JPH04180761A - Fluid therapy bag - Google Patents

Abstract

PURPOSE:To simply execute the sterilization processing by making the fluid therapy bag by a flexible film which consists of copolymer polyester whose Tcg is <=60 deg.C, and whose tensile Young's modulus is 0.1--50kg/mm<2>. CONSTITUTION:The fluid therapy bag is made of a flexible film which consists of copolymer polyester whose Tcg is <=60 deg.C, and whose tensile Young's modulus is 0.1-50kg/mm<2>. As for the copolymer polyester, it is desirable that at least two kinds of diole component residual groups selected from HO-(CH2)2n-OH(n: 1-10) are contained as an alcohol component, and 40-99mol % aromatic dicarboxylic acid residual groups, and 60-1mol % long chain aliphatic dicarboxylic acid residual groups are contained against the whole acid component. The most general method for forming the fluid therapy bag by using the film is a method executed by heat seal, but even when the flexible film is subjected to heat seal, it is desirable that internal haze of its seal part is suppressed low, and as for the internal haze of the seal part, it is desirable that it is less than 4%.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention relates to an infusion bag using a flexible copolyester film.

[Conventional technology]

BACKGROUND ART Infusion bags, which are liquid bags used during drip drips or blood transfusions, have conventionally been made by forming a soft vinyl chloride sheet into a bag shape by heat sealing or the like. Also, recently, those using polyolefin-based soft materials have been used.

[Invention or problem to be solved]

However, the infusion bags made of soft vinyl chloride that have been used so far have the following problems.

First, vinyl chloride contains a plasticizer, so during long-term use, the plasticizer may bleed out and contaminate the infusion solution stored in the infusion bag, creating a hygiene problem. There is a risk of

Furthermore, monomers precipitated from soft vinyl chloride may be problematic in their toxicity, which may also pose a sanitary problem.

Additionally, vinyl chloride usually does not have very high chemical resistance, which limits the drugs that can be used in the infusion bag. This makes widespread use of the infusion bag medically difficult.

Furthermore, vinyl chloride is decomposed by γ-ray irradiation, so
Only gamma ray sterilization is possible. Normally, sterilization is carried out in an autoclave at about 20'C, but sterilization takes too long, resulting in poor productivity of infusion bags, and the sterilization equipment becomes bulky.

The present invention focuses on the problems of infusion bags made of soft vinyl chloride, and is made of a polymer that does not contain plasticizers and has excellent chemical resistance, which eliminates hygiene problems and allows for a wide range of uses. The purpose of the present invention is to provide an infusion bag that can be sterilized in a very simple manner.

[Means to solve the problem]

The infusion bag of the present invention that meets this purpose is △Tcg or 60
It consists of a flexible film made of copolymerized polyester with a temperature below ℃ and a tensile Young's modulus of 0.1 to 50 kg/mm2.

The copolymerized polyester constituting the flexible polyester film of the present invention has a ΔTcg defined as the difference between the cold crystallization temperature (TcC) and the glass transition temperature (Tg) (Tcc - Tg) of 60°C or less. The temperature is preferably 50°C or lower. If ΔTcg is too large, problems such as an increase in tensile Young's modulus over time and swelling or whitening of the film during heat sealing to form an infusion bag will occur.

Specific examples of the composition of the copolyester include the following.

That is, as the soft segment, polyoxyalkylene glycols such as polyethylene glycol and polytetramethylene glycol, polyε-caprolactone, acelaic acid, sebannic acid, dodecanedioic acid,
Is it preferable to use an aliphatic polyester consisting of a HOOC-[CH2], -000H aliphatic dicarboxylic acid such as dimer acid and an aliphatic and/or alicyclic diol? In particular, as a soft segment, a long-chain aliphatic It is preferable that it contains dicarboxylic acid, since it has good heat resistance, weather resistance, and transparency.

In the present invention, the long-chain aliphatic dicarboxylic acid refers to a dicarboxylic acid having an alkylene group having 8 to 60 carbon atoms, such as sebacic acid, eicoic acid, dodecanedioic acid, and dimer acid, and particularly having an alkylene group having 10 to 50 carbon atoms. This range is preferable because it provides good flexibility.

In particular, in the present invention, among long-chain aliphatic dicarboxylic acids, it is preferable to use a long-chain branched aliphatic dicarboxylic acid having a branched structure, and among these, dimer acid is preferably used because it has good heat resistance and transparency. It is preferable to do so.

Here, dimer acid is a mixture of a chain branched structure and a cyclic branched = 4- structure obtained by a dimerization reaction of unsaturated aliphatic carboxylic acid methyl ester such as methyl oleate, and usually has an unsaturated bond. in the molecule or hydrogenated, with a bromine number of 0.05 to 10 g/100
g, preferably 0.1 to 5 g/100 g, since it has excellent heat resistance and flexibility.

As for the hard segment of the copolyester mentioned above,
In order to improve heat resistance and solvent resistance, it is preferable that the melting point is 200°C or higher, the glass transition temperature is 90°C or lower, and ΔTcg is 80°C or lower when the polymer is formed alone.
Specifically, ethylene terephthalate, butylene terephthalate, cyclohexane dimethylene terephthalate,
Preferably, it is composed of at least one selected from aromatic and/or alicyclic ester units such as cyclohexane dimethylene cyclohexane dicarboxylate and butylene-naphthalene dicarboxylate.

Among these, those having terephthalic acid residues are particularly preferred because they have good weather resistance.

Here, the intrinsic viscosity of the copolymerized polyester preferably used is 05 to 2.0 dl/g, preferably,
It is 0.7-1.8 dl/g. By setting the intrinsic viscosity within such a range, both film formability and mechanical properties of the polyester film are improved.

Further, the melting point (Tm) of the copolyester is preferably in the range of 130 to 250°C, more preferably in the range of 140 to 230°C. Further, the glass transition temperature (Tg) is preferably 10°C or lower, more preferably 0°C or lower.

be.

The copolymerized polyester in the present invention contains H○-(CH2) as an alcohol component.2. OH (n1-10)
Contains at least two types of diol component residues selected from
It is preferable to contain 99 mol % and 60 to 1 mol % of long chain aliphatic dicarboxylic acid residues.

Here, the alcohol component HO(CH2)2. -OH(n
: I to 10) are aliphatic diol components such as ethylene glycol, 1.4 butanediol, 1,6 hexanediol, 1.8-octanediol, etc., and preferably n is in the range of 1 to 4. This is preferable in order to improve the mechanical properties and heat resistance of the flexible film.

It is preferable that the copolyester in the present invention contains at least two of the alcohol components listed in 1. Here, in the present invention, each alcohol component is 5 mol%
It is defined as being present when it contains more than

If an attempt is made to configure the alcohol component into a one-component system, problems such as increased self-adhesiveness and deterioration of transparency arise. Especially diol compositions.

1,4-butanediol is preferable because mechanical properties and transparency are good.・Also, is it permissible to contain a small amount of branched glycol residues such as propylene glycol or neopentyl glycol?
It is preferable to keep it below mol%, preferably below 5 mol%. Similarly, alcohol components containing ether groups such as diethylene glycol are also allowed to be included as by-product components. Usually 0. The O content ranges from about 1 to 4 mol%.

The copolymerized polyester of the present invention preferably contains 40 to 99 mol% of aromatic dicarboxylic acid residues and 60 to 1 mol% of long chain aliphatic dicarboxylic acid residues. If the content of aromatic dicarboxylic acid residues is less than 40 mol %, heat resistance and weather resistance will be poor. On the other hand, if the aromatic dicarboxylic acid content exceeds 99 mol%, the bag loses flexibility and becomes unsuitable for use as an infusion bag.

Here, aromatic dicarboxylic acids include terephthalic acid, isophthalic acid, 2,6-naphthalene dicarboxylic acid, 5-sodium sulfoisophthalic acid, diphenic acid, etc. Among these, terephthalic acid has good weather resistance and flexibility. This is preferable. Further, the long-chain aliphatic dicarboxylic acid is as described above.

The flexible film made of the copolyester of the present invention must have a tensile Young's modulus in the range of 0.1 to 50 kg/mm2, preferably 1 to 30 kg/mm2.
/ mm2 range. If the tensile Young's modulus is too small or too large, problems will occur in winding properties during flexible film formation, processing suitability during infusion bag processing, shape retention as an infusion bag, etc.

In the infusion bag of the present invention, the higher the transparency of the flexible polyester film constituting the infusion bag, the better. Therefore, the lower the haze of the flexible film, the better. In particular, as a very simple method to sterilize infusion bags, the haze of 100 μm equivalent after immersion in boiling water is 4.
% or less is preferable.

From the same point of view, the lower the internal haze, the better.

The most common method of forming an infusion bag using a film is by heat sealing, or even when the above flexible film is heat sealed, it is desirable that the internal haze of the sealed part is low (suppressed). The internal haze of the part is preferably less than 4%.

Further, as a characteristic of the infusion bag, it is necessary that extracts and precipitates from the flexible film constituting the infusion bag do not mix with the infusion contained in the infusion bag. From this point of view, it is desirable that the flexible film constituting the infusion bag has a small loss of weight when extracted with a solvent, such as acetone, and it is preferable that the weight loss when extracted with acetone is 10% or less.

From the same point of view, the Japanese Pharmacopoeia 10th Revised General Test Method 42
As stipulated in the "Test Method for Plastic Containers for Infusions," when water is placed in an infusion bag and the water is heated to a predetermined temperature and eluted for a predetermined period of time, the amount of impurities must be below the specified amount. It is also necessary that the foaming at that time disappear within a specified time. The details will be described in the evaluation method and examples section below.

The flexible polyester film of the present invention is preferably a substantially non-oriented film in order to improve long-term dimensional stability. Here, "substantially non-oriented" means that the orientation of the molecular chains is sufficiently small and the anisotropy of mechanical properties and anisotropy of engineering properties are at a sufficiently negligible level, for example, in the longitudinal direction. Ratio of breaking strength in width direction is 0.6
~1°4 range, or the absolute value of the difference in refractive index (Nx, Ny, Nz) in the longitudinal direction, width direction, and thickness direction 1
Ni-Njl (i, j=x, y, z, i≠j) or 0
．． It is preferably less than 1, preferably less than 0.05. If the material has substantial orientation, it may deform if left for a long period of time, causing practical problems.

Next, a method for manufacturing an infusion bag according to the present invention will be described, but of course the method is not limited thereto.

A. Production of copolymerized polyester Aromatic and/or alicyclic dicarboxylic acids constituting a predetermined hard segment, or dimethyl esters thereof, and a soft segment and a corresponding alcohol component are added and copolymerized by a well-known polyester polymerization method. Obtain polyester.

B. Manufacture of flexible polyester film After drying the copolymerized polyester thus obtained, it is melt extruded from an extruder, extruded from a T-shaped nozzle or circular nozzle in the form of a sheet or cylinder, and then extruded using a cooling roll or a circular nozzle. , introduced into a coolant such as water, and solidified (the sheet-like or cylindrical product thus obtained is hereinafter referred to as a cast film.

Usually, the extrusion temperature is in the range of melting point +10 to +80°C, and the cooling temperature is preferably in the range of 5 to 90°C, preferably 15 to 70°C.

Next, the cast film is heat treated, and the heat treatment temperature ranges from Tcc to the melting point of the copolyester (T
m), preferably in the temperature range Tcc-Tm -10°C. The treatment time is not particularly limited, but it is usually 1 second to 30 minutes, and a particularly preferred method is to perform the heat treatment in hot water or steam using a heating roll controlled at a predetermined temperature, so that the treatment is uniform and effective. This is preferable because it is accurate.

After the heat treatment, the material is introduced into a drying roll or a drying oven as required, cooled to room temperature with a cooling roll, and subjected to surface treatment, coating, etc. as required, and then wound up.

C1 Formation of an infusion bag The flexible film obtained as described above is cut into a predetermined shape, two sheets are stacked together and a predetermined portion is heat-sealed to form an infusion bag into a predetermined bag shape. γ to the obtained infusion bag
Perform line sterilization. In actual use, it is further subjected to boiling water immersion treatment.

[Method for Measuring Characteristics and Evaluating Effects] Next, methods for evaluating the characteristics and effects of the infusion bag of the present invention and the flexible film constituting it will be explained.

(1) Haze (Hloo) J Is- in terms of 100 μm
-6714, and calculated using the following formula.

Hloo (%) -HX 100/d However, H is the actual value of haze (%), and d is the film thickness (μm) of the haze measurement part.

Moreover, internal haze is similarly measured by immersing it in a quartz cell containing tetralin.

(2) For mechanical properties tensile Young's modulus, ASTM D-882-
81 (Method A).

(3) Bromine number According to ASTM-D-1159. Unit is g/100g
It is expressed as

(4) Intrinsic viscosity (TV) Measured at 25°C using 0-chlorophenol as a solvent. Units are di/g 0 (5) Melting point (Tm), glass transition temperature (Tg), cold crystallization temperature (Tcc), ΔTcg Determined using a differential scanning calorimeter DSC2 (manufactured by PerkinElmer).

The melt was held at 280° C. for 5 minutes under a nitrogen stream, and then cooled using liquid nitrogen.

When the temperature of the sample thus obtained is raised at a heating rate of 10° C./min, the change in specific heat due to the transition from the glass state to the rubber state is read and this temperature is defined as the glass transition temperature (Tg). Further, the exothermic peak temperature associated with crystallization was defined as the cold crystallization temperature (Tcc), and the endothermic peak temperature based on crystal melting was defined as the melting point (Tm).

Further, ΔTcg is defined by the following formula.

ΔTcg-Tcc-Tg (6) Acetone Extraction Weight Loss The other layers were removed from the sample to leave only the copolyester sheet (film), and after vacuum drying at 100° C. for 12 hours, the weight W+ (g) was immediately measured. Subsequently, the sample is extracted with acetone using a Soxhlet extractor for 8 hours. The extracted sample was then heated at 100°C for 1
After vacuum drying for 2 hours, the weight W2 is measured and calculated using the following formula.

Acetone extraction loss (%) = (1-Wl/W2)xlo.

(7) Eluate test After washing a sheet (film) with a surface area of 120Oc&, it was eluted with 200mj' of water at 121℃ for 11 hours, and the amount of potassium permanganate reducing substance, amount of chloride, amount of sulfate, and pH were shaken for 13 minutes. Foaming was evaluated. The test was conducted in accordance with the Japanese Pharmacopoeia O Revised General Test Method 42 [Test Method J for Plastic Containers for Infusions.

(8) Human CP adjusted to a hematocrit value of approximately 70% in a hemolysis test bag
Dispense approximately 20 D pressurized red blood cell fluid (hereinafter referred to as CR, C),
It was stored stationary at 4°C for 4 weeks. Thereafter, the plasma hemoglobin concentration was measured using the TMB method (Clinical Chemistry, VOW).
23,749-(1977)).

(9) Heat sealing property Heat sealing was performed using Fuji Impulse Sealer T130 type. Whitening of the heat-sealed part is measured by internal haze using tetralin, and those with an internal haze of less than 1% are marked as ○ and 1.
If the percentage is less than 4%, it is marked △, and if it is 4% or more, it is marked ×.

〔Example〕

Next, examples of the present invention will be described.

Example 1 Dimethyl dimer acid (Unichemer 16
~ Societies, bromine number 1g/loOg) 10 mol%, adipic acid 5 mol% and terephthalic acid 85 mol%, alcohol components: ethylene glycol 55 mol% and 1,4
- Intrinsic viscosity (TV) using 45 mol% butanediol
0.85 copolymerized polyester was polymerized.

The obtained polymer was vacuum dried at 120°C by a conventional method, melted at 220°C with a 90mmφ extruder, extruded into a sheet from a T-die, and electrostatically heated on a cooling roll at 20°C with water condensed. The impression was cast. The obtained film was further heat-treated at 80° C. for 10 seconds to obtain a transparent film with a thickness of 200 μm.

Furthermore, a mini blood bag with a capacity of 20 m (!) was prepared by stacking two of the obtained films and heat-sealing a predetermined portion, and irradiated with 3 M rad of γ-rays.

Regarding the flexible polyester film for making this infusion bag and the produced infusion bag, each property shown in Table 1 was measured and evaluated. As a result, boiling water immersion (2
The film haze after 0 minutes) and the internal haze of the heat-sealed part were sufficiently low, and the acetone extraction loss was also sufficiently low. In addition, there was no change in appearance even after sterilization by γ-ray irradiation, and in the eluate test, each eluate was below the specified amount, and the △pH was sufficiently small.
Foaming also disappeared within 3 minutes. Furthermore, sufficiently low plasma hemoglobin concentrations were obtained in the hemolysis test.

Example 2 As acid components, 20 mol% dimethyl dimerate and 80 mol% terephthalic acid; as alcohol components, 37 mol% ethylene glycol and l.

Using 63 mol% of 4-butanediol, the intrinsic viscosity (IV
)0.80 copolymerized polyester was polymerized.

A flexible film was obtained in the same manner as in Example 1, a mini blood bag was prepared, and γ-rays of 3 M r a cl were irradiated.

As a result, as shown in Table 1, good results such as a difference between Example 1 and the road were obtained.

Comparative Example 1 Dioctyl phthalate (D) was added to 100 parts by weight of polyvinyl chloride having an average degree of polymerization of about 1300.

P: manufactured by Kyowa Hakko Kogyo Co., Ltd.) 50 parts by weight, and in addition, as stabilizers, 0.1 parts by weight of calcium stearate powder, 02 parts by weight of zinc stearate powder, and parts by weight of epoxidized soybean IO were added. The mixture was kneaded with a roll at a temperature of 160° C., and then a press sheet with a thickness of 400 μm was formed.

Furthermore, a 20 ml mini-blood bag was prepared by overlapping two of the obtained sheets and heat-sealing a predetermined portion, and irradiated with 3 Mrad of γ-rays.

As a result, as shown in Table 1, the film haze after immersion in boiling water was very high at 38%, and the transparency was poor. In addition, the weight loss after acetone extraction was large, and the color turned brown after γ-ray irradiation. Also in the eluate test, the amount of potassium permanganate reducing substance was large, which greatly limits its use as an infusion bag. Furthermore, in the hemolysis test,
Plasma hemoglobin concentration was high.

Comparative Example 2 20 mol% of dimethyl dimerate and 80 mol% of terephthalic acid were used as the acid components, and 10 mol% of ethylene glycol and 90 mol% of 1°4-butanediol were used as the alcohol components, and the intrinsic viscosity (NV) was 0.75. A copolymerized polyester was polymerized.

A flexible film was obtained in the same manner as in Example 1, a mini blood bag was prepared, and 3 Mr ad γ-rays were irradiated.

As a result, as shown in Table 1, the haze was high, the transparency of the film decreased, and the flexibility deteriorated. In addition, the heat-sealed part of the mini blood bag turned white, and it tore at the border of the seal part when liquid was impacted.

〔Effect of the invention〕

As detailed above, when using the infusion bag of the present invention, the infusion bag can be constructed from a flexible polyester film that is excellent in both flexibility and transparency, and unlike the conventional infusion bag made of soft vinyl chloride. Since the polymer does not contain plasticizer, there is no problem of bleed-out.
The eluate is also sufficiently suppressed to below the specified value, and gamma ray sterilization can be applied without any problem. Further, even after immersion in boiling water and heat sealing, the haze can be kept sufficiently low, and extremely high transparency can be maintained as an infusion bag. Therefore, by using the infusion bag of the present invention in place of the conventional vinyl chloride infusion bag, it is possible to improve the mechanical properties and optical properties of the infusion bag, eliminate hygiene problems, and improve medical use. The range of possibilities can be greatly expanded.

Claims (5)

[Claims] (1) An infusion bag characterized by being made of a copolymerized polyester having a ΔTcg of 60° C. or less and a flexible film having a tensile Young's modulus of 0.1 to 50 kg/mm^2. (2) The copolymerized polyester has HO-(CH_2)_2_n-OH (n: 1 to 10) as an alcohol component.
Contains at least two types of diol component residues selected from
The infusion bag according to claim 1, containing 99 mol% and 60 to 1 mol% of long-chain aliphatic dicarboxylic acid residues. (3) The haze of the flexible film after immersion in boiling water is 4.
% or less, and the claim that the acetone extraction loss is 10% or less (
The infusion bag described in 1) or (2). (4) The infusion bag according to claim (2) or (3), wherein the long-chain aliphatic dicarboxylic acid is a dimer acid. (5) The infusion bag according to any one of claims (1) to (4), wherein the sealed portion has an internal haze of less than 4% when the flexible film is heat-sealed.