Abstract:
Radial block copolymers are mechanically combined with additional polymeric materials to form plastic compositions having a high degree of clarity so that they can be substituted for polyvinylchloride plastic compositions in the fabrication of such devices as intravenous and blood tubing, containers for intravenous solutions and blood fractions, functional parts of intravenous administration equipment such as sight and drip chambers, needle adapters and miscellaneous assemblies for contact with intravenous fluids. The compounds of this invention can also be utilized for catherization, bodily drainage systems, and as pharmaceutical closures, resealable injection sites and syringe plunger tips.

Description:
CROSS REFERENCE TO RELATED APPLICATIONS 
     This is a division of application Serial No. 607,978, filed Aug. 26, 1975 and issued as U.S. Pat. No. 4,048,254. 
    
    
     BACKGROUND OF THE INVENTION 
     This invention relates to thermoplastic polymers which are useful in molding plastic materials for contact with body fluids. More particularly, it relates to a thermoplastic polymer composed of block radial polymers of the diene-aryl substituted olefin butadiene-styrene type which have blended with them certain polymeric materials to form a plastic composition having a high degree of clarity which are particularly useful in extruding or molding tubing, drip chambers and other components useful in the field of parenteral administration. 
     Recently, radial block polymers of the diene-aryl substituted olefin butadiene-styrene type have been of particular interest in that they display high tensile strength without vulcanization or filler reinforcement. These copolymers can be processed on conventional plastics or rubber equipment without the addition of plasticizers. In U.S. Pat. Nos. 3,281,383 and 3,079,254, processes for making such radial block copolymers are described. Further, particular blends of vulcanized butadiene-styrene block copolymers are indicated in U.S. Pat. No. 3,646,161. In U.S. Pat. No. 3,562,355, a mechanical blend of a butadiene-styrene copolymer is described in combination with a polyester urethane. The prior art nowhere describes a blend of nonvulcanized radial block copolymers of the butadiene-styrene type wherein the butadiene-styrene amounts are of a certain minimum quantity so that when they are combined with certain polymeric materials, they will form a plastic composition having a sufficient clarity, hardness, tensile strength and elongation to be readily adaptable for use in composing plastic materials for contact with parenteral fluids. In addition, the prior art nowhere describes a plastic composition which is readily suitable for use in the medical plastics field which will have low alkaline extraction values so that ingredients in the composition are not extracted into the fluids to be administered. 
     It is an advantage of the present invention to provide a novel blend of radial block copolymers of the butadiene-styrene type with other polymeric materials. Other advantages are a thermoplastic composition of the radial block copolymer type which have a high degree of clarity so that they can replace polyvinylchloride as a material in the forming of medical plastic product such as tubing, drip chambers, injection reseal device and other parenteral administration equipment, a novel radial block copolymer mixture which can be readily molded, extruded and otherwise processed by customary processes, a thermoplastic material which is compatible with the usual plasticizers, fillers, chelators, lubricants, etc. which are necessary in the fabrication of plastic materials. 
     SUMMARY OF THE INVENTION 
     The foregoing advantages are accomplished and the shortcomings of the prior art are overcome by the present radial block copolymer mixture which is composed of from about 10-90% by weight of a butadiene-styrene radial block copolymer having a butadiene content in the range of about 85-60% by weight and a styrene content in the range of about 15-40% by weight, from about 90-10% by weight of a butadiene-styrene radial block copolymer having differing butadiene contents in the range of about 85-60% by weight and a styrene content in the range of about 15-40% by weight and 5-75% by weight of the radial block copolymer of certain polymeric or copolymeric materials such as acrylics, thermoplastic epoxides, styrene acrylonitrile, polycarbonates, polybutenes and polyisobutylenes, polyesters, polyolefins, polystyrenes, polyvinylchloride and olefin/P.V.C. copolymers, polyether and polyester urethane polymers and methacrylate-styrene-butadiene copolymers and mixtures thereof. Of the foregoing those preferred are thermoplastic polyether urethane polymers, methyl methacrylate-styrene-butadiene copolymers, methyl methacrylate-acrylonitrile-styrene-butadiene copolymers and thermoplastic polyester urethane polymers, and mixtures thereof. In a preferred composition, one of the radial block copolymers has a butadiene content of about 70% by weight and a styrene content of 30% by weight and the other butadiene-styrene copolymer has a butadiene content of about 60% by weight and a styrene content of about  40% by weight with the copolymer having the 70:30 butadiene-styrene ratio present in an amount in the range of about 90-45% by weight with the polymer having the 60:40 butadiene-styrene ratio present in the range of about 10-55% by weight with a 75 to 25% ratio preferable. 
     DESCRIPTION OF THE PREFERRED EMBODIMENT 
     In the following Examples, certain polymers, plasticizers, chelators, lubricants, antioxidants, etc. are referred to in composing the novel compositions of this invention. All of the materials are readily available on the commercial market and a brief explanation of them is given: 
     
         ______________________________________Product       Trade Name   Source______________________________________PolymersRadial block co-         Solprene 411 Phillipspolymer (70:30             Petroleum Co.butadiene-styrene)Radial block co-         Solprene 414 Phillipspolymer (60:40             Petroleum Co.butadiene-styrene)Butadiene-styrene-         Acryloid     Rohm &amp; Haasmethyl methacrylate         KM-636       Co.polymerThermoplastic poly-         Roylar E-85  Uniroyalether urethane             Chemical Co.,                      Division of                      Uniroyal, Inc.Butadiene-styrene-         Acryloid     Rohm &amp; Haasmethyl methacrylate         KM-641       Co.polymerButadiene-styrene-         Blendex      Marbon Divi-methacrylate- 435          sion, Borg-acrylonitrile              Warner Corp.polymerThermoplastic poly-         Roylar       Uniroyalether urethane         E-80         Chemical Co.,polymer                    Division of                      Uniroyal, Inc.Thermoplastic poly-         Estane 5701  B. F. Goodrichester urethane             Chemical Co.,polymer                    Division of                      B. F. GoodrichProcessing AidAcrylic processing         Acryloid     Rohm &amp; Haasaid           K-175        Co.PlasticizersMonomeric epoxy         Epoxol 8-2B  Swift Chemi-                      cal Co., Di-                      vision of                      Swift and                      CompanyMineral oil   --           Any avail-U.S.P. grade               ableChelatorTris nonyl phenyl         Mark 1178    Argus Chemi-phosphite                  cal Co.,                      Division of                      Witco Chem-                      ical Co. LubricantsMono fatty acid         Loxiol G-40  Henkel, Inc.ester of fattyalcoholsDiglyceryl ester         Loxiol G-16  Henkel, Inc.of unsaturatedfatty acidsComplex ester of         Loxiol G-71  Henkel, Inc.unsaturated fatty         &amp; G-73acidsAntioxidantsOctadecyl 3-(3&#39;,5&#39;         Irganox      Ciba-Geigyditert-butyl-4&#39;-         1076hydroxyphenyl)propionate2,4 ditert.-p-         Ionol CP     Shell Chemi-butyl cresol               cal Co.Tetrakis-[methyl-         Irganox      Ciba-Geigyene-3-(3&#39;,5&#39; di-t-         1010butyl-4&#39;-hydroxy-phenyl)propionate]methane______________________________________ 
    
    
    
     The invention is disclosed in further detail by means of the following Examples which are set forth for the purpose of illustrating the invention, but, in no way are to be construed as limiting the invention to the precise amounts, ingredients or conditions indicated. 
     EXAMPLE I 
     
         ______________________________________              Formula              by Ingredients       Parts      % Comp.______________________________________Radial block copolymer              75.0       58.73(70:30 butadiene-styrene)Radial block copolymer              25.0       19.58(60:40 butadiene-styrene)Butadiene-styrene-methyl              10.0       7.83methacrylate polymer(Acryloid KM-636)Thermoplastic polyether              10.0       7.83urethane polymer(Roylar E-85)Monomeric epoxy plasticizer              5.0        3.91Chelator (tris nonyl phenyl              0.5        0.39phosphite)Lubricant (mono fatty acid              2.0        1.57ester of fatty alcohols)Antioxidant (octadecyl 3-              0.2        0.16(3&#39;-5&#39; ditert.-butyl-4-hydroxyphenyl)propionate)              127.7      100.00______________________________________ 
    
     The proper amount of ingredients are weighed out and placed in a low shear blender such as a Prodex-Henschel or a ribbon blender. The ingredients are mixed at a low speed for approximately five minutes to assure a good, dry blend. The resulting finished compound can then either be stored in proper containers for future use in extrusion, injection molding, transfer molding, etc. For tubing extrusion in a 2 or 21/2 inch 24/1 L/D extruder, the compound is placed in a hopper and extruded using a single stage screw with heat zones between 300°-400° F. Tubing was extruded at a rate of 100 feet per minute and had an internal diameter of 0.100 inch and an outside diameter of 0.138 inch. The tubing was extruded in 3,000 foot lengths. For best transfer molding results, the compounds should be fused first into a slab form. The compound can also be injection molded as a dry blend or in pelletized form. Typical properties for the resulting material when fabricated as a female needle adapter with luer fittings at one end and tubing connector sleeve at the other end or as an I.V. bag reseal were as follows: 
     
         ______________________________________  Shore &#34;A&#34;  100%      Ultimate                               Ultimate %Clarity  Durometer  Modulus   Tensile Elongation______________________________________+5     74         300       1875    697______________________________________ 
    
     EXAMPLE II 
     
         ______________________________________              Formula              by Ingredients       Parts      % Comp.______________________________________Radial block copolymer              75.0       67.10(70:30 butadiene-styrene)Radial block copolymer              25.0       22.40(60:40 butadiene-styrene)Butadiene-styrene-methyl              10.0       9.00methacrylate polymer(Acryloid KM-641)Chelator (tris nonyl phenyl              0.5        0.40phosphite)Lubricant (diglyceryl ester              1.0        0.90of unsaturated fatty acids)Antioxidant (tetrakis-[methyl-              0.2        0.17ene-3-(3&#39;,5&#39; di-t-butyl-4&#39;-hydroxyphenyl)propionate]methane)              111.7      100.00______________________________________ 
    
     The mixing and molding procedures were the same as in Example I and a product when fabricated into tubing having the same internal and outside diameters had the following: 
     
         ______________________________________  Shore &#34;A&#34;  100%      Ultimate                               Ultimate %Clarity  Durometer  Modulus   Tensile Elongation______________________________________+3     75         358       3292    673______________________________________ 
    
     EXAMPLE III 
     
         ______________________________________               Formula               by Ingredients        Parts      % Comp.______________________________________Radial block copolymer               75.0       65.96(70:30 butadiene-styrene)Radial block copolymer               25.0       22.00(60:40 butadiene-styrene)Butadiene-styrene-methacrylate-               10.0       8.79acrylonitrile polymerMonomeric epoxy plasticizer               2.0        1.76Chelator (tris nonyl phenyl               0.5        0.44phosphite)Lubricant (mono fatty acid               1.0        0.88ester of fatty alcohols)Antioxidant (2,4 ditert.-p-               0.2        0.17butyl cresol)               113.7      100.00______________________________________ 
    
     The mixing and molding procedures were the same as in Example I. The typical properties for a product when fabricated into the same size of tubing were as follows: 
     
         ______________________________________  Shore &#34;A&#34;  100%      Ultimate                               Ultimate %Clarity  Durometer  Modulus   Tensile Elongation______________________________________+3     77         400       3017    657______________________________________ 
    
     EXAMPLE IV 
     
         ______________________________________               Formula               by Ingredients        Parts      % Comp.______________________________________Radial block copolymer               75.0       65.96(70:30 butadiene-styrene)Radial block copolymer               25.0       22.00(60:40 butadiene-styrene)Thermoplastic polyether               10.0       8.79urethane polymer (Roylar E-80)Monomeric epoxy plasticizer               2.0        1.76Chelator (tris nonyl phenyl               0.5        0.44phosphite)Lubricant (complex ester of               1.0        0.88unsaturated fatty acids,Loxiol G-71)Antioxidant (2,4 ditert.-p-               0.2        0.17butyl cresol)               113.7      100.00______________________________________ 
    
     The mixing and molding procedures were the same as in Example I and the typical properties for a product when fabricated into the same size tubing and 13 and 20 mm. bottle closures were as follows: 
     
         ______________________________________  Shore &#34;A&#34;  100%      Ultimate                               Ultimate %Clarity  Durometer  Modulus   Tensile Elongation______________________________________+4     75         350       3233    700______________________________________ 
    
     EXAMPLE V 
     
         ______________________________________               Formula               by Ingredients        Parts      % Comp.______________________________________Radial block copolymer               75.0       66.55(70:30 butadiene-styrene)Radial block copolymer               25.0       22.18(60:40 butadiene-styrene)Thermoplastic polyester               9.0        7.99urethane polymerMonomeric epoxy plasticizer               2.0        1.77Chelator (tris nonyl phenyl               0.5        0.44phosphite)Lubricant (diglyceryl ester of               1.0        0.89unsaturated fatty acids)Antioxidant (2,4 ditert.-p-               0.2        0.18butyl cresol)               112.7      100.00______________________________________ 
    
     The mixing and molding procedures were the same as in Example I and the typical properties for a product when fabricated into the same size of tubing and flexible &#34;Y&#34; reseal for I.V. sets were as follows: 
     
         ______________________________________  Shore &#34;A&#34;  100%      Ultimate Ultimate %Clarity  Durometer  Modulus   Tensile  Elongation______________________________________+4     78         367       3175     697______________________________________ 
    
     EXAMPLE VI 
     
         ______________________________________               Formula               by Ingredients        Parts      % Comp.______________________________________Radial block copolymer               37.5       23.78(70:30 butadiene-styrene)Radial block copolymer               12.5       7.93(60:40 butadiene-styrene)Butadiene-styrene-methyl               100.0      63.40methacrylate polymer(Acryloid KM-641)Acrylic processing aid               3.0        1.90Lubricant (complex esters of               2.0        1.27unsaturated fatty acids,Loxiol G-73)Chelator (tris nonyl phenyl               0.5        0.32phosphite)Antioxidant (2,4 ditert.-p-               0.2        0.13butyl cresol)Plasticizer (mineral oil,               2.0        1.27U.S.P. grade)               157.7      100.00______________________________________ 
    
     The mixing and molding procedures were the same as in Example I and the typical properties for these ingredients when molded into a semirigid luer type needle adapter and sight chamber were as follows: 
     
         ______________________________________  Shore &#34;A&#34;  100%      Ultimate Ultimate %Clarity  Durometer  Modulus   Tensile  Elongation______________________________________+2     80         800       2300     450______________________________________ 
    
     Concerning the composition in Example VI, it should be pointed out that the clarity of this compound can be improved by using a different butadiene-styrene-methyl methacrylate polymer or butadiene-styrene-methyl methacrylateacrylonitrile polymer and eliminating the acrylic processing aid or making a lubricant substitution. 
     In the preceding Examples and following Table I, certain tests are referred to for the thermoplastic products formed by this invention. They are described as follows: 
     &#34;Clarity&#34; -- A grading using plasticized polyvinylchloride as a comparative control of +5. 
     The 100% Modulus, Ultimate Tensile and Ultimate % Elongation were obtained using ASTM Test Method: D-412-66 using a Type C die and an Instron Tensile Tester. 
     (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 sample before elongation. Then the distance between the marks at break minus one inch times 100 gives the percent elongation. 
     Shore &#34;A&#34; Durometer is a procedure for determining indentation hardness of materials (ASTM-D-2240). The method is based on a specified indentor forced into the material under specified conditions. 
     In the foregoing Examples I and IV, a thermoplastic polyether urethane polymer was referred to. These polymers are the linear reaction products of polyether glycols and aromatic diisocyanates. In addition to being clear, they are especially suitable for forming reseal devices such as injection sites and pierceable stoppers because of their elastomeric properties. The urethane polymers of the thermoplastic polyester type utilized in Example V are the reaction products of linear hydroxyl terminated aliphatic polyesters, an aromatic diisocyanate and an aliphatic diol. Further, methyl methacrylate-styrene-butadiene copolymers are indicated for use with the blend of the radial block styrene-butadiene copolymers as well as methyl methacrylate-acrylonitrile-styrene-butadiene copolymers. Other polymers or copolymers which could be utilized and still provide a degree of clarity with the basic blend of radial block copolymers would be those which will impart unique properties such as hot strength and resistance to cold flow; will be compatible at working levels; can be used in nontoxic applications; will process at 300°-400° F. in the compound. These would include the following polymers or copolymers: acrylics, thermoplastic epoxies, polycarbonates, and polyisobutylenes, polyesters, polyvinylchloride and olefin/P.V.C. copolymers. 
     Certain components are utilized as being fabricated from the radial block copolymer mixture of this invention. Others would include various types of closures such as pharmaceutical closures, flexible containers, syringe plunger tips and elastomeric bulbs. 
     Certain amounts of the polymeric materials in relation to the combined weight of the radial block copolymers are indicated in the Examples. These amounts can be adjusted and still provide the advantages of this invention. For example, the amount of the methyl methyacrylate-styrene-butadiene copolymers can be present in an amount in the range of about 5 parts by weight to about 200 parts by weight per 100 parts by weight of the combined radial block copolymers; the polyether urethane in an amount in the range of about 10 to about 50 parts by weight per 100 parts by weight of the combined radial block copolymers; the polyester urethane in an amount not exceeding 50 parts by weight; and the methyl methacrylate-acrylonitrile-butadiene-styrene in an amount in the range of about 10 to about 70 parts per 100 parts by weight of the radial copolymers. 
     Plasticizers may be incorporated into the foregoing compositions in varying concentrations in amounts of about 2 to about 50 parts by weight per 100 parts by weight of the combined radial block copolymers. These plasticizers would be those sanctioned for use by the U.S. Food and Drug Administration. The preferred choices are U.S.P. grade mineral oil and monomeric epoxidized esters in low concentrations, i.e. less than 10% by weight. Of course chelators, lubricants, antioxidants, pigments and fillers may be incorporated into those compositions in required concentrations. As indicated in the Examples, the compositions may be mixed or blended by conventional plastics or rubber methods. For example, mixing may be done by simple tumbling, intensive mixers, open mill mixing, Banbury mixing or by extrusion and pelletizing or dicing. The resulting product can be of various shapes and configurations such as plastic tubing or a drip chamber. 
     The Table shows the properties obtained with 20 radial block copolymer combinations of differing butadiene-styrene contents. Conclusions and applications which can be made from this data are: 
     1. The Shore &#34;A&#34; durometer increases with the higher styrene content. Higher durometers are suitable for plastics molded parts, whereas lower durometers are favored for closures. 
     2. Tensile strength increases with styrene content and preferred ranges lie above 25% styrene content. 
     3. Ultimate elongation shows a desired maxima between 25 and 37% styrene content. 
     4. One-hundred percent modulus increases with styrene content. Higher values above 30% styrene content are desired for plastics usage in tubing and plastics molded parts. Lower values, below 30% styrene, would be desirable in closure applications. 
     5. Alkaline extraction decreases with increased styrene content. It is desired to obtain the lowest values. 
     6. Optimum clarity is found between 25-35% styrene content. 
     It should be pointed out that in all of twenty radial block copolymer formulations the additional polymers and additives employed in conjunction with the radial block copolymers are the same and are illustrated in the previous Examples. It will also be seen from the Table that the preferred average molecular weight of the blend of the radial block copolymers is between 150,000 and 270,000. 
     It will thus be seen that through the present invention there is provided a novel plastic composition which through its physical characteristics can be utilized to compose various components for administering fluids to the body. The composition has a high degree of clarity yet can be processed by various plastic and rubber fabricating techniques. Most importantly, the compositions have very low extraction values which makes them especially suitable for use in handling parenteral solutions. 
     The foregoing invention can now be practiced by those skilled in the art. Such skilled persons will know that the invention is not necessarily restricted to the particular embodiments presented herein. The scope of the invention is to be defined by the terms of the following claims as given meaning by the preceding description. 
     
                                           TABLE I__________________________________________________________________________   Styrene        Molec.   %    Wt. × 1,000               1   2   3   4   5   6   7   8    9    10 A 30   300                        75  77.4                                           48   33   77.4Radial B 40   150    100                 25Block C 30   150        100Copoly- D 25   150            100             22.6                                           52   67mer   E 15   150                100                       22.6 F 40   250                    100Additional Polymers and Additives               27.7                   27.7                       27.7                           27.7                               27.7                                   27.7                                       27.7                                           27.7 27.7 27.7Avg. Molecular Wt. of Blend × 1,000               150 150 150 150 250 262.5                                       266.1                                           222  200.5                                                     266.1% Sytrene in Blend  40  30  25   15  40 32.5                                       29  27.8 27   26.6100% Modulus - psi  442 250 225 100 467 300 293 263  250  272Ultimate Tensile Strength-psi               778 673 693 140 3450                                   2430                                       2583                                           1338 1100 1605Ultimate Elongation-%               467 527 610 457 677 713 740 667  647  720Alkaline Extraction Nephelos Units               22  47  49   42  13  3  26  30   42   33Shore &#34;A&#34; Durometer 65  55  45   27  80 70  64  55   56   58Relative Clarity    +3  +4  +3  +2  +2  +5  +4  +5   +5   +4   Styrene        Molec.   %    Wt. × 1,000               11  12  13  14  15  16  17  18   19   20 A 30   300    48  33Radial B 40   150            25Block C 30   150            75  50  33Copoly- D 25   150                        50  33mer E 15   150    52  67                           33   16 F 40   250                50  67  50  67  84   67   84Additional Polymers and Additives               27.7                   27.7                       27.7                           27.7                               27.7                                   27.7                                       27.7                                           27.7                                             27.7     27.7Avg. Molecular of Blend × 1,000               222 200.5                       150 200 217 200 217 234                                             217     234% Styrene in Blend  23.3                   20  32.5                            35 36.7                                   32.5                                       35  38                                             31.6    35.9100% Modulus-psi    217 175 283 333 425 237 352 417                                             293     373Ultimate Tensile Strength-psi               815 532 707 1842                               3328                                   980 2847                                           3358                                             1633    3007Ultimate Elongation-%               637 617 517 650 707 630 713 710                                             687     713Alkaline Extraction Nephelos Units               59  50  40   26  18 37  29  19                                             39      24Shore &#34;A&#34; Durometer 49  41  58   69  77 50  70  77                                             61      74Relative Clarity    +3  +4  +5  +4  +3  +5  +4  +3                                             +5      +3__________________________________________________________________________