Abstract:
Radial block copolymers are blended with additional polymeric materials to form rubber-like plastic compositions having high elastic and reseal properties so that they can be utilized as a rubber replacement in the fabrication of resealable injecton sites in intravenous administration equipment and stoppers for containers where resealability after puncture is also a desirable property.

Description:
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 substitued olefin butadiene-styrene type which have blended with them certain polymeric materials to form a plastic composition having a high degree of elasticity and resealability so as to be useful as puncturable reseal units in parenteral administration equipment as well as in containers for materials intended for administration to the body. 
     Recently, radial block polymers of the butadiene-styrene type have been of particular interest in that they display high tensile strength without vulcanization or filler reinforcement. In U.S. Pat. Nos. 3,281,283 and 3,078,254, a process of making such radial block copolymers is 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 quantity and when combined with certain polymeric materials will form a plastic composition having a sufficient elasticity and resealability so that they are readily adaptable for use in composing plastic closure materials having reseal properties for contact with fluids to be administered to the body. In addition, the prior art nowhere describes a plastic composition which is readily suitable for use in the medical plastics field which will have sufficiently low alkaline extraction nephelos values so that ingredients in the composition are not extracted in with the fluids to be administered after contact with the closure material. 
     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 elasticity and resealability so that they can be employed as a pharmaceutical sealing component such as resealable injection sites in parenteral administration equipment without coring, a novel radial block copolymer mixture which can be readily molded, extruded and otherwise processed by customary processes, a thermoplastic material which is compatible and can be sealed or otherwise connected to other types of plastic materials in a parenteral administration set, a novel plastic composition 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 (a) 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, (b) from about 90 - 10% by weight of a butadiene-styrene radial block copolymer having differing butadiene and styrene contents, but falling within the range of about 85 - 60% by weight and a styrene content in the range of about 15 - 40% by weight which can be incorporated with (c) 3 - 75% by weight of certain polymeric materials including polyolefin-butyl rubber graft copolymers, chlorinated polyethylene, styrene-olefin block copolymers, polyether urethane elastomers, polyisobutylene and mixtures thereof which will provide a nonclear material which can be punctured without coring. 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 of about 3:1 parts by weight to the copolymer having the 60:40 butadiene-styrene content. 
     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             Petroleumbutadiene-styrene)         Co.Radial block co-         Solprene 414 Phillipspolymer (60:40             Petroleumbutadiene-styrene)         Co.Polyolefin-butyl         ET-L-3100    Alliedrubber grafted             Chemicalcopolymer                  Corp.Styrene-olefin         Telcar 101   B. F. Good-block copolymer            rich Chemi-                      cal Co.,                      Division of                      B. F. Good-                      richChlorinated poly-         CPE-3623     Dow Chemi-ethylene                   cal Co.Polyether urethane         Roylar E-85  Uniroyalelastomer                  Chemical Co.,                      Division of                      Uniroyal,                      Inc.Polyisobutylene         Vistanex 120 Exxon Chemi-                      cal Co, U.S.A.PlasticizerMineral oil      --        Any availa-U.S.P. grade               bleLubricantsMono fatty acid         Loxial G-40  Henkel, Inc.ester of fattyalcoholsComplex ester of         Loxiol G-73  Henkel, Inc.unsaturated fattyacidMontanic acid Wax OP       Americanester                      Hoechst Corp.Oxidized poly-         AC629A       Allied Chem-ethylene wax               ical Co.AntioxidantsHindered phenol         Mark 1220    Argus Chem-                      ical Corp.,                      Subsidiary                      of Witco                      Chemical Co.Butylated hydroxy         Ionol CP     Shell Chem-toluene                    ical Co.Octadecyl 3-(3&#39;,5&#39;-         Irganox 1076 Ciba-Geigyditert-butyl-4&#39;-           Corp.hydroxyphenyl)propionateTetrakis [methyl-         Irganox 1010 Ciba-Geigyene-3(3&#39;,5&#39;-di-t-          Corp.butyl hydroxyphenyl)propionate]methaneHindered phenol         Mark 1883    Argus Chem-                      ical Corp.,                      Subsidiary                      of Witco                      Chemical Co.______________________________________ 
    
    
    
     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              byIngredients        Parts       % Comp.______________________________________Radial block copolymer              37.5       33.94(70:30 butadiene-styrene)Radial block copolymer              12.5       11.30(60:40 butadiene-styrene)Polyolefin-butyl rubber              50.0       42.25grafted copolymerChlorinated polyethylene              10.0       9.20Lubricant (mono fatty acid              0.25       0.23ester of fatty alcohols)Antioxidant (hindered phenol)              0.25       0.23Mark 1220          110.50     100.00______________________________________ 
    
     Formulations were prepared with the above ingredients by mixing the formulation on a base of 300 grams of butadiene-styrene radial block copolymers. The materials were fused on a standard two-roll mill at 300° - 325° F. and milled until a homogeneous blend was obtained. Pharmaceutical closures of the intravenous bag reseal type were made from ground portions of the roll milled sheet by transfer molding. Test results made on these materials are indicated in in Table I. 
     EXAMPLE II 
     
         ______________________________________              Formula              byIngredients        Parts      % Comp.______________________________________Radial block copolymer              75.0       59.80(70:30 butadiene-styrene)Radial block copolymer              25.0       19.90(60:40 butadiene-styrene)Styrene-olefin block              15.0       12.00copolymerMineral oil        10.0       8.00Lubricant (complex ester              0.25       0.15of unsaturated fatty acid)Antioxidant (butylated              0.25       0.15hydroxy toluene)   125.50     100.00______________________________________ 
    
     The materials were prepared in the same manner as in Example I and the properties of the materials are shown in Table I. Pharmaceutical closures of the intravenous bag reseal type were made from this material. 
     EXAMPLE III 
     
         ______________________________________              Formula              byIngredients        Parts      % Comp.______________________________________Radial block copolymer              75.0       52.72(70:30 butuadiene-styrene)Radial block copolymer              25.0       17.56(60:40 butadiene-styrene)Chlorinated polyethylene              41.0       28.82Mineral oil        1.0        0.70Antioxidant (octadecyl 3-              0.25       0.20(3&#39;,5&#39;-ditert-butyl-4&#39;-hyroxyphenyl)propionate)              142.25     100.00______________________________________ 
    
     The materials were prepared in the same manner as described in Example I and the properties are shown in Table I. Pharmaceutical parts such as a 28 mm. I.V. container closure and a unit dose syringe plunger were made from this compound. 
     EXAMPLE IV 
     
         ______________________________________              Formula              byIngredients        Parts      % Comp.______________________________________Radial block copolymer              30.0       29.85(70:30 butadiene-styrene)Radial block copolymer              10.0       9.95(60:40 butadiene-styrene)Chlorinated polyethylene              25.0       24.88Polyether urethane elastomer              35.0       34.82Lubricant (montanic acid              0.25       0.25ester)Antioxiant (tetrakis [methyl-              0.25       0.25ene-3(3&#39;,5&#39;-di-t-butyl hydroxy-phenyl)propionate]methane)              100.5      100.00______________________________________ 
    
     The materials were prepared as described in Example I and the results of the physical properties are shown in Table I. Pharmaceutical parts, such as a unit dose syringe plunger and a 28 mm. closure, were made from this formulation. It should be noted that the addition of the polyether urethane in this Example as compared to Example III gives improved reseal and lower extraction. 
     EXAMPLE V 
     
         ______________________________________              Formula              byIngredients        Parts      % Comp.______________________________________Radial block copolymer              75.0       63.80(70:30 butadiene-styrene)Radial block copolymer              25.0       21.30(60:40 butadiene-styrene)Polyisobutylene    16.0       13.60Mineral oil        1.0        0.90Lubricant (oxidized poly-              0.25       0.20ethylene wax)Antioxidant (hindered phenol)              0.25       0.20Mark 1883          117.50     100.00______________________________________ 
    
     The materials were prepared as described in Example Table I and the results of the physical properties are shown in Table I. The formulation presented in this Example has the best reseal characteristics of all and it borders on being clear. Unpigmented, it is very transluscent. Pharmaceutical parts such as an intravenous set reseal, I.V. bag reseal and 28 mm. closure were molded from this formulation. 
     
                                           Table I__________________________________________________________________________COMPARISON OF 75:25 BLEND OF RADIAL BLOCK COPOLYMERS TO THE SEPARATERADIAL BLOCK COPOLYMERS__________________________________________________________________________               (1a) (1b)                            (5)               100% Ultimate                           (1c)   (2)    (3)    (4) Reseal     Radial Block               Modulus                    Tensile                           %      Compression                                         Nephelos                                                Shore                                                    PressureFormulation     Copolymer (psi)                    (psi)  Elongation                                  Set %  Extract.                                                &#34;A&#34; (lbs.)__________________________________________________________________________     75-Solprene 411Example I               350  1000   480    72     precipitate                                                60  17     25-Solprene 414     Solprene 411               225  440    430    104    precipitate                                                59  20     Solprene 414               275  420    300    120    precipitate                                                60  10     75-Solprene 411Example II               370  2000   550    88.2   38     66  32     25-Solprene 414     Solprene 411               340  780    520    94.1   40     69  9     Solprene 414               440  1400   490    104    41     77  5     75-Solprene 411Example III               300  3350   700    27.4   38     69  40     25-Solprene 414     Solprene 411               300  2690   690    102    44     71  24     Solprene 414               475  3350   650    121    54     76  20     75-Solprene 411Example IV               400  3010   600    85     17     71  35     25-Solprene 414     Solprene 411               360  2970   590    98     18     69  31     Solprene 414               460  2850   590    94     23     77  32     75-Solprene 411Example V               285  2425   680    44.9   16     70  40     25-Solprene 414     Solprene 411               250  1610   630    92     22     69  30     Solprene 414               450  2860   640    114    38     80  36__________________________________________________________________________ 
    
     An explanation of the various tests 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. 
     a. 100% Modulus is the force required to elongate the dumbbell-shaped sample 100% using a 1-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. 
     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. Nephelos Extraction -- this is an alkaline extraction, pH 11. A low value indicates a clean compound. 
     4. Shore &#34;A&#34; Durometer (ASTM-D-2240) is a procedure for determining indentation hardness of materials. This method is based on a specified indentor forced into the material under specified conditions. 
     5. Reseal -- this is an internal devised test which shows how much air pressure is necessary to break the seal of the diaphragm after piercing with a 20 gauge needle five times. A high value indicates very good reseal. 
     It will be noted in Table I that comparative data is given for the Solprene 411 and Solprene 414 in comparison with the five Examples. These formulations were individually composed using the Solprene 411 and the Solprene 414 alone with all other ingredients of the composition being the same as they were for the combination of the 75:25 Solprene 411 and 414 radial block copolymers. The Table indicates that improved properties are obtained when utilizing the combination of the two radial block copolymers with the added polymeric material to obtain the desired elastomeric properties. 
     In the foregoing Examples, certain thermoplastic materials were indicated as being incorporated with the additional polymers or copolymers. It should be understood that other copolymers which could be utilized to have an elastomeric effect on the combined radial block copolymers composed of the butadiene-styrene moieties could be incorporated as long as they 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; be noncoring and nonclear. These would include polymers or copolymers of the following types: styrene acrylonitrile, acetyls, polyamides, polybutenes, polyesters, polyolefins, polymethyl pentenes, polystyrene, and mixtures thereof. However, the preferred additive polymeric materials are polyolefin-butyl rubber graft copolymers, chlorinated polyethylene, styrene-olefin block copolymers, polyether urethane elastomers, and mixtures of these. 
     Certain amounts of the polymeric materials are indicated in the Examples. If desired, other quantities of these in relation to the radial block copolymers could be employed as follows: chlorinated polyethylene 3 to 35%; styrene-olefin block copolymers 3% to 12%; polyether urethane elastomers 3 to 50%; polyisobutylene 3% to 25%; mixtures of polyolefin-butyl rubber grafted copolymer and chlorinated polyethylene 3 to 33%; polyether urethane elastomer and chlorinated polyethylene 3 to 60%; 3 - 50% of polyester urethane elastomer and chlorinated polyethylene and 3 - 50% of polyolefin-butyl rubber grafted copolymer and external plasticizer. 
     Plasticizers may be incorporated into the foregoing compositions in varying concentrations. 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 30% by weight. Of course, chelators, lubricants, antioxidants, pigments and fillers may be incorporated into these 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 novel plastic compositions of this invention can be compression, transfer or injection molded according to standard plastic fabrication techniques. The resulting product can be of various shapes and configurations such as a pharmaceutical sealing component including a puncturable reseal device, a container closure or a syringe sealing ring. When the composition is in the form of a reseal device, it can be punctured without coring which is determined by the cut resistance to a new, sharp hypodermic needle and the particulate fragments generated, if any. Further, the compositions of this invention can be molded into rubber-like syringe bulbs. 
     Table II shows the properties obtained with twenty radial block copolymer combinations of differing butadiene-styrene contents. Conclusions which can be drawn from this data are: 
     1. Shore &#34;A&#34; durometer increases with higher styrene content. Higher durometers are suitable for plastics molded parts while lower durometers are favored for closures. 
     2. Tensile strength increases with styrene content and preferred ranges lie above 25% styrene. 
     3. Ultimate elongation shows desired maxima between 25 and 37% styrene. 
     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%, 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 20 radial block copolymer formulations the additional polymers and additives employed in conjunction with the radial block copolymers are the same as 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 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 very low extraction values which makes them especially suitable for use in conjunction with 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 II__________________________________________________________________________   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       100Copolymer D 25   150          100              22.6 52   67 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% Styrene 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 33Copolymer D 25   150                      50   33   16 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 Wt. 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__________________________________________________________________________