JPH0422491A - Preparation of pyrogen free water - Google Patents

Abstract

PURPOSE:To perfectly remove an endotoxin especially difficult to remove among pyrogens by transmitting pyrogen-containing water through an adsorbent layer and a precise filter membrane module and subsequently transmitting the same through an ultrafiltration membrane module. CONSTITUTION:Tap water is transmitted through a packed bed of an adsorbent represented by activated carbon to adsorb and remove residual chlorine or org. matter (offensive smell components such as a mold smell or pyrogens). Further, the fine particles such as iron rust or bacteria in tap water are prevented from transmission by a precise filter membrane module. An ultrafiltration membrane module perfectly blocks pyrogens not remove by the adsorbent and the precise filter membrane module. Therefore, as the ultrafiltration membrane module, one showing fractionating characteristics (a nominal fractionation mol.wt.(MW) being an MW showing an inhibition ratio of 90% on the basis of polyethylene glycol is about 10000) or one required in characteristics on a further small MW side is used.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention relates to a method for producing pyrogen-free water. More specifically, the present invention relates to a method for producing pyrogen-free water using a membrane permeation method.

[Prior art] and [Problem to be solved by the invention]
In the production of pure water used for pharmaceutical injections, it is necessary to remove a substance generally called a pyrogen (pyrogen), and conventionally this has been done by distillation. Recently, methods using reverse osmosis membranes have also been adopted, and these two methods are legally recognized.

However, the distillation method requires a heat source;
Manufacturing costs are high due to high energy consumption, and the reverse osmosis membrane method requires equipment such as circulation pumps that can generate high water pressure.

In addition to the above two methods, methods for removing pyrodiene have been proposed, including methods using adsorbents such as activated carbon, and methods using adsorption effects such as membranes made of polyolefin materials.
Although these adsorption methods remove most of the pyrodiene, they do not completely prevent it.

By the way, there are many substances called pyrodiene, but one substance that is said to be particularly difficult to remove is a substance called 1'endo-xin'' which is a low molecular weight pyrodiene.

Endotoxin is a polysaccharide derived from Durham-negative bacteria, and is generally used synonymously with pyrodiene.

An object of the present invention is to provide a method for producing pyrogen-free water that makes it possible to completely remove pyrodiene, including endotoxin, by an inexpensive method.

[Means to solve the problem]

This object of the present invention is achieved by passing pyrodiene-containing water through an adsorbent layer and a precision filtration membrane module, and then passing it through an ultrafiltration membrane module to produce pyrogen-free water.

Basically, the removal of endotoxins and other pyrogenes can be carried out using only the ultrafiltration membrane module, but in that case, the flow rate decreases significantly due to clogging, so first use tap water. The pyrodiene-containing water is passed through the adsorbent layer and the precision filtration membrane module in any order, generally in this order.

Permeation through a packed bed of adsorbent, typically activated carbon, adsorbs and removes residual chlorine and organic substances (odor components such as musty odor, pyrodiene, etc.) in tap water. In addition, fine particles such as iron rust and bacteria are blocked when passing through the precision membrane module. This precision membrane module is
In order to keep the load on the ultrafiltration membrane module as small as possible, the pore diameter is approximately 0.01-0.05 μm, and the pure water permeability coefficient is 100aJ/aiT・(kg/ci)・h.
A precision membrane with a diameter of r or higher is required.

In the ultra-permeable membrane module, pyrodiene that cannot be completely removed by the adsorbent and the ultra-permeable membrane module is completely blocked. Therefore, as an ultrafiltration membrane module,
Those that exhibit fractionation characteristics equivalent to those shown in the graph of Figure 1 (nominal fractional molecular weight, which is the molecular weight when showing a rejection rate of 90% based on polyethylene glycol, are approximately 10,000), or those that exhibit characteristics on the smaller molecular weight side. What is required is used.

In addition, in order to make it more compact, the processing flow rate per unit volume must be large, so the outer diameter is approximately (1,
3-0.6ff1m, preferably about 0.4-0.5rn
m, wall thickness is approximately 0.1. It is a hollow fiber membrane of about mm, and the pure water permeability coefficient (25°C, outer diameter standard) is 5ad/a+t.
(kg/d)·hr or more is required to be used as a module. As membrane materials for such hollow fiber membranes, polysulfone, polyvinylidene fluoride, etc. are used.

[Effect of the invention] Complete removal of endotoxin, which is particularly difficult to remove among pyrogenes, is achieved by passing pyrodiene-containing water through an adsorbent layer and a precision membrane module, and then passing it through an ultrafiltration membrane module. can do. Furthermore, this removal method does not require any cost for the treatment method itself or the treatment equipment, and since it is a sip-through type, it has the advantage that almost no water or energy is wasted. Furthermore, this method, which allows pyrogen-free water to be easily produced using a simple device, also allows for miniaturization of the device, so it can be applied at the raw water supply end, that is, at the point of use.

〔Example〕

Next, the present invention will be explained with reference to examples.

Example A spinning dope consisting of 84 parts by weight of aromatic polysulfone, 15 parts by weight of dimethylformamide and 1 part by weight of polyvinylpyrrolidone was prepared using ethanol as the core liquid and an outer diameter of 0.5 m.
m, extruded from a double annular nozzle with an internal diameter of 0.3rnvn,
Wet-dry spinning.

The obtained hollow fiber membrane with an outer diameter of 0.4 mm and an inner diameter of 0.2 mm has the fractionation characteristics shown in the graph of FIG.
J) and ]Oa(/cj(kg/a()·hr).

Endotoxin-containing water (regular tap water) was permeated through an ultrafiltration membrane module made using this hollow fiber membrane, and a limulus test was performed on the raw water and permeate, and endotoxin was detected in the raw water. However, it was not detected in the permeate.

(Limulus test) Caputo crab blood cell extract component (Limulus Ameb
This is a detection method that utilizes the gelation of ocyteLysate LAL) that specifically reacts with endotoxins, and uses a commercially available endotoxin detection kit (Mitsubishi Rayon product rim tester) with a detection sensitivity of 1.05 to 0.1.
ng/m12 By the way, when tap water is passed directly using only this ultra-filter hollow fiber membrane module, the flow rate decreases significantly due to clogging, but if the activated carbon layer and precision filter membrane module (
Regarding water treated with a membrane pore size of 0.04 μm, the decrease in flow rate was considerably suppressed. In other words, tap water (Fujisawa Municipal Water Supply)
When directly transmitted, the throughput per unit membrane area is 1
At 00cd/a#, the transmission coefficient is about 0.8-0.5
a#/aJ j (kg/a&)・hr or less, but for water treated with activated carbon layer and precision filtration membrane module, at 100 al/ffl,
Water permeability of 3 al/d・(kg/cn)・hr or more was maintained.

[Brief explanation of drawings]

FIG. 1 is a graph showing the fractionation characteristics of the ultrafiltration membrane used in the method of the present invention.

Claims (1)

[Claims] 1. A method for producing pyrogen-free water, which comprises passing pyrogen-containing water through an adsorbent layer and a precision membrane module, and then passing it through an ultrafiltration membrane module.