MXPA99010763A

MXPA99010763A - Improved medical pump tubing

Info

Publication number: MXPA99010763A
Application number: MXPA/A/1999/010763A
Authority: MX
Inventors: K Lal Birendra; Tk Ling Michael; T Ryan Patrick; Qin Chuan; Woo Lecon; S Ding Yuanpang; L Rostron Donna; R Mizener Susan
Original assignee: Baxter International Inc
Priority date: 1998-05-26
Filing date: 1999-11-22
Publication date: 2000-09-04

Abstract

The present invention provides a method of using a medical tubing (10) with a pump for administering measured amounts of a beneficial fluid over time to a patient comprising the steps of providing a tubing (10) having a first layer (14) selected from the group consisting of ethylene homopolymers and ethylene copolymers, wherein the copolymers of ethylene are an ethylene monomer copolymerized with at least one monomer selected from the group consisting of lower alkyl olefins, lower alkyl esters of a carboxylic acid, and lower alkene esters of a carboxylic acid, the lower alkyl and lower alkene having from 3 to 18 carbons, the tubing having been exposed to a sterilization dosage of radiation of from about 15 to about 45 kGys;and pumping fluid through the tubing (10) with the pump.

Description

i • IMPROVED PERFORMANCE OF PIPING AND MEDICAL PUMP THROUGH IONIZED RADIATION DURING STERILIZATION DESCRIPTION OF THE INVENTION Technical Background This invention relates to a method for the manufacture of medical tubing and more particularly to a process for improving the performance of the tubing of a medical pump by irradiating the tubing and optionally also guiding the tubing.

BACKGROUND OF THE INVENTION In the medical field, where the beneficial agents are collected, processed and stored in containers, transported and finally released through tubes through an infusion to patients, there is a recent trend towards the development of materials useful for the manufacture of such containers and pipes without the disadvantages of the materials currently used as polyvinyl chloride. These new pipe materials must have a unique combination of properties, so that the pipeline can be used in fluid management devices and with medical infusion pumps. Among these properties are the REF: 31931 materials that must be optically transparent, environmentally compatible, that have a sufficient strength of performance, elasticity and flexibility, that have a minimum amount of low molecular weight additives and other extractive ones, and that are compatible with medical solutions. It is desired that the medical tubing be optically transparent to allow a visual inspection of fluids in the tubing, it is also desired that the tubing be optically and ultrasonically transparent to increase the compatibility of the tubing with the medical infusion pumps. medical devices are provided with ultrasonic sensors to detect abnormal conditions in the pipe such as air bubbles.It is also a requirement that the pipeline is compatible with the environment since a large amount of medical tubing is disposed of fill and through incineration For the ready-to-fill pipeline, it is desired to be used as a lightweight material as long as possible to manufacture the pipe.Additional benefits are realized by using a material that is thermoplastically recyclable so that the waste generated during manufacturing can be incorporated into virgin material and re-use in others Useful articles For pipes disposed by incineration, it is necessary to use a material that did not generate or minimize the formation of derivatives such as inorganic acids which can be harmful irritants and corrosive to the environment. For example, PVC can generate unacceptable amounts of hydrogen chloride (or hydrochloric acid when it makes contact with water) in the incineration. To be compatible with medical solutions, it is desired that the tubing material be free of or contain a minimum volume of low molecular weight additives such as plasticizers, stabilizers and the like. These components could be extracted by therapeutic solutions that come in contact with the material. The additives can react with the therapeutic agents or on the other hand they can provide an ineffective solution. This is especially annoying in biotechnology drug formulations where the drug concentration is measured in parts per million (ppm), instead of weight or volume percentages. Even minute losses of the biotech drug can give an unhelpful formulation. Because biotechnology formulations can cost several thousand dollars per dose, it is essential that the material in the pipeline be inert. Polyvinyl chloride ("PVC") has been widely used to make medical tubing since it meets most of these requirements. The PVC pipe is optically transparent to allow a visual inspection of the fluid flowing through it. PVC tubing has proven to work well in pump delivery devices. Medical PVC tubing also has desirable tensile strength characteristics so that the material can stretch to a certain degree along a longitudinal axis of the tubing without causing a significant permanent reduction in the diameter of the tubing. In other words, the PVC pipe is resistant to narrowing. PVC medical tubing also has favorable surface characteristics to allow control of the fluid flow rate through the tubing using sliding clamps which operate by bending the sidewall of the tubing to stop or reduce fluid flow to through the pipeline. The sliding clamp can be used without causing a nick or cut in the pipe.

Because PVC itself is a rigid polymer, low molecular weight components known as plasticizers must be added to give PVC flexibility. As indicated above, in some cases these "plasticizers can be extracted out of the pipeline by passing the fluid through the pipeline.Therefore, and due to the known difficulties in the incineration and recycling of PVC, there is a desire to replace PVC medical tubing Polyolefins and polyolefin alloys have been developed which meet various requirements of medical containers and pipes, without the associated disadvantages of PVC Polyolefins are normally compatible with medical applications because They have a minimal extractability of fluids.Most polyolefins are beneficial to the environment since they do not generate degrading damage in the incineration, and in most cases they are capable of being thermoplastically recycled.Several polyolefins have efficient costs in materials that can provide an economical alternative to PVC. There are, however, vari obstacles to overcome to replace all the favorable attributes of PVC with a polyolefin.

For example, problems have been found using certain polyolefins to make medical tubing. In such a pipe it has been found to have poor surface characteristics being quickly susceptible to cutting, notching or breaking when the pipe is clamped using a sliding clamp. Certain polyolefin pipes also present difficulties during use with pump pressurized delivery devices where the pump controls the flow velocity of the fluid through the pipe by consecutively impacting with the side walls of the pipe to release a precise amount of fluid over the pipe. a given period of time. Pumps that are used to infuse the beneficial agents to patients have several sensors to detect such conditions as the counter pressure of the fluid in the tubing, and air bubbles in the fluid stream. The sensors stop the pump from operating when it detects an unacceptable counter pressure or an air bubble. The sensors usually have a sensor body in which a segment of the pipe of the management device is secured on the site. It has been found that there is a tendency to deformation of the polyolefin pipe when it is placed in the sensor body due to the resistance with the side walls of the sensor housing. This deformation in some cases leads the detectors to indicate an abnormal condition and inappropriately shut down the infusion pump. Additionally, in certain polyolefin pipes it has been found that they have a low performance force. Because there is a direct relationship between the performance force and the module, it is very difficult to increase the performance force without increasing the modulus of the material at the same time. In polyolefin materials, the module is mainly dependent on crystallization. In PVC materials, the module is mainly dependent on the amount of plasticizer added. When the modulus of the polyolefin material is selected to equal the plasticized PVC, the yield strength of the polyolefin material becomes significantly reduced, and the resulting piping has a performance force too low to resist potentially external stretching forces that can produce efforts in the pipeline. Reciprocally, when the performance force is equalized with PVC the resulting module is too high to operate with pumps.

Polyolefin tubing exhibiting low resistance forces are rapidly susceptible to a phenomenon which is referred to as a narrowing. The narrowing is a localized reduction in the diameter of the pipe that occurs when stretching the pipe under moderate tension along the longitudinal axis of the pipe. The narrowing can cause a reduction in the flow of fluid through the pipeline so the performance of the pipe is inefficient. Applicants have found that it is possible to increase the resistance to pipe narrowing by pre-orienting the pipe along the longitudinal axis of the pipe. Nevertheless, the orientation process can lead to dimensional instability. In particular, the oriented polyolefin pipe experiences a phenomenon known as heat recovery, which is sometimes referred to as the "memory effect". Heat recovery is a complicated phenomenon that occurs when the oriented pipe is heated above the temperature reached during the orientation process. When this happens the pipe loses its orientation causing dimensional and contraction changes in the pipe. In addition, applicants have discovered that _ most medical lines suffer some permanent deformation when subjected to long periods (24 hours), repetitive, cyclic voltages introduced by pumping mechanisms such as Baxter's FLO-GARD® 6000 series pumps. . About this long period of use, the deformation causes a variation in the rate of release of the solution from the initial velocity. This is especially constant for polyolefin tubing with low crystallization. It has also been shown that polyolefin tubing has a low thermal stability during storage, transportation, and final applications. The low thermal stability of the polyolefin pipe can lead to changes in the desired dimensions and shapes. These dimensional changes and adversely can probably affect the accuracy of the volume of fluid released. It can also lead to changes in shape that can provide the pipe with incompatibility or difficulty of use with the pumps. A problem occurs when the pipe, which is frequently stored and shipped in a rolled state, arrives in a coiled form assembly. Thus, rolled tubing is difficult to use when it has the tendency to return to a rolled form.

A method for improving the thermal stability of non-PVC and polyolefin materials is shown in US Patent no. 4,465,487 issued by Nakamura et al. And assigned to Terumo Kabushiki Kaisha of Japan ("Nakamura"). Nakamura relates to a container for medical use produced from a polyolefin material. More particularly, Nakamura relates to a medical container produced from an ethylene-vinyl acetate (EVA) copolymer containing 10 to 35 weight percent crosslinked vinyl acetate using a supplied electron beam of 50 to 200 kGys to achieve an EVA copolymer having a gel content of 50% or more. (Column 3, lines 40-46). The material is joined transversely so that the container can withstand the temperatures reached during steam sterilization. However, the high gel content resulting from the material caused by a high radiation dose gives the material by nature a thermostability, and thus, the Nakamura container material probably can not be recyclable by conventional means. Others have provided pipes that are not PVC with multiple layers. For example in the North American Patent no. 5,562,127 a chlorine-free multilayer pipe material having an inner thermoplastic layer having a young modulus of about 2 to about 60 MPa and an outer layer having a young modulus of equal to up to about seven times the young modulus is disclosed. of the inner layer. (Column 2, line 33-column 3, line 8). The outer layer provides hardness and abrasion resistance according to received reports. (Column 2, lines 62-64). However, without the special process conditions the pipeline is likely to be too stiff to be compatible with medical infusion pumps such as Baxter's FLO-GARD®. Therefore, there is a need for a medical tubing produced from a polyolefin material having a thermoplastic nature and the desirable characteristics of PVC materials without the extraction of plasticizers.

SUMMARY OF THE INVENTION The present invention provides a method for improving the performance of the pipe when used with a pump by exposing the pipe to radiation levels of sterilization to improve the elasticity and flexibility of the pipe. The polymeric material used to produce the pipeline is provided in low-level doses of radiation supplied by an electron beam or cobalt-60 gamma sources during the sterilization process. The dosage of the radiation is preferably less than 50 kGys in the order of 15 kGys to 45 kGys. Such low-level radiation dosages allow one to achieve a low gel content. Thus, the elasticity and flexibility of the pipe is reinforced while the pipe remains a thermoplastic able to be recycled or reprocessed. The present invention further provides a pipe manufacturing method that provides an optional additional step of orienting the pipe along a longitudinal axis. The pipe can be oriented along the longitudinal axis to reduce the diameter of the pipe to define an oriented diameter, and applying heat to the pipe oriented to heat the pipe assembly and maintain dimensional stability of the pipe. Preferably the initial diameter is 10% to 300% greater than the oriented diameter. Preferably the step of orienting the pipe can be done in a wet or dry process. Each orientation process shares the steps of extending the pipe between a first extractor and a second extractor spaced apart by a distance and controlling the relative speeds of the first and second extractors so that the draw rate of the second extractor is greater than that of the first extractor to guide the pipe between them. In the wet process of orientation, the pipe is passed through an aqueous bath during the orientation stage and the pipe is not in the dry process. The present invention is additionally provided for the thermosetting of the pipe and overcoming the memory effect discussed above.The thermosetting process includes the step of exposing the pipe to a temperature higher than the pipe would normally be exposed during shipping, storage, and use, but below the temperature where the pipe is completely melted, exposing the pipe at temperatures higher than the application temperature, melting the lower melting crystals, less requested, leaving the high melting crystals They will be thermally stable above the range of the application temperature.The part of the highly oriented macro molecule chains will also relax at thermosetting temperatures to produce a pipe with good thermal stability.The thermosetting step includes the steps of heating the pipeline after the orientation stage in the hot water bath. Preferably, the pipe is not oriented during the heating step but is retained under sufficient tension to prevent the pipe from loosening. It is also possible to allow the pipe a slight relaxation so that the pipe can loosen slightly. It is also preferable that the pipe be supported with a structure to prevent or minimize the additional orientation of the pipe. In addition, it is desirable to position a plurality of spaced rollers in the hot bath. The pipeline specializes on the rollers to define a serpentine model for the pipe to perform several longitudinal steps through the hot bath. It may be desired to motorize these rollers. The present invention provides a monolayer pipe of ethylene-vinyl acetate copolymer which is exposed to dosages of radiation sterilization to increase the performance of the pump. The present invention also provides a multi-layer pipe. In a preferred form the pipe has an outer layer of ethylene-vinyl acetate and an inner layer of homopolymers and copolymers of alpha-olefins. Preferably, the modulus of elasticity of the EVA is smaller than that of the material of the inner layer.

The multi-layer pipe can also be larger than two layers, such as three layers. Multilayer pipes will have an outer layer, a central layer and an inner layer. In a preferred form the outer layer is softer than or has a modulus of elasticity less than that of the inner layer.

Brief Description of the Drawings Figure 1 is an enlarged cross sectional view of a monolayer medical tubing of the present invention; Figure 2 is an enlarged cross-sectional view of a multi-layer pipe of the invention; Figure 2a is an enlarged cross sectional view of a multi-layer pipe of the invention; Figure 3 is a schematic representation of the method for forming, orienting and thermosetting medical tubing; Figure 3a is a plan view of a serpentine model where the pipe can perform a cooling or heating bath of the process shown in Figure 3; Figure 3b is a schematic representation of a method for forming, dry orienting and thermosetting medical tubing; Figure 4 is a schematic of a method of pumping fluid through the polymer tubing; Figure 5 is a cross-sectional view of a polymer tubing during ascent in a pumping operation; Figure 5a is a cross-sectional view of a polymer pipe during a descent in a pumping operation; Figure 5b is a cross-sectional view of a polymer tubing prior to multiple compressions with a pump; Figure 5c is a cross-sectional view of a polymer tubing after multiple compressions with a pump; Figure 6 is a graphical representation of the relationship between pumping accuracy and radiation dosing of cobalt-60 gamma; and Figure 7a is a graphical representation of the relationship between pumping accuracy and dosing of electron beam radiation.

Figure 7b is a graphic representation of the relationship between pumping accuracy and gamma radiation dosage. Figure 8a is a graphical representation of the correlation between the modulus of elasticity and the yield strength with varying dosages of electron beam radiation. Figure 8b is a graphical representation of the correlation between the modulus of elasticity and yield strength with varying dosages of gamma radiation.

Detailed description While the invention is susceptible to modality in different forms, the preferred embodiments of the invention will be described in detail in the drawings and the present invention will be described in detail with the understanding of which the present description will be considered as an exemplification of the principles of the invention. invention and will not be thought to limit the broad aspect of the invention to the illustrated embodiments.

I. Modified Radiated Polymer Medical Tubing Figure 1 shows the structure of the tubing 10 having a side wall 12. Preferably the side wall of the tubing is made of a polymeric material of an ethylene copolymerized with comonomers selected from the group consisting of lower alkyl olefins, and lower alkyl and lower alkene substitute the carboxylic acids, the ester and the anhydride derivatives thereof. Preferably, the carboxylic acids have from 3 to 10 carbons. The carboxylic acids include, acrylic acid and butyric acid accordingly. The term "lower alkene" _ and "lower alkyl" means to include a carbon chain having 3-18 carbons, more preferably 3-10 and more preferably 3-8 carbons. Preferably, the pipe is an ethylene and vinyl acetate copolymers having a vinyl acetate content of at least about 36% by weight, more preferably at least about 33% by weight and most preferably at least about 33% by weight. or equal to approximately 28% by weight. It is also preferred that the EVA have a high molecular weight and a melt flow index measured by ASTM D-1238 of at least 5.0 g / 10 minutes., more preferably at least about 1.0 g / 10 minutes and more preferably at least 0.8 g / 10 minutes or any interval or combination of intervals therein. It may also be desirable to mix in the material of the pipe certain amounts of resin mixed with a polyolefin and more particularly with homopolymers and copolymers of alpha olefins. These additives can be mixed in the pipe material in an amount of 5% to about 95% by weight of the pipe material. The alpha olefins may contain from 2 to about 20 carbon atoms or any range or combination of ranges therein. The alpha olefins more preferably contain from 2 to about 10 carbon atoms. Thus, olefin polymers can be derived from olefins such as ethylene, propylene, 1-butene, 1-pentene, 4-methyl-1-pentene, 1-octene, 1-decene, 4-ethyl-1-hexene, etc. ., or mixtures of two or more of these olefins. Examples of particularly useful olefin polymers include ethylene-butene copolymers and ethylene-propylene copolymers and octene-1 and ethylene copolymers which will be referred to as ultra low density polyethylenes (ULDPE). ULDPE's have a density preferably equal to or less than 0.910 g / cm3 and are preferably produced using metallocene catalyst systems. Such catalysts are "single site" catalysts because they have a single electronically and spatially equivalent catalyst position as they are opposed to Ziegler-Natta type catalysts which are known to have multiple catalyst sites. The metallocene catalyzed ethylene alpha olefins are marketed by Dow under the trade name AFFINITY and by Dupont-Dow under the trade name ENGAGE, and by Exxon under the trade name EXACT. It may be desirable to add a radiation sensitive additive to the pipe material that is sensitive to radiation exposure such as gamma rays, electron beam, ultra violet light, visible light or other sources of ionizing energy. Suitable radiation-sensitive additives include organic peroxides such as dicumyl peroxide (DiCup) and other free radical generating compounds. Other sensitive functional groups of free radicals include acrylate, acid, dienes and their copolymers and terpolymers, amide, amine, silane, urethane, hydroxyl, epoxy, ester, pyrollidone, acetate, carbon monoxide, ketone, imidazoline, photo and UV initiators , fluorocompounds, etc. These functional groups can be in polymeric and non-polymeric compounds. More particularly suitable additives include ethylene-vinyl acetate, ethylene-methyl acrylate (AME), ethylene-acrylic acid (EAA), fatty amides, functionalized and non-functionalized styrene-butadiene copolymers of low viscosity and their hydrogenated derivatives, polybutadiene, polyisoprene, terpolymer of ethylene-propylene-diene monomer, polybutene, urethane acrylate, epoxy acrylate, photoinitiators, etc., functionalized and non-functionalized. Still, more particularly the additives include low viscosity low functionalized density polyethylene, functionalized with epoxies, carboxylic acids and their ester and anhydride derivatives, AC polymers by Allied Signal, SR / CN and Esacure products from Sartomer, functionalized fat products of Akzo Nobel and Henkel, Ciba-Geigy photoinitiators, 3 M fluoro compounds, DuPont EVA, Dow Chemical AAE and Chevron AME and 1,2-syndiotactic polybutadiene from Japan Synthetic Rubber Co. The ethylene-propylene terpolymers have a third component of an unconjugated diolefin chain, for example, 1,4-pentadiene, 1,4-hexadiene, 1,5-hexadiene or a cyclic polyene, for example, dicyclopentadiene, methylenenonbornene, ethylideneorbornene, cyclooctadiene, methyltetrahydroindene, etc. These types of additives will be called EPDM. The appropriate EPDMs are marketed under the trade name NORDEL (Dupont Chemical Company), VISTALON (Exxon), KELTAN (Dutch State Mines), JSR (Japan Synthetic Rubber) and EPDM from Mitsui Chemical Company. The radiation sensitive additives should be added to the pipe material in effective amounts preferably in an amount by weight of the monolayer or outer layer of 0.01-20.0%, more preferably 0.01-10.0% and more preferably 0.02-5.0%. Optionally, the pipe material can be further modified by incorporating polar additives to improve its compatibility with adhesives such as cyanoacrylate adhesives and improve other surface characteristics such as friction (lubrication). The polar additives are preferably selected from a non-polymeric aliphatic or aromatic hydrocarbon having more than 5 carbon atoms but less than 500, more preferably less than 200 carbons and more preferably less than 100 carbons in the structure. Additionally, the additives must have negative electron groups selected from the group of amines; amides; hydroxyls; acids; acetate; ammonium salts; organometallic compounds such as metal alcoholates, metal carboxylates, and metal complexes of numerous 1,3-dicarbonyl compounds; phenyl phosphines; pyridines; pyrrolidones; imidazoline, and oxazolines. The modification of the additive may also be an emulsion or polymer solution. The polar additives should be included in a quantity by weight of the pipe material of about 0.001% - 10.00%, more preferably 0.01-2.0%. Figure 2a shows a multilayer pipe having an outer layer 12, an inner layer 14 and a central layer 15. In a preferred form, the outer layer 12 and the core layer 15 are made of the same material and additives as indicated previously for the pipe materials. The outer and central layers 12 and 15 do not have to be of the same material with each other. Preferably the inner layer 14 or the contact solution layer is selected from homopolymers and copolymers of alpha olefins. More preferably the inner layer 14 of polyolefin is a copolymer of ethylene with alpha olefins having from 3-18 carbons and more preferably from 4 to 8 carbons and most preferably is a ULDPE. Preferably, the inner layer has a minimum amount of components that are capable of migrating --- in a solution that passes through the pipe 10. Also, the outer layer 12 must have a modulus of elasticity less than that of the inner layer 14. In a preferred form, the core layer 15 will be the thickest layer and will constitute 55-99%, more preferably 75-99% and most preferably 90-98% of the total thickness of the wall or any range or combination of intervals in them. In a two-layer pipe structure shown in Figure 2, preferably the outer layer 12 must be thicker than the inner layer 14. Preferably the inner layer will have a thickness in the range of 1-40%, more preferably 1- 25% and more preferably 2-10% of the total thickness of the wall or any interval or combination of intervals therein.

II. Mixing Method The components of polymer blends should be mixed through a molten mixture, physical mixing such as damped mixing, or other means such as reactive extrusion.

III. Medical Tubing Manufacturing Method The medical tubing 10 of the present invention should have an internal diameter dimension within the range of 0.01-1.02 cm (0.003-0.4 inches), and a dimension of the outer diameter within the range of 0.30-1.27. cm (0.12-0.50 inches). More particularly, the medical tubing for use in administering the fluid using a medical infusion pump, such as the Baxter infusion pump marketed under the trade name FLO-GARD®, and COLLEAGUE®, having an internal diameter within the range of 0.25-0.27 cm (0.099-0.105 inches), an outside diameter within the -interval of 0.34-0.37 cm (0.134-0.145 inches), and a wall thickness within the range of 0.05-0.05 cm (0.018-0.021 inches) ). The pipe must be flexible and have a modulus of elasticity of less 50,000 psi, more preferably at least 30,000, more, still preferably at least 10,000 and more preferably at least 4,000 psi, or any range or combination of intervals in them.

IV. Heat Adjustment Method and Pipe Orientation Optionally, it may also be desired that the pipe 10 be oriented along its longitudinal axis and placed in this heat use dimension. This orientation step increases the yield strength of the pipe in the longitudinal direction with which the tendency of the pipe to narrow during use is reduced / Indeed, the preorientation of the pipe increases the resistance to the additional narrowing. Preferably, the pipe 10 should be oriented so that the initial internal and external diameters of the pipeline are anywhere from 10% -300% greater than the diameter of the pipe 10 after orientation and more preferably from 20% -120% and more preferably 30% -100%. These intervals additionally include all combinations and sub-combinations of intervals therein. The ratio of the initial diameter to the diameter after orientation will be referred to as the orientation ratio. The orientation process can be a wet or dry orientation process as indicated below. Figure 3 shows a schematic representation 30 of the orientation method of the pipe 10 and a wet orientation process. The wet orientation method includes the steps of providing a pipe 10, and orienting the pipe 10 along its longitudinal axis so that the pipe 10 has a desired inner and outer diameter, as specified above in Section III, and in the proportion of orientation. It is believed that the orientation step aligns the pipe molecules along the longitudinal axis to increase the resilience to the subsequent longitudinal tension force. The pipe 10 is then heated to reduce the shrinkage of the pipe and. fix the 'pipe in the dimension oriented. The pipe 10 (which can be single layer or multiple layers) is stretched in the direction indicated by the arrows 34 along a continuous path that can be referred to as a line. The term "upper line" shall refer to the locations along the line in an opposite direction to the direction of flow of the pipe 32. Reciprocally, the term "lower line" shall refer to the locations in the direction of the pipeline. pipeline flow. Using the term "line" should not be thought that the method should be carried out in a straight line, rather the means should be taken for the method to be carried out. out in a sequence of consecutive steps.

As shown in Figure 3, the pipe 10 is formed with an extruder 36. The pipe 32 exiting the extruder 36 preferably has a dimension of the outside diameter which will be 10% -300% greater than after the orientation and more preferably of 20% -120%, and more preferably 30% -100%. The pipe 10 is pulled from the extruder 36 with a first extractor 37, a second extractor 38, a third extractor 39, and a fourth extractor 40. The diameter of the pipe in the first extractor 37, when the pipe is in a solid state, it will be referred to as the initial diameter. The extractors 37, 38, 39 and 40 can have a silicone or rubber coating to increase the coefficient of friction with the pipe 32. The second and third extractors 38 and 39 can have a plurality of circumferentially extending and axially spaced slots for accommodating more than one set of pipe 32 on a surface of the extractors 38 and 39 at a time. - After exiting the extruder 36, the pipe 32 which is in a molten or semi-molten phase, passes through a first cooling bath 41 where the pipe 32 is cooled with air or liquid .. Preferably, the first cooling bath 41 is a water bath at a temperature within the range of 4 ° C-45 ° C. The pipe must be converted to a solid phase in the cooling bath 41. After leaving the first cooling bath 41 the pipe 10 extends between the first and second extruders 37 and 38 where the pipe 10 is oriented by operating the. second extractor 38 at a higher rate of speed than that of the first extractor 37 to achieve the desired orientation ratio. It is believed that by orienting the pipe while in the solid state it is more efficient to achieve an oriented pipe than to stretch the pipe immediately after it leaves the extruder 36 or when it passes through the first cooling bath 41 while the pipe is in a molten phase. or semifundida. This section of the line will be referred to as the orientation section 42. Preferably the second extractor 38 is operated at a speed within the range of approximately 4-10 times faster than that of the first extractor 37. Controlling the relative speeds of the first and second Extractors 37 and 38 one can control the internal and external diameters of the pipe 10 and achieve the desired orientation ratio. In the orientation section 42, the pipe 10 is passed through a second cooling bath 43 where the pipe 10 is cooled with air or liquid.

Preferably, the second cooling bath 43, as the first cooling bath 41, is an aqueous bath at a temperature within the range of 4 ° C-45 ° C. To overcome the memory effect of the oriented pipe 10, it is necessary to heat the pipe to a temperature above what would normally be exposed during shipping, storage and use, but below the temperature at which the pipe completely melts. By exposing the pipe at temperatures above the application temperature, the lower melting crystals are melted less frequently, leaving the higher melting crystals which will be thermally stable over the application temperature range. The portion of the highly oriented macromolecule chains will relax to provide a pipe with improved thermal stability. For this purpose, after leaving the second cooling bath 43, the pipe 10 is directed over the second extractor 38 and extends between the second extractor 38 and the third extractor 39. The pipe 10 advances in an opposite direction towards the extruder 36. and through a heating bath 44 where the pipe is heated. Preferably, the heat bath 44 is positioned on the second cooling bath 43 to save floor space. However, this positioning is optional. This portion of the process will be referred to as thermosetting section or step 45. Preferably, the thermosetting step 45 is done online after the orientation section 42, but could be done offline in a batch process. During the thermosetting step 45, the pipe 10 is passed through a heating bath 44 where the pipe 10 is heated with a medium such as air or hot liquid. The heating bath 44 is preferably an aqueous solution of water at a temperature between about 50-99 ° C. Additives such as salt can be added to the aqueous solution. In order to control the dimension of the pipe, it is desired that the pipe 10 is not oriented during the heat curing stage 45. For this reason the pipe 10 must be kept under minimum tension to keep the pipe shown or the pipe must be allowed loosen a quantity, between the second and third extractors 38 and 39, to prevent or control the contraction. Thus, the second and third extractors 38 and 39 could be operated at similar speeds or the extractor 39 could be operated at a speed slightly lower than that of the extractor 38 to fix some shrinkage. To further prevent the orientation of the pipe 10. In the thermosetting section 45, it may also be desirable to support the pipe 10 while it is pulled through the heating bath 44 with a support structure 47. However, it is optional to provide the support structure 47. The structure of Suitable holder 47 includes a conveyor that moves at the same speed ratio while the pipe 10 passes through the heat setting section 45. Another support structure 47 is a plastic or metal conduit having a diameter greater than of the pipe where the pipe 10 is supported by the inner surface of the conductor After leaving the heating bath 44, the pipe 10 it extends between the third extractor 39 and the fourth extractor 40. The extractor 40 must be operated at a speed similar to or slightly lower than that of the extractor _39 to prevent further orientation. The pipe 10 is again passed through the second cooling bath 43. Of course, it is possible to maintain a separate cooling bath, but this arrangement saves floor space.

It may also be desirable to maintain the pipe 10 making several longitudinal passages through the cooling bath 43 or the heating bath 44 as shown in Figure 3a to provide maximum cooling or heating to the pipe in a minimum amount of space. This can be achieved by providing a plurality of rollers 49 spaced apart to define a serpentine pattern-through the heating bath 44 or the cooling bath 43. To prevent any further orientation of the pipe 10, it may be necessary to operate the fourth extractor 40 a a similar speed or a slightly lower speed ratio than that of the third extractor 39. After passing the fourth extractor 40, the pipe has an oriented diameter and passes through a cutter or winder 48 where the pipe 10 is cut to the Appropriate length or wrap over the wire feeder for storage or shipping. Figure 3b shows a dry orientation process 30. The dry orientation process is the same in most respecting the wet orientation process with the major exception that the pipe 10 is oriented in section 42 between the extractors 37 and 37a. The extractor 37a is operated at a speed greater than that of the extractor 37. During the dry orientation step 42, the pipe 10 is not submerged in the aqueous bath 43 as is the case in the wet orientation step 42. In the process of wet orientation, the extractors 38, 39, and 40 will run at a speed similar to or lower than that of the extractor 37a. Despite these differences between dry and wet orientation processes, it is desirable that the pipe be oriented while in the solid state.

V. Method of Pipe Irradiation During the course of the development of the medical device, more medical devices have to be sterilized. Sterilization by means of radiation is a preferred method. Surprisingly, it has been found in this investigation that by exposing the tubing to normal sterilization doses of radiation, the performance of the tubing was improved while the accuracy of the fluid dose release was measured. As shown in Figures 7a and 7b, pumping accuracy was increased with increased doses of electron beam radiation (Figure 7a) and gamma radiation (Fig. 7b). As shown in Figures 8a and 8b, it was also found that the modulus of elasticity of the pipe, line 80, decreases with increased doses of an electron beam (Figure 8a) and dose of gamma radiation (8b). It was surprising that these decreases in the module were not accompanied by a significant decrease in the performance strength of the pipeline as indicated by line 82. The sterilization radiation is normally carried out at many lower doses of radiation that are used for crosslinked polymers. The normal magnitude of such sterilization radiation is in the order of about 25 kGys, but sometimes it can be as low as 15 kGys. In some cases, although not necessarily, exposing the pipe to radiation sterilization produces a measurable change in the gel content of the pipe. The gel content indicates the weight percentage of insolubles to the weight of the pipe material. This definition is based on the well accepted principle where crosslinked polymer materials are not dissolvable. However, the content Important gel ~ such as approximately 50% give the material a thermostability. Such thermostabilities are undesirable for medical uses when they are not capable of being recycled using normal recycling techniques.

It is important to note that it is possible to expose pipes to radiation sterilization doses and achieve the elaboration of reinforced piping with pumps without observing any change in the gel content of the pipe. The medical tubing 10 of the present invention shows a gel content that preferably ranges from 0% to 49.9%, more preferably 0% to 45%, and more preferably 0% to 40%, or any range or combination of ranges therein. Preferably, the pipeline is exposed to a lower dose of gamma radiation ranging from 15 kGys to 58 kGys, more preferably 15 kGys to 45 kGys, and more preferably 15 kGys to 35 kGys, or any range or combination of intervals therein. Thus, this pipe 10 maintains its thermoplastic characteristics and can be reprocessed or recycled using normal recycling techniques. Pumping accuracy can also be improved after the lower doses of radiation when various amounts of minutes - of the radiation sensitive additives described above are added to the polymeric material prior to extrusion. An example of a pump in which an improvement in pipe making has been observed is FLO-GARD® 6201. FLO-GARD® 6201 is a simple, electromechanical, positive-pressure, peristaltic, intravenous pump head of the infusion device. The pump is designed to operate with normal PVC intravenous tubing that conforms to Baxter specifications. The pump has a primary flow rate range of 1 to 1999 ml / hr. The secondary range is 1 to 999 ml / hr, or the upper limit will be the same as the limit of the primary velocity, which may sometimes be lower. The infusible volume for both secondary and primary modes is 1 to 9999 ml. This pump has the ability to operate with a wide variety of I.V. 'including: basic devices, filter devices, CONTINU-FLO®, and BURETROL® devices. Pumping accuracy shall be within j ^ lO% for any flow rate maintained for 24 hours of continuous service using the same I.V. As described in Figure 4, the pump has a series of eight "tabs". The tabs provide positive pressure to squeeze the fluid out of the pump segment to release it to the patient. The eight tabs move up and down in sequence and perform a peristaltic infusion function. During this process, the pipeline undergoes repetitive cyclic deformations that in the future can cause permanent deformation in the -geometry of the pipe. (See Figures 5b and 5c). This permanent deformation (See Figures 6 and 7) leads to a volumetric reduction in the tubing which, in turn, causes a low release of fluid to the patient. Such a phenomenon is generally referred to as "fall pumping". The following examples will show that the pipe of the present invention had less changes in the flow rate over a period of 72 hours when compared to a pipe sterilized without radiation and the medical PVC pipe being. The illustrative examples do not. limit the pipes of the one indicated below. The other numerous examples can easily be contemplated in the clarity of the main guides and techniques contained therein. The examples given therein illustrate the invention and not in any sense to limit - the manner in which the invention can be practiced.

SAW. Examples Examples of Radiation Sterilization Experiments in the accuracy of fluid release with electromechanical pumps, gel content and relaxation time were directed to characterize the properties of the irradiated piping. The gel content was determined by solvent extraction. Pipe samples were removed by reflux in a Soxhlet extractor with a 150 mesh stainless steel screen and 250 ml of xylene for 6 to 8 hours, sufficient for a complete extraction of soluble polyolefin materials. The residual materials on the screen were dry under vacuum at a constant weight which was used to calculate the gel content: Gel% = [residual weight / sample weight] x 100% Relaxation time (ie, the time to force to deteriorate at 1 / e (36.8%) of the initial force under the constant tension velocity) at high temperature is another way to re-measure elastically the polymeric materials. The test procedure is described as follows. A Rheometrics Solid Analyzer RSA-II was used for the study. A pipe that is not PVS (OD approximately 0.361 (0.141 inch)) is cut to approximately 2.54 cm (1 inch) in length. A two-plate figure is heated for 20 minutes at approximately 75 ° C, before the pipe is 2.54 cm (1 inch) in length, inserted between the two metal disks (approximately 1.51 cm (0.595 inch) in diameter). The initial opening between the two disks is approximately the same as the OD of the pipe (ie, '0.36 cm (0.141 inch)). The pipe and plates are then heated to 75 ° C for another 5 minutes before compressing the pipe to a constant tension. The initial force and the force of decay are recorded with time. The relaxation time is taken as the point when the force decreases to 1 / e or 36.8% of the initial force value. As shown in the following examples, minor increases in relaxation time appear to improve pumping accuracy. 1. Example 1 Separate pipes made of 100% ethylene-vinyl acetate (EVA) (DuPont ELVAX) and a mixture of EVA and Ethomeen 0/15 (0.23 by weight) (Akzo Nobel Chemical Company) were irradiated at various radiation levels . The mode of radiation provided was cobalt-60 gamma. Each length of tubing was then used in conjunction with a Flo-Gard® 6201 medical infusion pump marketed by Baxter -Healthcare Corporation as described in detail above. The change in the flow velocity of the pump through the pipe is measured after 72 hours of continuous use. The Flo-Gard® 6201 is a simple pump head, positive electromechanical, peristaltic, intravenous, infusion device. The pump is designed to operate with normal PVC intravenous tubing which conforms to Baxler specifications. The pump has a primary flow rate range from 1 to 1999 ml / hr. The infusible volume for both secondary and primary modes is 1 to 9999 ml. This pump is capable of operating with a wide variety of normal management devices including: basic devices, filter devices, Continu-Flo®, and-Buretrol® devices. Pumping accuracy must be within + 10% for any flow rate adjustment for 24 hours of continuous service using the same management device. As described in Figure 4, the pump has a series of eight "tongues". The tabs provide positive pressure to squeeze the fluid out of the pump segment to release it to the patient. The eight tabs move up and down in sequence and form a peristaltic infusion function. During this process, the pipe undergoes repetitive cyclic deformations that in the future can cause permanent deformation in the geometry of the pipe. (See Figures 5 and 5a). This permanent deformation (See Figures 6 and 6a) leads to a volumetric reduction in the pipe which, in turn, causes a low release of fluid or pumping fall. If the material used to make the pipe has no similar elasticity and drags strength properties like the current PVC material, high deformation can occur. This high deformation of the pipe would cause a greater low release of the preset flow rate compared to the PVC pipe. Dropping pumping generally decreases with increased levels of radiation dose of cobalt-60 gamma. The level of radiation and changes in fluid release for Example 1 are indicated below in Table 1.

Table 1 2. Example 2 Separate monolayer pipelines, manufactured from a mixture of 95% EVA and 5% ULDPE, were treated with different amounts of a precomposite additive, dicumyl peroxide (DiCup). The pipes were then irradiated with escalating doses of cobalt-60 gamma radiation. Finally, the pipes were corked in a FLO-GARD® 6201 infusion pump, and the percentage change in the flow velocity released through the pipes was moderate.

The level of additive, the dosage of the radiation, and the corresponding change in the performance of the pump are indicated below in Table 2.

TABLE 2 3. Example 3 In Example 3, the elaboration of mainly EVA tubing was irradiated with different doses of radiation provided by an electron beam. Table 3 below shows the change in pumping accuracy at different levels of a radiation dose of the electron beam.

TABLE 3 4. Example 4 In Example 4, the fabrication of the EVA pipeline was mainly irradiated with different doses of radiation provided by Cobalt-60 Gamma radiation. Table 4 below shows the change in pumping accuracy at different levels of the radiation dose of Cobalt-60 gamma.

TABLE 4 . Example 5 In Example 5, the present gel contained in the manufacture of mainly EVA pipes measured after the pipeline was irradiated at progressively higher doses of cobalt-60 gamma radiation. The gel content increased appreciably over 50 kGys of radiation. In low doses of radiation, it is known that the gel content could be maintained at imperceptible levels. However, the relaxation time for these pipe samples still increased. Thus, the pipe is maintained as a thermoplastic instead of a thermal apparatus.

TABLE 5 6. Example 6 This example shows that the addition of very small amounts of dicumyl peroxide can increase the gel content at the same radiation level of cobalt-60 gamma. The results are indicated later in table 6.

TABLE 6 7. Example 7 In Example 7, five samples are mainly comprised of EVA that were irradiated with five different radiation levels of an electron beam. The gel content present in each of the samples was measured subsequent to the radiation sterilization process. Higher gel volumes were observed while the radiation dose was increased. Table 7 summarizes the results of the experiment.

TABLE 7 8. Example 8 In Example 8, the relaxation time was measured as a function of the radiation dose of cobalt-60 gamma. At present, five pipe samples comprised mainly of EVA were irradiated with five different levels of cobalt-60 gamma radiation. ~~ The relaxation time was measured for each sample. The experiment revealed that the relaxation time could be increased by normal doses of cobalt-60 gamma sterilization radiation. It can be seen how the relaxation time increases, the fall pumping decreases, and therefore the pumping accuracy increases. The results of this experiment are indicated in table 9.

TABLE 9 9. Example 9 The relaxation time was also measured as a function of the radiation dose of cobalt-60 and the level of additive. Table 10 shows that the addition of several small amounts of dicumyl peroxide has increased relaxation times compared to samples that have lower levels of dicumyl peroxide after the samples were irradiated with identical doses of cobalt sterilization radiation -60 gamma.

TABLE 10 . Example 10 The relationship between the relaxation time and the increased radiation doses of the electron beam is summarized in Table 11. Six pipe samples composed mainly of EVA were irradiated to six higher doses of electron beam radiation. When the radiation dose is increased, the relaxation time increased. The increase in relaxation time associated with the increase in electron beam radiation was much greater than the increase in relaxation time associated with similar radiation levels of cobalt-60 gamma, (See Table 11.) TABLE 11 Pipes were made with the materials indicated in table 12 and exposed to several doses of gamma radiation. The modulus of elasticity was measured to determine the effects of radiation on the modulus of elasticity. The module was measured with an Instron 4201 at room temperature (40.53 ° C (73 ° F) / 50% relative humidity) at a speed of 20 in / min with a measuring length of 5.08 cm (2 inches).

TABLE 12 11. Example 11 In Example 11, multilayer pipes having an outer layer of CM576 (EVA) and an inner layer of SM8250 or SM 8401 (ULDPE) were made. Pipe samples were exposed to several doses of a Cobalt-60 gamma source as indicated in Tables 13-14. The pipes were tested for compatibility with a Baxter FLO-GARD® 6201 pump (Table 13). The pipes were also studied to determine the relationship between the yield strength and the modulus of elasticity with increased doses of radiation exposure of Cobalt-60. As shown in Table 14, when the radiation dose was increased the modulus of elasticity of the pipe decreased significantly with only a slight change in the strength of resistance (Also see Figures 8a and 8b).

TABLE 13 While the specific embodiments have been illustrated and described, numerous modifications are possible without departing from the spirit of the invention, and the scope of protection is only limited by the scope of the accompanying claims. It is noted that in relation to this date, the best method known to the applicant to carry out the aforementioned invention, is the conventional one for the manufacture of the objects or products to which it refers. Having described the invention as above, it is claimed as a priority what is contained in the following:

Claims

'CLAIMS

1. A method of use for a medical tubing with a pump for administering measured quantities of a beneficial fluid over time to a patient characterized in that it comprises the steps of: providing a tubing having a first layer selected from the group consisting of ethylene homopolymers and ethylene copolymers, wherein the ethylene copolymers are an ethylene monomer copolymerized with at least one monomer selected from the group consisting of lower alkyl olefins, lower alkyl esters of a carboxylic acid and lower alkene esters of an acid carboxylic, each of the lower alkyl and the lower alkene has 3-18 carbons, or mixtures thereof; the tubing has been exposed to a dose of radiation sterilization from about 15 to about 45 kGys; and pumping the fluid through the pipe with the pump.

2. The method according to claim 1, characterized in that the pipe is an ethylene-vinyl acetate copolymer having a vinyl acetate content of not more than 36% vinyl acetate by weight of the copolymer.

3. The method according to claim 2, characterized in that the gel content of the ethylene-vinyl acetate copolymer is about 0-49%.

4. The method according to claim 2, characterized in that the ethylene-vinyl acetate copolymer has a melt flow index of less than about 5.0 g / 10 minutes.

5. The method according to claim 2, characterized in that the ethylene-vinyl acetate copolymer has a melt flow index of less than about 1.0 g / 10 minutes.

6. The method according to claim 2, characterized in that the ethylene-vinyl acetate copolymer has a melt flow index of less than about 0.80 g / 10 minutes.

7. The method according to claim 1, characterized in that the step of exposing the pipe to radiation sterilization dose comprises the step of exposing the pipe to a radiation source selected from the group consisting of gamma rays, ultra violet rays, and beam of electron.

8. The method according to claim 1, characterized in that the step of providing a pipe further includes the step of providing a pipe with a second layer concentrically disposed within the first layer of the pipe.

9. The method according to claim 8, characterized in that the second layer has a modulus of elasticity which is greater than ~ the modulus of elasticity of the first layer.

10. The method according to claim 9, characterized in that the second layer is selected from homopolymers and copolymers of the alpha-olefins. .

11. The method according to claim 10, characterized in that the second layer is an ultra-low density polyethylene.

12. The method according to claim 1, characterized in that the lower alkyl group and the lower alkene group have 3-10 carbons.

13. The method according to claim 1, characterized in that the first layer of the pipe additionally comprises a mixed resin of a polyolefin or polyolefin copolymers in an amount by weight of 5-95%.

14. The method according to claim 13, characterized in that the blending of polyolefin copolymer resin is an ultra-low density polyethylene.

15. The method according to claim 1, characterized in that the pipe includes a radiation sensitive additive.

16. The method according to claim 15, characterized in that the radiation sensitive additive is selected from a compound containing at least one functional group selected from the group consisting of organic peroxides, acrylates, acids, amides, amines, silanes, urethanes , hydroxyls, epoxies, esters, pirolidones, acetates, carbon monoxides, ketones, imidazolms, photo initiators, fluoro compounds, and dienes.

17. The method according to claim 16, characterized in that the additive sensitive to radiation is a dicumyl peroxide.

18. The method according to claim 16, characterized in that the compound having a diene functional group is an EPDM.

19. The method according to claim 16, characterized in that the functional group diene is a syndiotactic of 1,2-polybutadiene.

20. The method according to claim 16, characterized in that the diene functional group is a styrene-butadiene block copolymer.

21. The method according to claim 1, characterized in that the pump is a peristaltic pump.

22. A method of use for medical tubing with a pump for administering measured quantities of a beneficial fluid over time to a patient characterized in that it comprises the steps of: providing a multilayer tubing containing a first layer and a second layer, the first layer of a copolymerized ethylene monomer with at least one monomer selected from the group consisting of lower alkyl esters of a carboxylic acid and lower alkene esters of a carboxylic acid, lower alkyl and lower alkene each have 3-10 carbons, the second layer of homopolymers and copolymers of alpha olefins, the second layer is arranged concentrically within the first layer and has a modulus of elasticity greater than a modulus of elasticity of the first layer, the pipe has been exposed to a dose of radiation sterilization. from approximately 15 to 45 kGys; and pumping the fluid through the pipe with the pump.

23. The method according to claim 22, characterized in that the first layer is a copolymer of ethylene-vinyl acetate.

24. The method according to claim 23, characterized in that the ethylene-vinyl acetate copolymer has a melt flow index of less than about 5.0 g / 10 minutes.

25. The method. according to claim 23, characterized in that ethylene-vinyl acetate copolymer has a flow melt index of less than about 1.0 g / 10 minutes.

26. The method according to claim 23, characterized in that the ethylene-vinyl acetate copolymer has a lower melt flow rate of about 0.80 g / 10 minutes.

27. The method according to claim 23, characterized in that the second layer is an ethylene and an alpha olefin copolymer where the alpha olefin has from 3 to 8 carbons.

28. The method according to claim 27, characterized in that the second layer is an ultra-low density polyethylene.

29. The method according to claim 22, characterized in that the pipe additionally comprises a third layer.

30. The method according to claim 22, characterized in that the gel content of the ethylene-vinyl acetate copolymer is about 0-49%.

31. The method according to claim 22, characterized in that the step of exposing the pipe to the dose of radiation sterilization comprises the step of exposing the pipe to a radiation source selected from the group consisting of gamma rays, ultraviolet rays, and a beam of electron.

32. The method according to claim 22, characterized in that the pipe includes a radiation sensitive additive.

33. The method according to claim 32, characterized in that the radiation sensitive additive is selected from a compound containing at least one functional group selected from the group consisting of organic peroxides, acrylates, acids, amides, amines, silanes , urethanes, hydroxyls, epoxies, esters, pyrrolidones, acetates, carbon oxides, ketones, imidazolines, photo initiators, fluoro compounds, and dienes.

34. The method according to claim 33, characterized in that the compound containing the functional group diene is an EPDM.

35. The method according to claim 33, characterized in that the compound containing a diene functional group is a syndiotactic of 1,2-polybutadiene.

36. The method according to claim 33, characterized in that the compound containing a diene functional group is a styrene-butadiene block copolymer.

37. A medical tubing for use with a pump for administering measured quantities of a beneficial fluid over time to a patient characterized in that it comprises: a side wall of the tubing having a first layer selected from the group consisting of homopolymers of ethylene and ethylene copolymers, wherein the ethylene copolymers are ethylene copolymerized with a monomer selected from the group consisting of lower alkyl olefins having 3-10 carbons, lower alkyl esters of a carboxylic acid, lower alkyl having 3-10 carbons, and lower alkene esters of a carboxylic acid, the lower alkene has 3-10 carbons, the side wall has a melt flow index of less than about 5.0 g / 10 minutes; where the pipeline has been exposed to a radiation sterilization dose from about 15 to about 45 kGys.

38. The pipe according to claim 37, characterized in that the first layer is a copolymer of ethylene-vinyl acetate.

39. The pipe according to claim 38, characterized in that the ethylene-vinyl acetate copolymer has a melt flow index of less than about 1.0 g / 10 minutes.

40. The pipeline according to claim 38, characterized in that the ethylene-vinyl acetate copolymer has a melt flow index of less than about 0.80 g / 10 minutes.

41. The pipe according to claim 37, characterized in that the pipe additionally comprises a second layer concentrically disposed within the first layer.

42. The pipe according to claim 41, characterized in that the second layer has a modulus of elasticity that is greater than a modulus of elasticity of the first layer.

43. The pipe according to claim 42, characterized in that the second layer is an ethylene and an alpha olefin copolymer where the alpha olefin has from 3 to 8 carbons.

44. The pipe according to claim 43, characterized in that the second layer is an ultra-low density polyethylene.

45. The pipe according to claim 41, characterized in that the pipe additionally comprises a third layer.

46. A medical tubing for use with a pump for administering measured quantities of a beneficial fluid over time to a patient characterized in that it comprises: providing a tubing having a first layer selected from the group consisting of ethylene homopolymers and ethylene copolymers, wherein the copolymers of ethylene are ethylene copolymerized with a monomer selected from the group consisting of lower alkyl olefins having from 3 to 18 carbons, lower alkyl esters of a carboxylic acid, lower alkyl having from 3 to 18 carbons, and esters of lower alkene of a carboxylic acid, the lower alkene has from 3 to 18 carbons, the pipe has been exposed to a radiation sterilization dosage from about 15 kGys to about 45 kGys; and where the pipe is formed by an extrusion process by an extruder, and where the pipe is cooled in a solid state to define an initial diameter and then the pipe is stretched in a direction along a longitudinal axis of the pipe to define an oriented diameter that is smaller than the initial diameter.

47. The pipe according to claim 46, characterized in that the initial diameter is from 10% -300% greater than the oriented diameter.

48. The pipe according to claim 46, characterized in that the initial diameter is from 20% - 120% greater than the oriented diameter.

49. The pipe according to claim 46, characterized in that the initial diameter is from 30% -100% greater than the oriented diameter.

50. The pipe according to claim 46, characterized in that the first layer is a copolymer of ethylene-vinyl acetate.

51. The pipe according to claim 50, characterized in that the ethylene-vinyl acetate copolymer has a melt flow index of less than about 5.0 g / 10 minutes.

52. The pipe according to claim 50, characterized in that the ethylene-vinyl acetate copolymer has a melt flow index less than about 1.0 g / 10 minutes.

53. The pipe according to claim 50, characterized in that the ethylene-vinyl acetate copolymer has a melt flow index of less than about 0.80 g / 10 minutes.

54. The pipe according to claim 50, characterized in that it comprises a second layer concentrically disposed within the first layer, the second layer has a modulus of elasticity greater than a modulus of elasticity of the first layer.

55. The pipe according to claim 54, characterized in that the second layer is an ethylene and an alpha olefin copolymer where the alpha olefin has from 3 to 8 carbons.

56. The pipe according to claim 55, characterized in that the second layer is an ultra-low density polyethylene.

57. A method of manufacturing tubing for use for a pump by administering measured quantities of a beneficial fluid over time to a patient, the method characterized in that it comprises the steps of: providing a polymeric material selected from the group consisting of ethylene homopolymers and copolymers of ethylene, wherein the ethylene copolymers are ethylene copolymerized with a monomer selected from the group consisting of lower alkyl olefins having from 3 to 18 carbons, lower alkyl esters of a carboxylic acid, lower alkyl having from 3 to 18 carbons , and lower alkene esters of a carboxylic acid, the lower alkene has from 3 to 18 carbons, the polymeric material having a melt flow index less than about 5.0 g / 10 minutes; extruding the polymeric material in a pipe having a first layer with an extruder; and exposing the tubing to a dose of radiation sterilization from about 15 to about 45 kGys.

58. The method according to claim 57, characterized in that the additional method comprises the steps of: cooling the pipe leaving the extruder to a solid phase to define an initial diameter, and stretching the pipe in a solid phase to define a diameter oriented that is smaller than the initial diameter.

59. The method according to claim 58, characterized in that the initial diameter is from 10-300% greater than the oriented diameter.

60. The method according to claim 57, characterized in that the polymeric material is an ethylene-vinyl acetate copolymer having a vinyl acetate content of not more than 36% vinyl acetate by weight of the copolymer.

61. The method according to claim 60, characterized in that the gel content of the ethylene-vinyl acetate copolymer is from about 0-49%.

62. The method according to claim 61, characterized in that the ethylene-vinyl acetate copolymer has a melt flow index of less than about 1.0 g / 10 minutes.

63. The method according to claim 62, characterized in that the ethylene-vinyl acetate copolymer has a melt flow index of less than about 0.80 g / 10 minutes.

64. The method according to claim 62, characterized in that the step of exposing the pipe to radiation sterilization dose comprises the step of exposing the pipe to a radiation source selected from the group consisting of gamma rays, ultraviolet rays, and a beam of electron.

65. The method of conformance with --- claim 57, characterized in that the step of extruding a pipe having a first layer additionally includes the step of extruding a pipe having a second layer concentrically disposed within the first layer of the pipe.

66. "The method according to claim 5; characterized in that the second layer has a modulus of elasticity that is greater than a modulus of elasticity of the first layer.

67. The method according to claim 66, characterized in that the second layer is selected from homopolymers and copolymers of alpha olefins.

68. The method according to claim 67, characterized in that the second layer is an ultra-low density polyethylene.