JP2013070947A - Medical container - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a medical container suppressing the water permeation of a filled liquid medicine, and suppressing the adsorption of a solute contained in the liquid medicine.SOLUTION: This medical container is made of a resin composition layer of a single layer containing polyethylene terephthalate (A) wherein limiting viscosity is 0.5-0.9 dL/g, and a propylene-based resin (B) wherein a melt flow rate (MFR) is 2-60 g/10 minutes. Preferably, the weight compounding ratio of the component (A) to the compound (B) satisfies (A)/(B)=3/7 to 7/3, and more preferably, (A)/(B)=5/5 to 7/3.

Description

  The present invention relates to a medical container comprising a single resin composition layer containing polyethylene terephthalate and a propylene resin.

The composition of a medical solution filled in a medical container may change when stored for a long period of time. One of the causes is a medical container material. As a material for medical containers filled with chemicals, especially medical containers used for eye drops, nasal drops and ear drops, mainly polyethylene terephthalate (hereinafter sometimes referred to as PET), polyethylene (hereinafter referred to as PE) And a polymer such as a propylene resin (hereinafter sometimes referred to as PP).
For example, when a PET container is used, it is known that since PET has a high water permeability, the concentration of a compound dissolved in a chemical solution tends to increase. In addition, when a container made of an olefin material such as PP is used, it is known that the concentration of the fat-soluble compound dissolved in the chemical solution tends to decrease because the solute in the chemical solution is adsorbed on the inner surface of the container. Yes.

In relation to the adsorptivity of the fat-soluble compound to the inner surface of the container, for example, in Reference 1, in a container filled with an ophthalmic solution containing L-menthol as a cooling agent, L-menthol is present on the inner surface of the container. Since it is easily adsorbed, the adsorption of L-menthol to the container is suppressed by simultaneously blending at least one component selected from polyhydric alcohols, surfactants and cyclodextrins.
Reference 1 describes the polyhydric alcohol or the like as an adsorption inhibitor in ophthalmic solutions. On the other hand, from the viewpoint of the resin material of the container, there is a demand for a method that can solve all of the above problems. Yes.

JP 2007-119422 A

  The present invention has been made in view of the above circumstances, and provides a medical container capable of suppressing moisture permeation of a filled chemical solution and suppressing adsorption of a solute contained in the chemical solution. Let it be an issue.

  By using a medical container comprising a single-layer resin composition layer containing polyethylene terephthalate having a specific range of intrinsic viscosity and a propylene-based resin having a specific range of melt flow rate, the above-mentioned problems can be solved. The inventors have found that this can be solved, and have completed the present invention.

That is, the gist of the present invention is as follows.
[1] Single layer resin containing polyethylene terephthalate (A) having an intrinsic viscosity of 0.5 to 0.9 dl / g and a propylene resin (B) having a melt flow rate (MFR) of 2 to 60 g / 10 min. A medical container comprising a composition layer.
[2] The container according to the above [1], wherein the weight blending ratio of the component (A) and the component (B) is (A) / (B) = 3/7 to 7/3.
[3] The container according to [1], wherein the weight ratio of the component (A) to the component (B) is (A) / (B) = 5/5 to 7/3.
[4] Single-layer resin comprising polyethylene terephthalate (A) having an intrinsic viscosity of 0.5 to 0.9 dl / g and a propylene resin (B) having a melt flow rate (MFR) of 2 to 60 g / 10 min. A medical container comprising a composition layer.
[5] The medical container according to any one of [1] to [4], wherein the medical container is an eye drop container, a nasal drop container, or an ear drop container.
[6] Single layer resin containing polyethylene terephthalate (A) having an intrinsic viscosity of 0.5 to 0.9 dl / g and a propylene resin (B) having a melt flow rate (MFR) of 2 to 60 g / 10 min. By using a medical container composed of a composition layer, water penetration of the chemical liquid filled in the container to the outside of the container is suppressed, and adsorption of solutes contained in the chemical liquid to the container is suppressed. Method.
[7] Polyethylene terephthalate (A) having an intrinsic viscosity of 0.5 to 0.9 dl / g and propylene resin (B) having a melt flow rate (MFR) of 2 to 60 g / 10 min are heated and melted, respectively. Melting process,
A kneading step of kneading the component (A) and the component (B) obtained in the melting step;
A pelletizing step of cooling and pelletizing the resin composition containing the component (A) and the component (B) obtained in the kneading step,
A molding step for injection molding by melting the pellet of the resin composition obtained in the pelletizing step,
The manufacturing method of the medical container in any one of said [1]-[5] containing.

  According to the medical container of the present invention, moisture permeation of the chemical liquid filled in the container to the outside of the container can be suppressed, and adsorption of the solute contained in the chemical liquid to the container can be suppressed.

  As described above, the medical container of the present invention has polyethylene terephthalate (A) (hereinafter may be abbreviated as component (A)) and propylene resin (B) (hereinafter may be abbreviated as component (B)). It is comprised from the single-layered resin composition layer containing this.

  As the polyethylene terephthalate (A) used as a raw material constituting the single-layer resin composition layer of the medical container according to the present invention, any one can be used as long as it can be normally used as a medical container. In particular, it is preferable to use a material having an intrinsic viscosity in the range of 0.5 to 0.9 dl / g from the viewpoint of excellent molding processability in the process of injection molding. The above-mentioned intrinsic viscosity in the present invention means a value measured under a temperature condition of 20 ° C. in a mixed solvent of phenol / tetrachloroethane (weight ratio 1: 1). More specifically, for example, 200 mg of component (A) is dissolved in 20 ml of a mixed solvent of phenol / tetrachloroethane (1: 1 by weight) at 105 ° C. with stirring for 20 minutes. The solution viscosity is measured with a Ubbelohde viscometer in a constant temperature water bath at 20 ° C. to obtain the intrinsic viscosity of the component (A).

  A commercially available product can be used as the polyethylene terephthalate (A), and for example, unitika polyester resins MA-1340P and MA-1344P (both manufactured by Unitika Ltd.) can be suitably used.

  The propylene-based resin (B) used as a raw material constituting the single-layer resin composition layer of the medical container according to the present invention is a propylene homopolymer, a copolymer of propylene and an α-olefin, or a mixture thereof. There may be. Examples of the α-olefin in the propylene / α-olefin copolymer include α-olefins having 2 to 20 carbon atoms excluding propylene, and examples thereof include ethylene, butene-1, hexene-1, and octene-1. Two or more α-olefins copolymerized with propylene may be used. Of these, ethylene and butene-1 are preferred. More preferably, ethylene is suitable. These propylene resins (B) may be used as a mixture of two or more.

  The propylene-based resin used in the present invention preferably has a melt flow rate (MFR) in the range of 2 to 60 g / 10 min from the viewpoint of excellent molding processability in the injection molding process. In the present invention, MFR is a value measured according to JISK7210 (test conditions: 230 ° C., 2.16 kg load).

  A commercially available product can be used as the propylene resin (B), and for example, Novatec PP series manufactured by Nippon Polypro Co., Ltd. can be suitably used.

  The medical container of the present invention comprises a single resin composition layer containing the component (A) and the component (B). The resin composition layer is a polymer blend containing the component (A) and the component (B). The weight ratio of the component (A) and the component (B) is usually used in the range of (A) / (B) = 1/9 to 9/1. However, the moisture of the chemical solution filled in the container to the outside of the container is used. (A) / (B) = 3/7 to 7/3 is preferable in that permeation can be suppressed and adsorption of solutes contained in the chemical solution to the container can be suppressed. It is more preferable to set (A) / (B) = 5/5 to 7/3 because moisture permeation can be sufficiently suppressed even when the blending ratio is low.

  The resin composition layer may be composed only of the component (A) and the component (B). However, as long as the effects of the present invention described above are not impaired, the resin composition layer is further compatible with a block copolymer of styrene-butylene ethylene. An agent may be added.

As a manufacturing method of the medical container of the present invention, the melting step of heating and melting components (A) and (B), and optional components such as a compatibilizer as necessary, in the melting step Kneading step of kneading each component obtained, pelletizing step of cooling and pelletizing the resin composition containing each component obtained in the kneading step, of the resin composition obtained in the pelletizing step Melting the pellet and performing injection molding.
In the present invention, as described above, the resin composition that is a melt-kneaded product of the above-described components may be produced by kneading the components separately and then kneading or kneading the components together. May be manufactured. When the above components are melted or kneaded separately or together, a single screw extruder, a twin screw extruder, a Banbury mixer, a plastic bender, a roll or the like can be used.

  In addition, since the component (A) has a high moisture content, it is desirable to heat and dry it for a sufficient time before melting. In the pelletization step, it is desirable to control the temperature and the stirring speed during kneading so that the resin composition does not become a ball shape.

  The medical container of the present invention is suitable as an eye drop container, nasal drop container or ear drop container, and can be used in combination with members such as a nozzle and a cap. The materials such as nozzles and caps are not particularly limited, but for example, PET, PP, PE, etc. are used. As a nozzle material suitable for the container, it is desirable to use PE from the viewpoint of fitting. Moreover, it is desirable to use PP as a cap material suitable for this container from the viewpoint of airtightness.

  The type of the chemical solution filled in the medical container of the present invention is not particularly limited, but when the solute contained in the chemical solution is a lipophilic drug, an aromatic compound such as a terpenoid compound or a surfactant, the present invention The effect can be remarkably obtained.

  Drugs with high fat solubility are those within the scope of the term “not easily soluble in water to hardly soluble in water” as described in the Japanese Pharmacopoeia, including non-steroidal anti-inflammatory analgesics, steroids, etc. , Immunosuppressants and antibiotics, vitamins.

  Terpenoid compounds include menthol, camphor, borneol, geraniol, cineol and linalool. Particularly in the case of menthol, the effect of the present invention is remarkable.

  Examples of the surfactant include nonionic surfactants, cationic surfactants, anionic surfactants and amphoteric surfactants. In particular, quaternary ammonium type cationic surfactants ( In particular, in the case of benzalkonium chloride), the effect of the present invention is remarkable.

  The medical container of the present invention can suppress the water permeation of the chemical liquid filled in the container to the outside of the container, and can suppress the adsorption of the solute contained in the chemical liquid to the container. The moisture permeability is determined using as an index the amount of moisture decrease due to moisture permeation of the chemical solution filled in the medical container. As the amount of moisture reduction, when stored at 40 ° C. and a relative humidity of 25% or less for 14 days, it is usually desirable to be able to suppress the initial weight to 1% or less, preferably 0.7% or less. In addition, as another standard of water loss, for example, in a water loss test based on the stability test guideline of the Japan-US EU Pharmaceutical Regulation Harmonization International Conference, water loss after storage for 3 months at 40 ° C and relative humidity of 25% or less is initial. It is desirable to be 5% or less of the weight. The adsorptivity of a solute is determined by using as an index the residual rate of the solute when the amount of adsorption of the solute in the chemical solution filled in the medical container reaches a certain level. In particular, when the solute is an additive of a chemical solution, it is desirable that the residual rate of the solute is 50% or more, preferably 60% or more with respect to the initial solute weight in consideration of the effect of the solute.

  As described above, in order to suppress the moisture permeation of the chemical solution filled in the medical container to the outside of the container and to suppress the adsorption of the solute contained in the chemical solution to the container, it has a specific range of intrinsic viscosity. It is important to use a medical container composed of a single resin composition layer containing polyethylene terephthalate (A) and a propylene-based resin (B) having a specific range of MFR. In addition, component (A) and component It is important to set the weight blending ratio of (B) within a suitable range.

  Hereinafter, the present invention will be described in more detail with reference to test examples and the like, but the present invention is not limited thereto.

1. Example of production of pellets (PET / PP blend product, PET single product, PP single product) PET (trade name; Unitika Polyester Resin MA-1340P, manufactured by Unitika Ltd., number average molecular weight = 18,000, Tg = 75 ° C. as a raw material resin , Melting point = 230 ° C., intrinsic viscosity = 0.57 dl / g) and PP (trade name; Novatec PP MG03E, manufactured by Nippon Polypro Co., Ltd., propylene / ethylene random copolymer, MFR = 30 g / 10 min) Each was heated until it melted. In addition, before heating and melt | dissolving PET, it heated for a time sufficient for the water | moisture content to evaporate beforehand.
The above-mentioned molten PET and PP are mixed so that the weight ratio is PET / PP = 7/3, 5/5, 3/7, and after sufficient mixing, a twin-screw extruder (trade name: LABOTEX30HSS, Inc. The mixture was extruded using Nippon Steel Corporation, and the extruded mixture was pelletized with a pelletizer.
Apart from the above, instead of using a blend of PET and PP, PET or PP single pellets were produced by the same method as above except that only PET or PP was used.

2. Example of preparation of medical container (Examples 1 to 3)
The PET / PP = 7/3, 5/5, and 3/7 pellets obtained above were each heated and fluidized, and single-layer bottles (inner diameter 15 mm, barrel thickness 0.7 mm by injection molding). And 48.7 mm in height (the height of the body is 30.5 mm)) (Examples 1 to 3).

(Comparative Example 1)
A single-layer bottle was produced in the same manner as described above except that a pellet made of a single PET was used in place of the PET / PP pellet.

(Comparative Example 2)
A single-layer bottle was produced in the same manner as described above, except that pellets made of a single PP were used instead of PET / PP pellets.

3. Evaluation of moisture permeability Filled bottles of Examples 1 to 3 and Comparative Examples 1 and 2 prepared above with 5 mL of purified water,
Samples 1 to 5 were prepared by sealing the mouth of each bottle with a cap. The cap used was manufactured by injection molding using polyethylene (trade name; Novatec LD LJ808, manufactured by Nippon Polyethylene Co., Ltd.) so as to fit into the mouth of the bottle.
Each specimen was stored at 40 ° C. ± 2 ° C. and relative humidity 20% ± 2%, and the weight of each specimen was measured at the start of storage and 1, 4, 7 and 14 days after the start of storage.
From the measured weight, the water vapor transmission rate was calculated based on the following formula 1, and the water permeability of the single layer bottle using the blend material was evaluated. The results are shown in Table 1 (Formula 1) Water vapor transmission rate (%) = (weight at start (g) −weight after storage (g)) / 5 (g) × 100

Sample 4 using the bottle of Comparative Example 1 (PET 100%) had the highest water vapor transmission rate, and the water vapor transmission rate gradually decreased as the mixing ratio of Sample 1, Sample 2, Sample 3 and PP was increased. From the result after 14 days, the water vapor transmission rate of specimen 4 using a bottle of 100% PET was 1.14%, but the water vapor transmission rate of specimen 1 using a bottle containing 30% PP was 0.67%. Met. Based on the above results, 14 days after the start of the test, if 30% PP is added to PET as a bottle material, the water vapor transmission rate can be reduced by about 40% compared to a PET 100% bottle. Is shown.
As a desirable standard for moisture permeability, when the moisture reduction rate after storage for 3 months at 40 ° C. and a relative humidity of 25% or less is about 5% or less of the initial weight, the moisture corresponding to the above criteria after 40 ° C. and 2 weeks later The reduction rate is about 0.78% or less. When the bottles of Examples 1 to 3 were used, all satisfied this criterion.

4). Preparation example of test piece (test pieces 1 to 3)
Each of the pellets of PET / PP = 7/3, 5/5, and 3/7 obtained above is heated and fluidized, and a plate (140 mm × 90 mm, thickness 1 mm) is produced by injection molding. What was cut | disconnected to 30 mm x 5 mm was used as the test pieces 1-3 of the L-menthol adsorption evaluation test mentioned later. The constituent components and mixing ratio of the test pieces 1 to 3 are as follows.
Test piece 1: PET / PP = 7/3
Test piece 2: PET / PP = 5/5
Test piece 3: PET / PP = 3/7

(Test piece 4)
A plate (140 mm × 90 mm, thickness 1 mm) was prepared in the same manner as described above except that a pellet made of a single PET product was used instead of the PET / PP pellet, and then the plate was cut into 30 mm × 5 mm, It was set as the test piece 4 of the L-menthol adsorption property evaluation test mentioned later.

(Test piece 5)
A plate (140 mm × 90 mm, thickness 1 mm) was prepared in the same manner as described above except that a pellet made of a single PP was used instead of a pellet of PET / PP, and then cut into 30 mm × 5 mm, It was set as the test piece 5 of the L-menthol adsorption property evaluation test mentioned later.

5. Evaluation of L-menthol adsorptivity Glass ampules (capacity: about 8 mL) were filled with 6 mL of 0.01% by weight L-menthol aqueous solution, and two test pieces 1 to 5 were immersed and sealed (sealed). Samples were designated as specimens A to E. Each specimen was stored at 50 ° C. ± 2 ° C., and the content of L-menthol in the aqueous solution was measured at the start of storage and 1, 4, 8 and 12 days after the start of storage. The L-menthol content was quantified by high performance liquid chromatography (HPLC). HPLC measurement conditions are as follows.
(HPLC measurement method)
Detector: differential refractometer (cell temperature: constant temperature around 40 ° C)
Column: A stainless tube having an inner diameter of 4.6 mm and a length of 15 cm is packed with 5 μm of octylsilylated silica gel for liquid chromatography (OC12S05-1546WT (A-202) YMC).
Column temperature: constant temperature around 40 ° C. Mobile phase: water / acetonitrile mixture (1: 1)
Flow rate: Adjust the flow rate so that the internal standard substance retention time is about 5 minutes.

In quantifying L-menthol, the amount of L-menthol was calculated based on the following formula 2, and then the residual ratio of L-menthol was calculated based on the following formula 3. The results are shown in Table 2.
(Formula 2) L-menthol amount (vs. display rate%) = L-menthol weighed for quantification (mg) × QT / QS × 10
In (Formula 2), QT indicates the peak area of L-menthol, and QS indicates the peak area of the internal standard substance.
(Formula 3) L-menthol residual ratio (%) = average display ratio after change over time (%) / average display ratio at start (%) × 100
Note that the display ratio is a percentage (%) of the amount of the component contained in the prepared specimen with respect to the display amount of a certain component.

In specimen D using test piece 4 (PET 100%), L-menthol in the aqueous solution continued to maintain a residual rate of about 100% even after days, but specimen A, specimen B, specimen C, and PP The residual ratio of L-menthol in the aqueous solution decreased as the blending ratio was increased. This has shown that the adsorption | suction to the bottle of L-menthol increases by raising the mixture ratio of PP as a bottle material.
Considering the cooling effect of L-menthol, the residual rate when the adsorption to the bottle reaches a plateau is desirably about 50% or more. It is presumed that any of the single-layer bottles composed of the mixing ratios of the test pieces 1 to 3 satisfies the above criteria.

  From the results of “3. Evaluation of moisture permeability” and “5. Evaluation of L-menthol adsorptivity”, the use of a blend of PET and PP as a container material suppresses the evaporation of moisture in the filled chemical. It was found that it can be used as a container capable of suppressing the adsorption of the fat-soluble drug to the container. Although these effects depend on the physical properties or substances contained in the internal solution, the maximum effects can be exhibited by appropriately controlling the blending ratio of PET and PP. In particular, even when the blending ratio of PP is low, moisture permeation can be remarkably suppressed. Therefore, when taking into account the solute container adsorption, the blending ratio of PET / PP is PET / PP = 5 / 5-7. / 3 is most desirable.

  The medical container of the present invention is capable of suppressing moisture permeation of the chemical liquid filled in the container to the outside of the container and suppressing adsorption of the solute contained in the chemical liquid to the container. Can be widely applied to medical containers for which, for example, an eye drop container, a nose container, or an ear container is widely used.

Claims (7)

  Single-layer resin composition layer containing polyethylene terephthalate (A) having an intrinsic viscosity of 0.5 to 0.9 dl / g and a propylene resin (B) having a melt flow rate (MFR) of 2 to 60 g / 10 min A medical container consisting of   The container according to claim 1, wherein the weight ratio of the component (A) and the component (B) is (A) / (B) = 3/7 to 7/3.   The container according to claim 1, wherein the weight ratio of the component (A) to the component (B) is (A) / (B) = 5/5 to 7/3.   Single-layer resin composition layer comprising polyethylene terephthalate (A) having an intrinsic viscosity of 0.5 to 0.9 dl / g and a propylene resin (B) having a melt flow rate (MFR) of 2 to 60 g / 10 min. A medical container consisting of   The medical container according to any one of claims 1 to 4, wherein the medical container is an eye drop container, a nasal drop container, or an ear drop container.   Single-layer resin composition layer containing polyethylene terephthalate (A) having an intrinsic viscosity of 0.5 to 0.9 dl / g and a propylene resin (B) having a melt flow rate (MFR) of 2 to 60 g / 10 min A method of suppressing moisture permeation of the chemical liquid filled in the container to the outside of the container and suppressing adsorption of a solute contained in the chemical liquid to the container by using a medical container comprising: Melting step of heating and melting polyethylene terephthalate (A) having an intrinsic viscosity of 0.5 to 0.9 dl / g and propylene resin (B) having a melt flow rate (MFR) of 2 to 60 g / 10 min. ,
A kneading step of kneading the component (A) and the component (B) obtained in the melting step;
A pelletizing step of cooling and pelletizing the resin composition containing the component (A) and the component (B) obtained in the kneading step,
A molding step for injection molding by melting the pellet of the resin composition obtained in the pelletizing step,
The manufacturing method of the medical container in any one of Claims 1-5 containing these.