IE43534B1 - Thermoelastic polymers including block radial polymers to be used as pharmaceutical sealing and resealing materials - Google Patents

Abstract

1517099 Elastic polymer compositions ABBOTT LABORATORIES 25 Aug 1976 [26 Aug 1975] 35418/76 Headings C3B C3M and C3R Copolymer mixtures having elastic properties comprise (1) 10-90% radial block copolymer of 60-85% butadiene and 40-15% styrene having an average molecular weight of at least 150,000 and (2) 90-10% of a polymeric material selected from elastomeric polyolefins, olefin copolymers and terpolymers, vinyl acetate copolymers, polyether and polyester elastomers, acrylics, thermoplastic epoxies, styrene polymers, polycarbonates, acetal resins, polyamides, vinyl chloride polymers, chlorinated polyethylene and mixtures thereof. Exemplified polymeric materials are chlorinated polyethylene and mixtures thereof with polyether and polyester urethane elastomers. The compositions may be moulded into pharmaceutical sealing components, container closures, syringe plunger sealing rings and syringe bulbs.

Description

This invention relates to thermoplastic copolymer compositions which are useful in molding rubber-like materials for contact with body fluids. More particularly, it relates to a thermoplastic composition which comprises a radial block copolymer of butadiene and styrene which has blended with it one or more additional polymeric materials so as to form a rubberlike composition having a high degree of elasticity and resealability. Such a material is useful for puncturable, reseal units for parenteral administration equipment as well as for containers for materials intended for administration to the body. They may also be used in other rubber applications such as syringe bulbs.

Recently, radial block polymers of the butadienestyrene type have become of particular interest in that they display high tensile strength without vulcanization or filler reinforcement. In U.S. Patents Nos. 3,281,383 and 3,078,254» a process of making such radial block copolymers is described. Further, particular blends of butadiene-styrene block copolymers are described in U.S. Patent Nos. 3,646,101. In U.S. Patent No. 3,562,355, a mechanical blend of a butadiene-styrene copolymer in admixture with a polyester urethane is disclosed. The prior art nowhere describes radial block copolymers of the butadiene-styrene type containing particular ranges of butadiene and styrene which - 3 when admixed with specific other polymeric materials will form a plastics material composition having a sufficient elasticity and resealability so that the compositions are readily adaptable For use in formul5 ating plastic closure materials having reseal properties for contact with fluids to be administered to the body. Moreover, the prior art does not describe a plastic composition which is suitable for use in the medical plastics field and which will have sufficient low alkaline extraction values to ensure that ingredients in the composition are not extracted in with the fluids to be administered after contact with the closure material.

The present invention seeks to provide s novel admixture of radial block copolymers of the butadienestyrene type with certain other polymeric materials.

It further seeks to provide a thermoplastic, polymer composition of the radial block copolymer type which has a high degree of elasticity and resealability so that it can be employed as resealable injection sites in parenteral administration equipment, to provide a novel radial block copolymer mixture which can be readily molded, extruded and otherwise processed by customary processes, a thermoplastic polymer compos25 ition which is compatible and can be sealed or otherwise connected to other types of plastic materials in a parenteral administration set, a novel thermoplastic composition which is compatible with the usual plasticizers, fillers, chelators and lubricants, which are necessary in the fabrication of plastics materials.

According to the present invention there is provided a thermoplastic copolymer composition having 53534 - 4 elastic properties which consists essentially of (a) from 10$ to 90% by weight of a butadiene-styrene radial block copolymer having a butadiene content of from 60% to 85% by weight and a styrene content of from 15% to 40% by weight and an average molecular weight of 150,000 to 300,000 (b) from 90% to 10% by weight of a polymeric material which is an elastomeric polyolefin, an olefin copolymer or terpolymer, a vinyl acetate copolymer, a polyether or polyester urethane elastomer, an acrylic resin, a thermoplastic epoxide resin, polystyrene or a styrene copolymer other than an impact resistant styrene copolymer, a polycarbonate resin, an acetal resin, a polyamide, a vi.nylchloridc homopolymer or copolymer or a chlorin15 ated polyethylene, or a mixture of such materials.

In one preferred composition, the radial block copolymer may have a butadiene content of substantially 70$ by weight and a styrene content of 30% by weight and in another preferred composition the butadiene-styrene copolymer may have a butadiene content of substantially 60% by weight and in another preferred composition the butadiene-styrene copolymer may have a butadiene content of substantially 60% by weight and a styrene content of substantially 40% by weight. These copoly25 mers are preferably individually admixed with a polyether or polyester urethane elastomer or a mixture of chlorinated polyethylene and a polyether or polyester urethane elastomer in the proportion of 25 to 75% by weight of copolymer to 75 to 25$ by weight of elast30 outer or mixture of chlorinated polyethylene and elastomer.

In the following Examples, certain polymers, plasvicizers, chelators, lubricants and antioxidants 34 - 5 are referred to as components of the compositions of this invention. All of the materials are readily available on the commercial market and a brief summary of them follows: Produc t Polymers Trade Name Source Radial block copolymer (70:30 butadienestyrene) Solprene”411 Phillips Petroleum Co.

Radial block copolymer (6θ:4θ butadienestyrene ) Solprene11 414 Phillips Petroleum Co.

Chlorinated polyethylene CPE-3023 Dow Chemical Co.

Polyether urethane umer elastRoylar E-85 Uniroyal Chemical Co., Division of Uniroyal, Inc.

Plasticizer Mineral Oil U.S.P. grade Any available Lubeleant Montanic acid ester Wax OP American Hoechst Corp.

Antioxidants 0ctadeeyl-3-(3',5'-ditertbutyl-4Lhydroxyphenyl)propionate Irganox 1076 Ciba-Geigy 53534 - 6 Product Trade Name Source Antioxidants Tetrakis [methylene-313 *,5'-di-t-butylhydroxyphenyl)-propionate] methane Irganox 1010 Ciba-Geigy Corp.

Of the above the word Solprene11 is a Registered Trade Mark.

The invention is illustrated by the following 10 Examples.

Example 1.

Ingredients Formula by Parts $ Comp 15 Butadiene- styrene radial block copolymer (70:30) 100.0 70.30 Chlorinated polyethylene 41.0 28.82 Mineral oil 1.0 0.7 20 Antioxidant (octadecyl 3-( 3 ',5 '-ditert-butyl-4 hydroxyphenyl) propionate) 0.25 0.18 142 .45 100.00 Formulations were prepared from the above ingredients by mixing the formulation on a basis of 300 grams of butadiene-styrene radial block copolymer. The mater43S34 - 7 ials were fused on a standard two-roller mill at 300°325°F. and milled until a homogeneous blend was obtained. Pharmaceutical closures of the reseal type were made from ground portions of the roller milled sheet by transfer molding. Test results obtained on these materials are reported as follows: Properties Shore A hardness Reseal after piercing (lbs :.) 71 24 10 Coring None 100% Modulus (psi) 300 Ultimate tensile (psi) 2690 % Elongation 690 Compression set (%, 250°F. -2 hrs.) 102 IS Nephelos extraction 44 % Elongation 690 Example II. 20 ingredients Formula by Parts % Comp. Butadiene-styrene radial block copolymer (60:40) 100.0 70.3 Chlorinated polyethylene 41.0 28.82 Mineral oil 1.0 0.7 25 Antioxidant (octadecyl 3(3s ,5 -di.tert-butyl-4'hydroxyphenyl)propionate) 0.25 0.18 142 .25 100.00 - 3 10 The materials were prepared in the same manner as described in Example I and the properties found are listed as follows: Properties Shore A11 hardness Reseal after piercing (lbs.) Coring 100% Modulus (psi) Ultimate tensile (psi) % Elongation Compression set (%, 25O°F.-2 hrs.) Nephelos extraction % Elongation Example III.

Formula by Ingredients Parts Butadiene-styrene radial block-copolymer (70:30) 40.0 Chlorinated polyethylene 25.0 Polyether urethane elastomer 35.0 Lubricant (montanic acid ester) 0.25 Antioxidant (tetrakis [methylene-3(3',5'-di-tbutyl-4'-hydroxyphenyl )propionate]methane) 0.25 100.50 None 475 3350 650 121 650 % Comp. 39.80 24.88 34.82 0.25 0.25 100.00 The materials were prepared in the same manner as described in Example I and the properties found are listed as follows: 3 S 3 4 Properties Shore A hardness 69 Reseal after piercing (lbs. ) 31 Coring None 100% Modulus (psi) 360 Ultimate tensile (psi) 2970 Compression set (%, 250°F.-2 hrs.) 9? Nephelos extraction 23 % Elongation 590 Example IV. Ingredients Formula by Parts % Comp. Butadiene-styrene radial block copolymer (60:40) 40.0 39.8 Chlorinated polyethylene 25.0 24.88 Polyester urethane elastomer 35.0 34.82 Lubricant (montanic acid ester) 0.25 0.25 Antioxidant (tetrakis [methylene-3(31,5'-di-t- butyl-4 '-hydroxyphenyl )propionatejmethane) 0.25 0.25 100.50 100.00 The materials were prepared as described in Example 1 and the properties found are indicated as follows: Properties Shore A hardness Reseal after piercing (lbs.) 32 Coring None 100% Modulus (psi) 400 Ultimate tensile (psi) 2800 Compression set (%, 250°F.-2 hrs.) 94 Nephelos extraction 23 % Elongation 600 An explanation of the various tests used in the preceding Examples is as follows: (1) The 100% Modulus, Ultimate Tensile and % Elongation were obtained using ASTM Test Method: D-412-66 using a Type C die and an Instron Tensile Tester, (the word Instron is a Registered Trade Mark) (a) 100% Modulus is the force required to elongate the dumbbell-shaped sample 100% using a one-inch bench mark for reference. (b) Ultimate Tensile is the force per cross sectional area required to pull the sample apart. (c) % Elongation is the elongation of the sample at break. A one-inch bench mark is placed on the sampl before elongation. Then the distance between the marks at break minus one inch multiplied by 100 gives the per centage elongation. (2) Compression Set - the lower the figure, the better rubber replacement is obtained. The value of the compression set number indicates how much permanent deformation occurred after the sample was compressed. 3 5 3 j - 11 (3) Nephelos Extraction - this is an alkaline extraction, pH il. A low value indicates a clean product. (4) Reseal - this is an internally devised test which shows how much air pressure is necessary to break the seal of the diaphragm after piercing with a 20gauge needle five times. A high value indicates a very good reseal. (5) Shore A Hardness - also referred to as Shore A Durometer (ASTM-D-2240), is a procedure for determining the indentation hardness of materials. This method is based on a specified indentor forced into the material under specified conditions. (6) Coring - the determination of the resistance to cutting of a rubber-like material when repeatedly pierced by a new sharp hypodermic needle. This test usually measures the particulate fragments generated by such piercing.

In the foregoing Examples, specific thermoplastic materials were indicated as being incorporated as the additional polymeric materials. Other copolymers may be utilized to impart an elastomeric effect to the radial block copolymer composed of the butadiene styrene moieties so long as such copolymers will impart desired properties such as hot strength and resistance to cold flow, are compatible at working levels, are useful in nontoxie applications and can be processed at 300Η-4θθϋ1·. in the composition. These are elastomeric polyolefins, olefin copolymers and terpolymers, vinyl acetate copolymers, polyether and polyester urethane elastomers, acrylic resins, thermoplastic epoxides, polystyrene and styrene copolymers other than impact resistant polystyrenes, polycarbonates, acetal resins, polyamides and vinylchloride homopolymers and copolymers. - 12 Certain proportions of the radial block copolymers and polymeric materials are utilized in the Examples.

The proportions of radial block copolymer which can be effectively employed is from 25$ to 75$ by weight of the total weight of the composition and the polymeric material can be present in an amount of from 75$ to 25$ by weight of the total weight of the composition. These amounts are suitable when a radial block copolymer of butadiene and styrene is employed with chlorinated poly10 ethylene and a polyether or polyester urethane elastomer alone. When mixtures of the polymeric materials and the radial block copolymer are used, the preferred amounts may range from 75$ to 40$ by weight of such mixture to from 25$ to 60$ by weight of the radial block copoly15 mer.

Plasticizers may be incorporated into the foregoing compositions in varying proportions. These plasticizers are those authorised for use by the U.S. Food and Drug Administration. The preferred plasticizers are U.S.P. grade mineral oil and monomeric epoxidized esters in proportions of less than 30$ by weight. Chelators, lubricants, antioxidants, pigments and fillers may be incorporated into these compositions in required proportions.

As indicated by the Examples the compositions may be mixed or blended by conventional plastics materials or rubber mixing methods. For example, mixing may be done by simple tumbling, intensive mixers, open mill mixing, Banbury mixing or by extrusion and pelleting or dicing. The novel rubber-like compositions of this invention may be compression, transfer, injection or blow and extrusion molded according to standard plastics articles forming techniques. The resulting product - 13 may be of various shapes and configurations such as a pharmaceutical sealing component including a puncturable reseal device, a container closure, a syringe sealing ring or other rubber products such as syringe bulbs.

It will thus be seen that the present invention provides a novel rubber-like composition which by reason of its physical characteristics can be utilized as a pharmaceutical rubber composition in components for administering fluids to the body. The composition has a high degree of elasticity and resealability yet can be processed by various plastic and rubber fabricating techniques. Most importantly, the compositions have .a very low extraction value which makes them especially suitable for use in conjunction with parenteral. solutions.

Claims (9)

1. A thermoplastic copolymer composition having elastic properties which consists essentially of (a) from 10% to 90% by weight of a butadiene-styrene 5 radial block copolymer having a butadiene content of from 60% to 85% by weight and a styrene content of from 15% to 40% by weight and having an average molecular weight of 150,000 to 300,000 and (b) from 90% to 10% by weight of a polymeric material which 10 is an elastomeric polyolefin, an olefin copolymer or terpolymer, a vinyl acetate copolymer, a polyether or polyester urethane elastomer, an acrylic resin, a thermoplastic epoxide resin, polystyrene or a styrene copolymer other than an impact resistant 15 styrene copolymer, a polycarbonate resin, an acetal resin, a polyamide, a vinylchloride homopolymer or copolymer or a chlorinated polyethylene, or a mixture of such materials.

2. A thermoplastic composition as claimed in claim 1 20 wherein said radial block copolymer has a butadiene styrene content of substantially 70% by weight of butadiene and 30% by weight of styrene.

3. A thermoplastic copolymer composition as claimed in claim 1 wherein said radial block copolymer has a 25 butadiene-styrene content of substantially 60% by weight of butadiene and 4θ% by weight of styrene.

4. A thermoplastic copolymer composition as claimed in any of claims 1 to 3 wherein said polymeric material (b) is a polyether or polyester urethane 30 elastomer. - 15

5. A thermoplastic copolymer composition as claimed in any of claims 1 to 3 wherein said polymeric material (b) is a chlorinated polyethylene or polyether or polyester urethane elastomer present in a proportion of 75% to 25% by weight of said composition and said radial block copolymer is present in an amount of 25% to 75% by weight of said composition.

6. A thermoplastic copolymer composition as claimed in any of claims 1 to 3 wherein said polymeric material (b) consists of a mixture of chlorinated polyethylene and a polyether urethane elastomer and said radial block copolymer is present in a proportion of 25% to 60% by weight of the composition and said mixture of polymeric materials is present, i.n a portion of 75% to 40% by weight of the composition.

7. A thermoplastic copolymer composition as claimed in any of claims 1 to 6 which has been molded to form a pharmaceutical sealing component. S. A thermoplastic copolymer composition according to claim 7 in the form of a puncturable reseal device, a container closure, a syringe plunger sealing ring or a rubber-like syringe, bulb.

8.

9. A thermoplastic copolymer composition as claimed in claim 1 and substantially as hereinbefore described with reference to any one of the Examples.