JPH0157582B2 - - Google Patents

Description

[Detailed description of the invention]

[Industrial Application Field] The present invention relates to a multilayer blood bag in which the layer in direct contact with blood is made of addition-polymerized silicone rubber. [Prior Art] For most blood containers, the conventionally used glass bottles have been replaced by flexible polyvinyl chloride resin bags, which are easier to handle and can be used in closed systems. The performance required for a blood container is that the inner surface of the container should be sterile, and at the same time, there should be no risk of microorganisms entering from the outside. In order to be sterile, it is desirable to be able to withstand sterilization at temperatures above 121°C, such as in an autoclave, and on the other hand, to withstand freezing, at least -30°C, preferably the temperature of liquid nitrogen -196°C. In terms of strength, for the purpose of fractionating components such as blood cell components and plasma components, the minimum requirement is to have strength and flexibility that can withstand centrifugation. Furthermore, regarding the preservation property of blood components, it is required that there is little platelet adhesion, that there is no risk of destruction of blood cell components, that water vapor permeability is low, and that oxygen permeability is good. In recent years, blood containers have become multi-bagged, such as parent-child bags, double bags, triple bags, and quadruple bag bags.The biggest factor behind this is that they can be operated aseptically. It is desirable that the bag and tube be easily connected by heat welding, adhesive, etc. so that they can be connected aseptically. Furthermore, if possible, it is more preferable if the packaging has good transparency so that the condition of the packaged blood can be seen. Blood bags made of soft vinyl chloride, which are widely used, have excellent transparency, strength, and heat resistance, and can withstand temperatures as low as -30°C. Furthermore,
The container has excellent processability and is economically satisfactory.
However, soft vinyl chloride bags are DOP
Because it contains plasticizers, plasticity may dissolve into the blood. Furthermore, since they tend to fuse together at the autoclave temperature, special consideration is required during autoclave treatment. Regarding the preservation of blood cell components, which has become important in recent years, another problem is the high platelet adhesion as a material problem. In order to improve such bags made of vinyl chloride, for example, silicone oil is kneaded into a soft vinyl chloride resin composition as seen in Japanese Patent Application Laid-Open No. 54-45354, As stated in the publication, by subjecting the surface of a soft vinyl chloride resin molding to low-temperature plasma treatment in an atmosphere of argon, carbon monoxide, nitrogen, carbon dioxide, etc., it is possible to prevent the elution of plasticity and to prevent platelet growth. Attempts have been made to prevent adhesion. Further, in Japanese Patent Application Laid-Open No. 116466/1984, an attempt has been made to prevent platelet adhesion by providing a thin film of silicone resin on the surface of a soft vinyl chloride resin treated with low temperature plasma. In addition,
Platelet storage bags and frozen red blood cell storage bags made of polyethylene cross-linked films that do not have to worry about plasticizer elution, and frozen red blood cell storage bags made of composites based on polyimide or polytetrafluoroethylene films have been proposed. As mentioned in the previous reference, silicone rubber has good compatibility with blood and is already used in many medical applications, but although this material has excellent heat resistance, it has poor strength, especially tear resistance. Currently, it is too weak to be used as a single blood bag for practical purposes.
Also, in terms of processability, adhesion of silicone rubber is extremely difficult, so there are problems with connection of the port and tube parts that are essential to the bag, and adhesion between the bag and the port part. Furthermore, in the case of blood collection bags, sampling is performed on a part of the tube in order to check the blood type and suitability of the blood, and methods are used to heat seal the tube in order to separate the tube from the blood collection needle. However, silicone rubber does not meet this purpose because it does not have thermal adhesive properties. The problem with olefin bags is the connection between the tube and the port, which is the biggest problem with these resin bags, which have almost no adhesive. The inventors of the present invention have continued to study intensively how to compensate for the advantages and disadvantages of these thermoplastic resins and the advantages and disadvantages of silicone rubber. It has been discovered that a certain combination of vinyl chloride resin and addition-polymerized silicone rubber surprisingly provides strong adhesive strength. Similarly, nylon, polyethylene, polypropylene, cross-linked polyethylene,
It has also been discovered that ethylene-propylene copolymers, ethylene-vinyl urate copolymers, and crosslinked ethylene-vinyl acetate copolymers can be bonded to special addition-polymerizable silicone rubbers. [Object of the Invention] The present invention applies the results of previous research showing that soft vinyl chloride resins, polyolefin resins, etc. and addition-polymerized silicone rubber can be strongly bonded to each other. The aim is to solve the problems of conventional blood bags. [Structure of the Invention] That is, the present invention provides a bag having an inner layer in direct contact with blood made of an addition polymerization type silicone rubber and an outer layer made of a thermoplastic polymer, and a composition of the addition polymerization type silicone rubber. is a polysiloxane containing one vinyl group at each end, and an amount sufficient to provide 1 to 6 hydrogen atoms directly bonded to a silicon atom per vinyl group in the composition. and an organohydrogenpolysiloxane having two or more hydrogen atoms, and the thermoplastic polymer contains 0.1 to 10wt% of an organohydrogenpolysiloxane containing 40mol% or more of organohydrogensiloxane units in its components. The purpose of the present invention is to provide a silicone rubber multilayer blood bag that has excellent characteristics such as blood storage properties and platelet adhesion properties. The silicone rubber layer constituting the silicone rubber multilayer blood bag according to the present invention is an addition polymerization type silicone rubber, and the addition polymerization type silicone rubber is composed of a vinyl group-containing polysiloxane represented by the general formula (1) and a general It is a composition that can be solidified into an elastic body by addition polymerizing organohydrogenpolysiloxane represented by formula (2) and an inorganic material such as silica as a reinforcing agent using a catalyst such as platinum. [In the formula, R ₅ , R ₇ to _{R 10} : Same or different monovalent hydrocarbon groups having 6 or less carbon atoms R ₆ : Hydrogen group or same or different monovalent hydrocarbon groups n having 3 or less carbon atoms: Integer 2 or more and 100 or less l: 0 or a positive integer of 100 or less If an organohydrogenpolysiloxane having two or more hydrogen atoms in one molecule is contained in an amount sufficient to provide hydrogen atoms directly bonded to silicon atoms at a ratio of preferably 1 to 6 times, the thermoplastic property can be further improved. Increases adhesive strength with resin. Also, epoxy compounds as a component of what is generally called self-adhesive silicone rubber,
A cured layer obtained by adding a carboxylic acid anhydride, a silane or siloxane containing an acryloxyalkyl group represented by the general formula (3), or an oxirane compound containing an unsaturated hydrocarbon group, or after solidifying an addition polymerizable silicone composition. It is also possible to add a vinyl group-containing resin-like copolymer that is compatible with the components represented by general formulas (1) and (2) as a component for improving the physical properties of the material. For example, there are copolymer organopolysiloxanes of general formulas (4), (5) and (6). [In the formula, _R11 : _CH3 or H group n: a positive integer of 1 to 3] ( _CH2 =CH)( _R13 )( _R14 ) _SiO0.5 ......(4) _SiO2 ......(5 ) (R ₁₅ ) ₃ SiO _0.5 ......(6) [In the formula, R ₁₃ , R ₁₄ , R ₁₅ : Same or different monovalent hydrocarbon groups having 6 or less carbon atoms] On the other hand, the outer layer is directly coated with silicone rubber. However, the outer layer of the bag may be made of soft vinyl chloride resin, polyurethane, nylon, polyester, polyethylene, polypropylene, cross-linked polyethylene, ethylene-vinyl acetate copolymer (EVA), cross-linked EVA, ethylene-propylene copolymer, etc. 1 selected from ethylene copolymers or multicomponent copolymers such as polymers, ionomer resins, and butadiene copolymers such as polybutadiene, butadiene-styrene copolymers, butadiene-ethylene-styrene ternary copolymers, etc. Thermoplastic polymers such as seeds or blends of two or more can be used. In particular, in the case of bags containing blood preservation solutions such as ACD solutions that require autoclave sterilization, soft vinyl chloride resin, nylon, polyester, polypropylene, cross-linked polyethylene, cross-linked EVA, ethylene-
Heat resistant resins such as propylene copolymers are preferred. In addition, in these thermoplastic resin films,
Those containing 0.1 to 10 wt% of organohydrogenpolysiloxane containing 40 mol% or more of organohydrogensiloxane units provide even better adhesion to addition polymerizable silicone rubber. When using olefin resins, as stated in the inventors' earlier patent application, the adhesive strength of olefin resins is better if they contain a relatively large number of unsaturated double bonds in the molecule, such as If a substance having many unsaturated double bonds, such as polyethylene, is added in the form of a blend, the adhesive strength will be further improved. This blood bag can be manufactured by, for example, applying addition polymerized silicone rubber to one side of a soft vinyl chloride resin by a doctor blade method, a roll coater method, a spray method, a screen printing method, etc. 10 μ~ on the part to be
After coating to a thickness of 300μ, preferably 15μ to 100μ, it is coated at 40℃ to 130℃, preferably
Heat at 80°C to 110°C to form a hardened layer. The upper limit of the heating temperature is determined by the heat resistance of the resin, and in the case of cross-linked polyethylene, polypropylene, nylon, and polyester, which have higher heat resistance, the temperature can be raised further, and the higher the temperature, the faster the cure. and can be bonded. In general, silicone rubber tends to block each other when it has a smooth surface, so it is preferable to emboss the rubber to prevent blocking. In this case, the emboss can be performed using a Teflon-treated heating drum. Regarding the bag making process, two sheets of addition polymerization type silicone rubber are stacked with the cured layer side on the inside, and when the entire surface is coated, an addition polymerization type silicone rubber composition is further coated on the bag body sealing part and bonded by heating. Can be done. In this case, the adhesion can be further improved by heating under pressure.
The same applies to the adhesion of the port portion. At this time, the thickness of the silicone rubber to be coated is preferably 10 μm or more and 1 mm, and about 100 to 300 μm considering processability, although the thicker the adhesive strength is. In the case where the coating is partially coated, high-frequency adhesion or welding may be used as commonly practiced, and the addition-polymerizable silicone rubber composition of the present invention may be used as an adhesive as described above. good. [Effects of the Invention] The silicone rubber multilayer blood bag thus obtained has extremely excellent performance as a bag for storing platelets, and also as a bag for storing red blood cells compared to conventional bags for whole blood. It can be used as an excellent item. The effects of the present invention will be explained below with reference to Examples. Example Bag 1 100 parts by weight of vinyl chloride resin, 1.2 parts by weight of calcium-zinc composite stabilizer, 42 parts by weight of DOP, 8 parts by weight of epoxidized soybean oil, and 7.5 parts by weight of organohydrogenpolysiloxane containing 45 mol% of organohydrogensiloxane units. 100 parts by weight of dimethylpolysiloxane with a viscosity of 18,000 cp and having vinyl groups at both ends, and 10 mol of trimethylsiloxane units in the methylhydrogen polysiloxane component were sheeted to a thickness of 0.3 m/m using a calender.
%, 40 mol% dimethylsiloxane units, 50 mol% methylhydrogen siloxane units, 8 parts by weight of polysiloxane, 20 parts by weight of silica, and 0.3 parts of isopropyl alcohol solution of platinum chloride (platinum content: 1%).
Add parts by weight, mix, dilute with n-hexane, and cure the solution using a doctor blade method until the thickness is approx.
After coating to a thickness of 100 μm and removing n-hexane, it was covered with Teflon-coated glass cloth paper and placed in a constant temperature bath at 110° C. for 2 hours to crosslink and solidify. After that, the silicone rubber surface was coated with an undiluted addition-polymerized silicone rubber composition to a thickness of about 100 μm in a shape that would form the circumference of the bag body, and the aforementioned soft vinyl chloride extrusion tube (OD 6 mm x ID 4 mm) was used as a port. Insert and press at 110℃
The bag was cured by heating for 2 hours. Bag 2 A polyvinyl chloride sheet obtained in the same manner as Bag 1 was coated with an addition-polymerizable silicone rubber composition to a thickness of about 50 μm only on the inner surface of the bag, and cured by heating in the same manner. . Thereafter, the periphery was high-frequency welded using an ordinary high-frequency bag making machine to obtain a bag body. Bag body 3: 100 parts by weight of polypropylene and 20 parts by weight of polyethylene
45 mol of organohydrogen siloxane units per part by weight
A resin blended with 6.0 parts by weight of organohydrogenpolysiloxane containing 100% was extruded to a thickness of 100μ to obtain a film. To the film,
The addition polymerization type silicone composition used in bag body 1
Coated to a thickness of 100μ, covered with Teflon-coated glass cloth paper after vacuum degassing, and heated at 115℃ for 1 hour.
A silicone rubber-polyolefin composite film was obtained by time pressing. Similar to bag 1, the surrounding area was coated with an addition-polymerizable silicone rubber composition, a vinyl chloride resin tube was sandwiched between two sheets as a port, and the mixture was heated and cured at 110°C for 1.5 hours while being embossed. A bag body was obtained. Bag 4 As a comparative example, a soft vinyl chloride resin sheet shown in Bag 1 was used and subjected to high frequency processing to obtain Bag 4. The bag thus obtained was sterilized by autoclaving at 120°C for 30 minutes. 50 ml of ACD dog whole blood was dispensed into these bags, stored at 4°C, and the number of floating platelets was measured after 1, 4, 8, 24, and 48 hours, and the platelet residual rate was determined. In addition, to check the storage stability of red blood cells, hemolysis was determined by counting the amount of red blood cells after storage for 24 days.

【table】

[Table] As is clear from the results in Tables 1 and 2, the bag (blood bag) according to the present invention has significantly improved preservation of both platelets and red blood cells. The physical properties of the bag according to the present invention are as follows.

【table】

Claims (1)

[Scope of Claims] 1. A bag in which the inner layer in direct contact with blood is an addition-polymerizing silicone rubber, and the outer layer is a thermoplastic polymer, and the composition of the addition-polymerizing silicone rubber is at both ends. polysiloxane containing one vinyl group each, and one vinyl group in the composition.
The thermoplastic polymer mainly contains an organohydrogenpolysiloxane having two or more hydrogen atoms per molecule in an amount sufficient to provide 1 to 6 hydrogen atoms directly bonded to silicon atoms, and the thermoplastic polymer Contains organohydrogensiloxane units in its components.
Organohydrogen polysiloxane containing 40 mol% or more
A blood bag characterized by containing 0.1 to 10wt%. 2 The thickness of the addition polymerized silicone rubber layer is 10~
The blood bag according to claim 1, characterized in that the blood bag has a diameter of 300μ. 3. The blood bag according to claim 1, characterized in that the surface of the addition-polymerized silicone rubber on the side that comes into contact with blood is an embossed surface. 4 The thermoplastic polymer layer on the outside of the bag is made of soft vinyl chloride resin, polyurethane, nylon, polyester, polyethylene, polypropylene, cross-linked polyethylene, ethylene-propylene copolymer, ethylene-vinyl acetate copolymer, cross-linked ethylene- Selected from ethylene copolymers or multicomponent copolymers such as vinyl acetate copolymers and ionomer resins, and butadiene copolymers such as polybutadiene, butadiene-styrene copolymers, butadiene-ethylene-styrene ternary copolymers, etc. 2. A blood bag according to claim 1, characterized in that the blood bag is comprised of a film made of one or more blended products.