds based on benzyl alcohol, cinnamyl alcohol, or geraniol are incorporated into certain polymers and the polymers are made into articles and are sterilizedwith gamma radiation, substantially less yellowing occurs.
Most of the stabilizers used in this invention are FDA approved additives for food use and could be used for food and medical applications.
Description of the Preferred Embodiments The stabilizers used in this invention have the general formula :
where each A is independently selected from E, OR, SR, and CO-R, and can join the aromatic ring to form an additional ring (e. g., a-hydroxyxanthene), E is R or R (OCH2R"CH)n, G is E, CO-R,-C (E) H-O-R, C (OE) (H)-O-R,-C (E) (R") R"'-OR,- C (E) (R")-R'"-CO-OR, C (OE) (R")-E"'-COOR,-C (OE) R"'-O-R,-C (OE) HR, or-C (OE) R2, J is A, each R is independently selected from H, R', R"'OR', R'"COOR', R"'C (OR") R", or R'"C(OR")R'"OR", each R'is independently selected from alkyl from C, to C24, aryl from C6 to C24, alkaryl from C7 to C24, and aralkyl from ¬7 to C24, R"is H or R', R'" is alkylene from C, to C24, arylene from Cg to C24, alkarylene from C7 to C24, or aralkylene from C ? to C24, m is 1 to 7, and n is 1 to 20. Preferably, A is H and J is R, OR, or SR as those stabilizers are easier to make and more effective. Also, R is preferably alkyl from C7 to C24, R'is preferably alkyl from C, to C, 2, R"is preferably alkyl from C, to C6, R"'is preferably alkyl from C, to C6, G is preferably H or benzyl, and m is preferably 1 for the same reasons. The preferred stabilizers are general formulas (A) and (C) as they are easier to make and less expensive. Example of stabilizers of formula (A) include 4-benzyloxybenzyl alcohol, benzhydrol, 9,10- dihydro-9-anthracenol, 9-hydroxyxanthene, 9H-thioxanthen-9-ol, 1. 2,3,4-tetrahydro- 1-naphthalenol, benzyl ether diveratryl ether, benzyl methoxyethyl acetal, (1R)- (-)- nopol benzyl ether, 1, 3-dibenzyloxy-2-propanol, benzyl benzoate, benzyl acetoacetate, benzyl phenylacetate, dibenzyl adipate, dibenzyl malonate, dibenzyl sebacate, benzyl butyl phthalate, poly(vinyl benzyl ether), poly(benzyl methacrylate), poly (methyl 4-benzyloxy-phenylsiloxane); Example of stabilizers of formula (B) include 1-naphthalenemethanol. 2-naphthalenementhanol, 1-
[ (phenylmethoxy) methyl] naphthalene, 2- [ (phenylmethoxy)-methyl] naphthalene, 1, 1'- [oxybis (methylene)]-bis-naphthalene, 2,2'-[oxybis (methylene)]-bisnaphthalene, 1- naphthylmethyl acetate ; Example of stabilizers of formula (C) include cinnamyl alcohol,-amyl cinnamyl alcohol, trans-2-methyl-3-phenyl-2-propen-1-ol, cinnamyl ether, benzyl cinnamyl ether, cinnamyl acetate, trans-cinnamyl butyrate, cinnamyl benzoate, cinnamyl phenylacetate. cinnamyl isovalerate, cinnamyl acid cinnamyf ester, poly (vinyl cinnamyl ether), poly (cinnamyl methacrylate), poly (methyl 4- cinnamyloxy-phenylsifoxane) ; Example of stabilizers of formula (D) include 3-(1- <BR> <BR> <BR> naphthyl)-2^propen-1-oll 3-(2-naphthyl)-2-propen-1-ol, 3-(1-naphthalenyl)-2-propen- 1-ol acetate, 3-(2-naphthalenyl)-2-propen-1-ol acetate; Example of stabilizers of formula (E) include geraniol, benzyl geranyl ether, geranyl hexanoate, geranyl phenylacetate, poly(vinyl geranyl ether), poly(geranyl methacrylate), poly(methyl 4- geranyloxy-phenylsiloxane).
Some of the stabilizers are commercially available as food additives. Those that are not commercially available can be made by techniques known in the art. For example, cinnamyl benzyl ether can be made by the benzylation of cinnamyl alcohol with benzyl chloride or benzyl bromide in the presence of a base.
The stabilizers of this invention are effective in reducing the yellowing of articles madefrom polymers such as PVC, polyvinylidene chloride, polyethylene, and polypropylene after exposure to ionizing radiation. The polymer can be made into any type of article, including medical devices, food packaging, and radiation protection devices.
The polymer can be stabilized by the addition of about 0.005 to about 70 phr (parts by weight per 100 part by weight of the polymer) of the stabilizer to the polymer. Less stabilizer is less effective and more stabilizer offers little additional benefit. The preferred amount of stabilizer is about 0. 2 to about 20 phr. The stabilizer can be added to a polymer in a variety of ways, such as mixing the reactants at the beginning or during polymerization. The stabilizer is preferably added after at least 70 wt% of the monomer has polymerized. The stabilizer can be added as a solid or with a solvent as a slurry or a solution. Common organic solvents such as N-methylpyrrolidone, diglyme, acetamide, acetone, methanol, ethanol, isopropanol, dimethylsulfoxide, or dimethylformamide can be used ; water can also be used. Water miscible solvents, such as acetone, tetrahydrofuran, and methanol, are preferred. If the stabilizer is a solid, it is preferable to add it in a solvent as that achieves a more uniform distribution of the stabilizer in the polymer.
The stabilizer can also be added to the polymer along with or as a shortstop, or during the drying or compounding of the polymer. Various methods can be used for compounding, including milling, dry mixing, and extrusion.
The following examples further illustrate this invention: EXAMPLES 1 to 125 To a mixture of 150.00 g PVC (sold by Occidental Chemical Corporation as "Oxy 240"or sold by Oxy Vinyls as 30"), 0.30 g stearic acid (used as a lubricant), 0.23 g of a zinc and calcium mixed salts of mixed fatty acids (used as a
heat stabilizer ; sold by Witco as"Mark 152 S"), 97.50g (less the amount of gamma ray stabilizer used) of dioctyl phthalate ("DOP,"used as a plasticizer and to increase flexibility), 15.00 g epoxidized soy bean oil (used as an HCl scavenger to reduce degradation ; sold by Witco as"Drapex 6.8"), was added a gamma ray stabilizer. The mixture was thoroughly blendedandhot milled at 300°F (1 82°C) for 5 minutes. The resulting PVC sheet was cut and pressed into a 4"x3"x1/4" (10x8x0. 6 cm) plaque at 330°F (182°C). The plaque was divided into two smaller pieces. One was saved for comparison and one was subjected to y radiation at a dose of 50 kGy. The irradiated piece was again divided into two pieces and one of these pieces was oven aged at 50"C for 48 hours. All of the samples were measured for yellowness index with a Macbeth 2020 Plus Color Eye Spectrometer, as described by the Hunter equations (see"The Measurement of Appearance"by Richard S. Hunter, John Wiley & Sons, New York, 1975). The following table gives the stabilizers used and the results.
Amount Yellowness Example Stabilizer (g) Initial After After g Control none none 19.1 55. 4 79. 9 1Benzyl ether0. 516. 2 42.9 65.1 2 1.0 17.0 37. 0 57.2 Control none none 21. 1 57.2 77.2 3 Benzyl ether 2. 01 32. 8 33. 1 51.9 4 " 5.02 19.4 26.9 42.4 5 " 10.02 17. 6 22.3 36. 5 6 " 15.04 15.6 19.7 32.2 720. 0316. 1 18. 8 31 8 " 30.02 15.4 17. 3 27-5 Control none none 17-1 52.3 84.4 9 benzyl methoxyethyl acetal 0.5 17.9 42.1 66.1 10 1 02 16. 8 35. 1 58.9 11 " 1.5 16.5 34. 6 54. 5
12 " 2.02 15.4 29.7 50.5 13 " 2.52 17.2 27.8 47.8 14 " 3.02 16.5 27.5 45.2 Contro none none 19.3 55.7 75. 4 15 Diveratryl ether 1.30 19.2 39.8 59. 7 163. 5020. 633. 250. 8 17 Benzyl cinnamyl ether 2.00 18.9 35.8 47. 9 18 " 4.00 17.1 30.5 37.8 19 " 6.00 16.1 27.4 36. 4 Control none none 19. 1 55. 4 79. 9 20 1R)-(-)-Nopol benzyl ether 6.46 19.3 38.6 54. 7 2112. 9216. 734. 847. 0 Control none none 19.1 55.4 79.9 22 1,3-Dibenzyloxy-2-propanol 0.51 17.5 49.3 70.7 23 " 1.02 16.6 44.4 64.3 24 " 1.54 17.5 42.8 62. 4 252. 0317. 439. 860. 3 Control none none 18.1 50.2 75. 5 26 4-Benzyloxybenzyl alcohol 2.40 18.6 28.4 42. 1 274. 8018. 125. 534. 7 Control none none 19. 1 1 55. 4 79. 9 28 9-Hydroxyxanthene 0.50 17.1 62.9 84.2 29 " 1.00 18.4 51.4 72. 7 30 " 1.52 17.3 46.7 68. 4 312. 1717. 7 42.2 63.7 Control none none 21.1 57.2 77.2 32 Benzyl benzoate 2.01 18.6 45.7 65. 3 33 " 5.1 19.0 39.7 58.5 3410. 0118. 734. 351. 8 3515. 0318. 129. 947. 2 3620. 1918. 931. 750. 5 37 " 30.08 19.1 28.3 43.8 Control none none 19.1 55.4 79.9 38 benzyl acetoacetate 4.88 17.9 34.1 46.1 39 " 9.72 23.0 31.0 42. 4 Control none none 21.1 57.2 77. 2 40 Dibenzyl malonate 2. 70 16. 9 29. 4 45. 3 41 " 6.43 17.8 30.8 48.6 Control none none 19.3 55.7 75. 4 42 Dibenzyl sebacate 3.05 18.8 39.9 59. 4 43 " 6.06 18.5 34.2 52. 1 449. 0817. 733. 148. 8 Control none none 19.3 55.7 75. 4
45 Dibe 1 àdi ate 3 00 18 0 40. 0 58 3 466. 0117. 935. 352. 8 479. 0221. 132. 047. 8 Control none none 19. 3 55. 7 75 A 48 Benzyl buiyl phthalate 10. 03 18. 0 40. 2 60. 7 49 "20_03 18. 1 35. 8 53. 7 50 _ 30. 05 18. 8 32 5 48. 3 51 cc 40. 04 18. 5 32. 0 46, 6 5250. 0218. 730. 645. 0 5360. 0620. 129. 243. 6 Control none none 17. 1 52. 3.84.4 54 Dibepal phthalate 1. 50 17. 7 54. 3 55"4_29 15_0 47. 7 Control/U none _ 17. 1 52, 3 84 4 56 Cinnamyl alcohol 8... 571. 1114. 727. 648. 4 58 1. 53--17. 2 27. 5 42. 8 592. 0315. 521. 935. 9 602. 616. 923. 634. 7 613. 0914. 620. 031. 5 Control none none 17-1 52-3 84. 4 62 A1 ha-am 1 cirnam 1 alcohol 0.5118. 756. 977.3 631. 0118. 057. 177. 1 641. 517. 657. 674. 2 2. 01 18. 9 59. 0 74. 7 66 2. 5 19. 3 57. 7 72. 8 3. 02 18. 9 57. 2 70. 0 Control none none 16. 9 61. 7 84. 1 68 T'rans-2-methyl-3-phenyl-2-propen-1_01 17. 334. 8 55. 4 I-ol 2_00 14. 4 27. 8 44_0 3. 00 16. 3 24. 2 37. 8 Control none none 19. 3 55. 7 75. 4 71 Cinnamyl ether _1. 0205 19 7 44. 1 55. 9 722. 041220. 737. 146. 4 73.063718. 833. 141-9 745. 100718. 829. 036. 3 758. 164218-229. 237. 3. Control none none 193 55. 7 75. 4 76 Cinnamy ! aceiate S 7730 19_3 36. 8 Sl_6 Control none none 16. 6 49. I 52, 5 78 Trans-cinnam i butyrate I. 00 18. 2 40, 2 46. 5
79 " 2.02 17.5 35.5 38.7 80 " 3.00 17.4 37.3 37. 5 81 " 4.01 17.0 33.9 38.1 82 " 5.01 16.5 33.2 36.3 83 " 6.02 16.0 32.8 34.3 Control none none 19. 3 61. 6 79. 0 84 Cinnamyl benzoate 3.03 18.8 52.2 64. 4 856. 0018. 544. 056. 5 86 " 9.02 18.6 42.1 52.8 Control none none 19. 3 61. 6 79. 0 87 Cinnamyl phenylacetate 3.01 18.3 43.8 56. 9 88 " 6.02 18.7 39.5 49. 7 89 " 9.04 18.7 36.4 46. 8 Control none none 19. 3 61. 6 79. 0 90 Trans-cinnamyl isovalerate 3.01 18.6 47.6 58.5 1006. 0118. 542. 752. 6 101 " 9.01 18.7 39.6 49.1 Control none none 19. 3 55. 7 75. 4 102 Cinnamic acid cinnamyl ester 3.03 18.7 42.6 52. 0 1036. 0419. 338. 345. 9 104 " 9.05 19.3 35.9 45.1 Control none none 14.9 54.0 74. 7 105 Geraniol 0. 49 14 2 48. 1 67. 5 106 " 0.99 15.0 37.7 56. 6 107 " 2.10 14.4 32.9 50. 4 108 " 2.99 15.1 31.2 45. 1 Control none none 17.1 52.3 84. 4 109 Geranyl hexanoate 0.51 15.6 46.0 72. 0 110 " 1.01 17.5 45.2 73. 3 111 " 1.52 14.8 42.5 70.7 1122. 0218. 642. 267. 8 113 " 2.5 15.2 36.3 66. 2 114 " 3.03 17. 3 37. 9 67. 8 Control none 16. 6 1-5 115 Geranyl benzyl ether 1.03 15.5 36.2 44. 7 1162. 0115. 033335. 1 117 " 3.00 14.2 26.7 33.2 118 " 4.00 14.2 26.1 33. 2 119 " 5.01 14.7 23.4 35.1 120 " 6.04 15.6 25.2 32. 0 Control none none 16. 6 49. 1 52. 5 121 Geranyl phenylacetate 1. 50 18.4 40.5 47. 3 122 " 3.00 15.7 35.1 40.2 123 " 4.50 16.2 29.9 35.5 124 " 6.02 15.3 30.2 37. 3 125 " 7.52 16.0 31.2 33.5
As can be observed from the above table, aftery radiation the polymers that contained a stabilizer had significantly less discoloration than the control samples.
The table also shows that ethers and alcohols are better-at reducing yellowing than esters and can be used in lower 2mounts.