WO2002017973A2

WO2002017973A2 - Preparing sterile articles from certain polymers

Info

Publication number: WO2002017973A2
Application number: PCT/GB2001/003918
Authority: WO
Inventors: Qi Wang
Original assignee: Occidental Chemical Corporation; Stephens, Dinah
Priority date: 2000-09-01
Filing date: 2001-08-31
Publication date: 2002-03-07
Also published as: WO2002017973A3; AU2001284229A1

Abstract

A method of preparing a sterile article is disclosed. An article is prepared from a polymer into which is incorporated a stabilizer 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, 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 C1 to C24, aryl from C6 to C24, alkaryl from C7 to C24, and aralkyl 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. The article is exposed to gamma radiation; it yellows less after irradiation than it otherwise would.

Description

PREPARING STERILE ARTICLES FROM CERTAIN POLYMERS

^: Background of the Invention

This invention relates to the preparation of sterile articles from certain polymers. In particular, it relates to making the articles from poly(vinylchloride) (PVC) that contains a benzyl alcohol, cinnamy! alcohol, or geraniol-based stabilizer, then subjecting the article to ionizing radiation, particularly gamma radiation.

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 yeilowing 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 1 151108,

CAN 71 :92299; J. D. Collins.^'Η. Coates, I. H. Siddiqui US 3,845,017; JP 550S9609

CAN 93:151 63). Benzyl alcohol and cinnamy! 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 sterilized with 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:

(A) (B)

(C) CD)

(E) 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., -hydroxyxantheπe), 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^u)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^,nC(OR^u)R"OR", each R' is independently selected from alkyl from C, to C_24l aryl from C₆ to C₂₄, alkaryl from C₇ to C_24l and aralkyl from C₇ to C₂₄, R" is H or R', R'" is alkylene from C, to C_24l arylene from C₆ to C₂ alkarylene from C₇ to C₂₄, or aralkylene from C₇ 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 C_2Δ, R' is preferably alkyl from C, to C_12l R" is preferably alkyl from C, to C₆, R¹" 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 ethei% 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-naphthaJenemethanol, 2-naphthalenemethanol, 1- [(phenylmethoxy)methyl]naphthaleπe, 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-proρen-1-ol, cinnamyl

ether, benzyl cinnamyl ether, cinnamyl acetate, trans-cinnamyl butyrate, cinnamyl benzoate, cinnamyl phenylacetate, cinnamyl isovalerate, cinnamyl acid cinnamyl ester, poly(vinyl cinnamyl ether), poly(cinnamyl methacrylate), ρoly(methyl 4- cinnamyloxy-phenylsiloxane); Example of stabilizers of formula (D) include 3-(l -

naphthyl)-2-propen-1-ol, 3-(2-naphthyl)-2-proρen-1-ol, 3-(1-naρhthalenyl)-2-proρeπ- 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, po!y(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, polyviπylidene 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 ^uOV 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 HCI scavenger to reduce degradation; sold by Witco as "Drapex 6.8"), was added a gamma ray stabilizer. The mixture was thoroughly blended and hot milled at 300°F (182°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 γ 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. Ail 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.

02/17973

02/17973

2/17973

02/17973

As can be observed from the above table, after γ 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 amounts.

Claims

CLAIMS:

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, CO-R, -C(E)H-0-R, C(0E)(H)-O- R, -C(E)R")R'"-OR, -C(E)(R")-R'"-CO-OR, C(OE)(R")-E'"- COOR, -C(OE)R'"-0-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", OΓ R'"C(OR")R' "OR", each R' is independently selected from alkyl from C to C₂ alkaryl from C₇ to C₂₄, and aralkyl from C₇ to C₂₄, R" is H or R', R" is alkylene from Cj 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

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 l l .

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 C₇ to C₂ .

(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

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.

1. 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, CO-R, -C(E)H-0-R, C(OE)(H)-0- R, -C(E)(R")R' "-OR, -C(E)(R")-R'"-CO-OR, C(OE)(R")-E'"- COOR, -C(OE)R'"-0-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_x to C₂ , aryl from C₆ to C₂ , and alkaryl from C₇ to C₂₄, R" is H or R\ R"' is alkylene from Ci to C₂₄, arylene from C₆ to C₂ , alkarylene from C₇ to C₂₄, or aralkylene from C₇ to C₂ , 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, CO-R, -C(E)H-0-R, C(OE)(H)-0- R, -C(E)R")R"'-OR, -C(E)(R")-CO-OR, C(OE)(R")-E'"- COOR, -C(OE)R'"-0-R, -C(OE)HR, or -C(OE)R₂, J is A, each R is independently selected from H, R', R"'OR\ R' "C00R^', R"'C(OR")R", or R^,"C(OR")R'"OR", each R' is independently selected from alkyl from to C₂ aryl from C₆ to C₂ , and arlkyl from C₇ to C₂₄, R" is H or R', R" is alkylene from to C₂₄, arylene from C₆ to C₂ , alkarylene from C₇ to C₂ or aralkylene from C₇ to C₂ , m is 1 to 7, and n is 1 to 20;

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