JPH0479957A - Wrapped test instrument - Google Patents

Abstract

PURPOSE:To efficiently obtain reliable results of a test without being disturbed by the possibility that adsorption instruments may be contaminated by pyrodiene by distributing wrapped test instruments each confirmed to be negative at a pyrodiene test. CONSTITUTION:A lid-equipped test tube A of capacity 2 to 10ml, a 1ml syringe B, a spouter C and a 0.2mum filter D are mentioned as typical examples of instruments, each of which is wrapped in a plastic bag while being negative at a pyrodiene test method. Both the test tube and the syringe may be of the same material, size and shape as general ones sold at any store. The spouter for scooping a small amount of adsorbent should preferably be made of glass or metal. Each of the instruments can be wrapped in any form only if contamination is prevented; a general wrapping material such as a plastic bag can be used. A filtering film made from cellulose acetate of hole diameter 0.2mum (effective filtering area 0.9cm<2>) can be used as the filter which is stored in housing made from polypropylene.

Description

[Detailed Description of the Invention] [Industrial Application Field] This invention relates to a packaged test device that has been confirmed to be negative in the pyrodiene test method and a kit that combines the device including the same. It is. The test equipment and kit of the present invention are useful for efficiently conducting pyrodiene adsorption tests, and can be used in medical-related industries such as pharmaceutical manufacturing and medical aid manufacturing by evaluating the performance of pyrodiene adsorbents and searching for suitable adsorption conditions. It can be used in the field.

[Conventional technology]

In the field of injectable drugs, it is well known that it is necessary to eliminate pyrodiene that enters the body and causes heat generation from the manufacturing process or product, and pyrodiene adsorbents for this purpose are also known.

However, in order to apply the pyrodiene adsorption removal method to individual chemical liquids, the pyrogen removal performance of the adsorbent,
A large number of tests are required, such as evaluation of the recovery performance of the target chemical, and search for adsorption treatment conditions to obtain suitable values for removal rate and recovery rate.

[Problem to be solved by the invention]

Adsorption tests are usually performed using batch or column methods, but if the equipment used for these adsorption tests, such as test tubes, may be contaminated with pyrodiene, reliable results may not be obtained. Needless to say.

By the way, it is extremely troublesome to have to purchase the necessary equipment from commercially available physical and chemical equipment, perform pyrogen removal treatment on each item, and only after confirming the results can the actual test be conducted. It is. In particular, for plastic utensils to which the pyrogen decomposition method by calcination cannot be applied, it is necessary to thoroughly wash them with pyrogen-free water after alkaline cleaning, and to confirm by a Rimuru test etc. that no pyrogenes are detected in the washing water. did not become.

Of course, instruments that are packaged and distributed in a sterile state have existed for some time. However, it goes without saying that sterile instruments do not guarantee the absence of pyrogen, and the use of sterile instruments does not reduce the laborious preparation work.

This invention was made in light of the above circumstances, and it is possible for a person who intends to remove pyrodiene from a drug solution etc. by adsorption to evaluate the removal performance, recovery performance, etc. of a pyrodiene adsorbent, and to determine the adsorption treatment conditions. The purpose of this invention is to provide a test device that allows reliable test results to be obtained efficiently without worrying about the possibility of pyrogen contamination of the adsorption tool. .

[Means to solve the problem]

As a result of intensive research, the present inventors have found that the above-mentioned problem is a test device that is packaged in a distribution-ready condition, and that the test device inside the package is negative for the pyrodiene test method upon inspection. Confirmed (LLrogen-n
The present inventors have discovered that the problem can be solved by a test device (Pinela device) characterized by being egatively wrapped (hereinafter abbreviated as "Vinella"), and have completed the present invention.

As a specific example of the Pinella device of the present invention, the volume is 1 to 1.
! , particularly preferably a 2-10af plastic Vinella container, a test instrument kit comprising a container, a syringe and a filter, a Pinella adsorption tool kit comprising a container, a syringe and a filter further combined with a pyrodiene adsorbent, a Pinella container and pyrodiene. Examples include an adsorption column kit formed by combining an adsorbent column.

In this specification, a Pinella device does not mean a device that is, as a matter of fact, pyrogen-free, but a test device that can be distributed in a packaged state and that has a test inside the package. It means a creation based on the technical concept of a device that has new technical value added by guaranteeing that the device will be negative when tested using some objective pyrogen test method. .

Methods for testing the presence or absence of pyrodiene in drugs include:
A fever test using rabbits is prescribed. However, in this invention, the test method to ensure that it is a Pinella device should not necessarily be based on this method, but rather the same test method that would be adopted by the user of the test device should be selected. For example, for users who adopt the Limulus Is test, the packaging test equipment
A negative result for the S test should be confirmed and displayed. Limulus HS test shows 1.3- as a side reaction.
This test also reacts with β-glucan, so even if the fever test using rabbits is negative, 1.3-β-
Contamination with glucan may result in a positive result.

Such 1,3-β-glucan-contaminated equipment, even if it is pyrogen-free in the rabbit pyrogen test, i.e., the equipment is in fact pyrogen-free, cannot be used with Limulus HS. It is of no use to users who adopt the test. This example highlights the technical difference between a "packaging device that tests negative using the pyrogen test method" and a device that is simply "in a pyrogen-free state." As an inspection method,
Known statistical quality control methods such as sampling inspection methods can be applied. Methods for removing positive substances in the pyrogen test from equipment and packaging materials include alkali treatment, washing with water, decomposition by heat treatment, decomposition by γ-ray irradiation, work in a clean room, etc., depending on the material, and are appropriately selected from known techniques. and can be used.

A representative example of the Pinella instrument of the present invention is shown in FIG. That is, a test tube with a lid (with a volume of 2 to 10)
Figure 1A), 1m syringe (Figure 1B), Supercil (
Figure 1 C), 0.2 tnrr filter (Figure 1 D
) (All are packaged in plastic bags with negative results for the pyrodiene test method.)

The material, size, shape, etc. of the test tube and syringe can be the same as normal commercially available products (for example, made of polystyrene).The spaticle used to scoop out a small amount of adsorbent should be made of plastic that repels water and is difficult to use. It is preferable that the packaging is made of glass or metal, and there are no particular limitations on the packaging as long as it can prevent contamination of the equipment.
Regular items such as plastic bags can be used. As the filter, for example, a precision filtration membrane made of cellulose acetate (effective filtration area 0.9 cmd) with a pore size of 0.24 and housed in a polypropylene housing with a diameter of 13 m can be used. These instruments may be similar in shape and supplied in sterile packaging. Some sterile packaging instruments are positive to the pyrodiene test, but by confirming that they are negative to the pyrodiene test through testing, it is possible to determine which instruments can be used in the kit of the present invention as Pinella instruments. be.

These Pinera devices may be supplied alone, or multiple Vinella devices may be combined and supplied to the secondary market as a Pinera adsorption tool kit. This Vinella adsorption tool kit may be further combined with a pyrodiene adsorbent. You can also do it.

Although the above kit is suitable for an adsorption test using a batch method, a Pinella adsorption equipment kit suitable for a continuous adsorption test using a column method can also be constructed using a Vinella instrument. An example is the combination of a Pinella test tube and a mini-column (with reservoir) pre-packed with pyrodiene adsorbent.

Such adsorption kits contain a suitable concentration, e.g.
If you combine specified alkali and/or acid aqueous solutions (pyrodiene-free), you will be able to create a drug aqueous solution PTT.
It is convenient because it can be used for adjustment and column regeneration.

The components of the kit may be individually sealed and combined, or a plurality of components may be sealed together for convenience.

A typical case where the test device of the present invention is used is a test in which pyrodiene is removed from a drug solution using an affinity adsorbent that selectively adsorbs pyrodiene.

An example of an affinity adsorbent is a bead-shaped gel made of cellulose or sepharose as a base material and bound to a ligand such as histidine.
The prior art described in Japanese Patent Application No. 712, Japanese Patent Application No. 1-320141, etc. can be referred to.

〔Effect of the invention〕

As a result of the present invention, the distribution of packaging test equipment that has been confirmed to be negative in pyrodiene tests will enable pharmaceutical manufacturers and others who attempt to remove pyrogen by adsorption to avoid the possibility of pyrogen contamination of adsorption equipment. Reliable test results can be obtained efficiently without being affected.

Combining multiple Vinella devices or Vinella devices and adsorbents to form a Pinella adsorption tool kit makes it more convenient to perform a series of adsorption tests and has the synergistic value of ensuring the reliability of the entire test. give birth to

〔Example〕

EXAMPLES Hereinafter, the present invention will be explained in more detail with reference to Examples, but the present invention is not limited to these Examples.

Example 1 A Pinella adsorption tool kit that can be used for 10 tests is constructed by combining the Pinella equipment consisting of (1) to (4) below and a pack containing 10 g of pyrodiene adsorbent (water-wet granular gel). do.

(1) Polystyrene 51 test tube with lid (Fig. 1 A) 20
Book (2) 20 1-piece syringes (Fig. 1 B) (3) 20 glass spatils (Fig. 1 C) (4) 10 syringe filters (0, 2 u) (Fig. 1 D) The Pinella instruments are packaged in individually wrapped bags as shown in FIG.

<Inspection method> Three types of liquids shown below ■～■ and the following (a) and (b)
Confirm that the packaging equipment is negative for the pyrogen test using the two pyrogen test methods shown below.

■ Pyrogen-free water, ■ Pyrogen-free phosphate buffer (pH 7, μ
=0.1), ■ 1% USA (human serum albumin) aqueous solution (a)
Limulus ES test, Wako (b) Limulus H
S test, Wako (Operating method) After contacting the liquid at room temperature, quantify by Limulus test using a toxinometer ET-201)
, compared to a blank test with no contact with the instrument. The following example uses 1 portion of liquid, 2 minutes of contact, and the unit of measurement is pg/a/.

<Example of results (negative)> Microfilter for syringe: Slowly pass the liquid through using a vinyla syringe.

(a) ES test (b) HS test blank → actual test Blank → actual test■ <1.5 → <1.
5 ＜2→〈2■ 〈1.4→＜1.4
＜2→〈2■ 12.6→13 180
→170〈Positive example (comparative example)〉 Sterile packaging plastic supertill (a) ES test (b) OS test blank → actual test Blank → actual test■ <1.4 → <2.
8 ＜2→〈6■ 12.6→41
180→510 Other testing methods can be used as needed.

<Example of kit usage> After firmly pushing the test tube lid into the main body by operating from outside the bag, open the bag and measure the weight. Open the pyrodiene adsorbent aluminum pack and cut the corner of the inner bag. Adsorbent-like 200cm (100~
Measure out 250 cm) into a test tube and weigh accurately. Using a syringe, add approximately 1@l amount of sample solution per 100 lag of adsorbent and close the lid tightly. Set the test tube in a suitable rotating device such as a round mixer, and stir at about 20 rpm for 1 hour. After stirring, leave the test tube still, suck up the supernatant with a syringe, remove the injection needle, connect a filter, and filter. The filtrate is collected in an unused test tube and used for measurement of pyrogen concentration and drug concentration. This kit has enough equipment to perform 10 tests, so you can use the same method to determine sample solution volume, drug concentration, and pH.
By repeating the test by changing the ionic strength, etc., it is possible to search for suitable adsorption conditions.

Example 2 A mini column kit consisting of a pyrodiene adsorbent mini column 1 with a 30117 reservoir 4 attached as shown in FIG. Both ends are closed with sintered filters 2.3, and inside the column is a pyrodiene adsorbent packed bed (about 80% of the natural sedimentation volume).
8-) is stored to prevent it from drying out. The container receives the analyte solution that is charged into the reservoir and flows down the column either naturally or under extrusion pressure. A cock for flow rate adjustment, a syringe for extrusion, a connecting pipe, etc. may be attached.

Example 3 25g of pyrodiene adsorbent is placed in a 500ml pinella container and a 250ml drug solution is added. Stir the liquid containing the adsorbent by rotating it with the lid on (1 to 4 hours), and separate the adsorbent and liquid using a microfilter unit (pore size 0.45M) that can be connected to containers on both sides. do. The filtrate is received in another 500 pinella container.

Examples 2 and 3 are useful for preparing a test solution of tens to hundreds of days required for a fever test using rabbits, which is adopted as a test method for pyrodiene against drugs.

[Brief explanation of the drawing]

FIG. 1 is an external perspective view showing an example of the Vinella instrument kit of the present invention, in which A is a test tube with a lid, B is a syringe, C is a supercil, and D is a syringe filter. FIG. 2 is a perspective view of the pyrodiene adsorbent mini-column taken out from the Pinella package. 1: Column body 2.3: Sintered filter 4: Reservoir

Claims (1)

[Scope of Claims] 1. A test device that is packaged in a distribution-ready condition, and that the test device inside the package has been confirmed to be negative for pyrogen testing by inspection. Characteristic test equipment. 2. The test device according to claim 1, which is a container having a volume of 1 ml to 1 liter. 3. The test device kit according to claim 1, comprising a container, a syringe, and a filter. 4. An adsorption instrument kit comprising the test instrument kit according to claim 3 further combined with a pyrogen adsorbent. 5. An adsorption column kit comprising a combination of the container according to claim 2 and a pyrogen adsorbent column. 6. The kit according to any one of claims 3 to 5, further comprising a combination of an aqueous alkali and/or acid solution.