# US 7,745,499 B2 · Metal colloid solution

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- Number: US 7,745,499 B2
- Document ID: US7745499B2
- Status: Granted
- Kind: B2
- Application number: 10/564,837
- Filed: 2004-07-16
- Published: 2006-10-19
- Granted: 2010-06-29
- Earliest claimed: 2003-07-17
- Assignees: Asahi Kasei Medical Co., Ltd.
- Inventors: Tomoko Hongo; Naoko Hamasaki; Shoichi Ide; Fumihiko Yamaguchi; Mitsunori Kubozaki
- Web page: https://patentgrep.com/patent/US7745499B2

## CPC

- B01D 65/102: {Detection of leaks in membranes}
- A61K 33/24: Heavy metals; Compounds thereof
- A61K 33/242: Gold; Compounds thereof
- A61K 33/243: Platinum; Compounds thereof
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- B01J 13/0043: {containing elemental metal (for medical or diagnostical purposes A61K, G01N)}
- Y02A 50/30: Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
- B01D: SEPARATION (separating solids from solids by wet methods B03B, B03D; by pneumatic jigs or tables B03B; by other dry methods B07; magnetic or electrostatic separation of solid materials from solid materials or fluids, separation by high-voltage electric fields B03C; centrifuges, vortex apparatus B04; presses per se for squeezing-out liquid from liquid-containing material B30B9/02; treatment of water C02F, e.g. softening by ion-exchange C02F1/42; {arrangements of air intake cleaners in gas turbine plants F02C7/05} ; arrangements or mounting of filters in air-conditioning, air-humidification or ventilation F24F13/28)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- B01J: CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE

## Abstract

A colloid solution that exhibits storage stability and pH stability, being useful as viral substitute particles for use in an integrity test for virus removal membrane. In particular, a metal colloid solution characterized in that it comprises metal particles or metal compound particles of 1 to 100 nm average diameter, a water soluble high-molecular-weight dispersant having an N group and water and/or a water soluble organic solvent, the metal colloid solution being stable for a prolonged period of time and being stable in at least pH values ranging from 4 to 11.

## Claims

### Claim 1

A colloid solution of metal particles or metal compound particles being formed from one metal used in an integrity test for a virus removal membrane comprising:
(1) from 0.0001 to 0.1 wt % of metal particles or metal compound particles being formed from one metal having an average particle diameter of 15-40 nm,
(2) a water-soluble high molecular weight dispersant containing a pyrrolidone group,
(3) water, and
(4) an anionic surfactant and/or a chelating agent, wherein
all of the metal particles or metal compound particles of the colloid solution are formed from said one metal have an average particle size diameter of 15-40 nm, and
the colloid solution has the following properties (a) and (b):
(a) a maximum absorption wavelength after 180 days storage at room temperature and at a constant pH in a range from pH4 to pH11 which differs from the maximum absorption wavelength prior to storage by −2.0 nm to +2.0 nm, and
(b) a maximum absorption wavelength after one year storage at 50° C. and at pH5 which differs from the maximum absorption wavelength prior to storage by −2.0 nm to +2.0 nm.

### Claim 2 (depends on 1)

The colloid solution of metal particles or metal compound particles according to claim 1, wherein,
the metal particles or metal compound particles have a percent of variation in the particle diameter distribution of 30% or less, and
the colloid solution achieves a colloid recovery rate of 70% or more when the colloid solution is filtered through a collection test porous membrane and satisfies the following conditions:
(average pore diameter (nm) of the collection test porous membrane)−(average particle diameter (nm) of colloid)>10 nm.

### Claim 3 (depends on 1)

A method for producing a colloid solution used in an integrity test according to claim 1, comprising: adding a water-soluble high molecular weight dispersant containing a pyrrolidone group to the colloid solution, and
further adding an anionic surfactant and/or a chelating agent.

### Claim 4 (depends on 3)

The method for producing a colloid solution according to claim 3, further comprising:
dissolving a metal compound in a solvent, causing the metal particles to form by reducing the metal compound,
then adding a water-soluble high molecular weight dispersant containing a pyrrolidone group, and
further adding an anionic surfactant and/or a chelating agent.

### Claim 5 (depends on 1)

An integrity test method of a virus removal membrane for confirming the removability performance of the virus removal membrane comprising:
washing a virus removal membrane after use of the membrane for virus removal,
filtering the colloid solution according to claim 1 through the virus removal membrane which was used for virus removal, the colloid solution having a known absorbance at a maximum absorption wavelength,
measuring the absorbance of colloid solution at the maximum absorption wavelength after filtration, and
determining removability performance of the virus removal membrane based on the ratio of absorbance of the colloid solution measured before and after filtration.

### Claim 6 (depends on 5)

The integrity test method according to claim 5, wherein the virus removal membrane is a porous cellulose membrane.

### Claim 7 (depends on 5)

The integrity test method according to claim 5, wherein the virus removal membrane is a porous, thermoplastic synthetic polymer-membrane of which the surface is hydrophilized.

### Claim 8 (depends on 7)

The integrity test method according to claim 7, wherein the thermoplastic polymer is polyvinylidene fluoride or polyether sulfone.

### Claim 9 (depends on 5)

The integrity test method according to claim 5, achieving a colloid recovery rate of 70% or more when the colloid solution is filtered through a collection test porous membrane made of the same material as the virus removal membrane and satisfying the following conditions:
(average pore diameter (nm) of the collection test porous membrane)−(average particle diameter (nm) of colloid)>10 nm.

### Claim 10 (depends on 5)

The integrity test method according to claim 5, wherein the one metal is selected from the group consisting of gold, silver, platinum, rhodium, palladium, ruthenium, iridium, osmium, iron, and copper.

### Claim 11 (depends on 5)

The integrity test method according to claim 5, wherein
the average particle diameter of metal particles or metal compound particles is 15 to 40 nm and the percent of variation in the particle diameter distribution is 30% or less.

### Claim 12 (depends on 5)

The integrity test method according to claim 5, wherein the water-soluble high molecular weight dispersant containing the pyrrolidone group is poly(vinylpyrrolidone) or a poly(vinylpyrrolidone)copolymer.

### Claim 13 (depends on 6)

The integrity test method according to claim 6, wherein the surfactant is dodecylsulfuric acid or its salt.

### Claim 14 (depends on 6)

The integrity test method according to claim 6, wherein the chelating agent comprises at least one of tripolyphosphoric acid, polyacrylic acid, polyacrylic acid copolymer, ethylenediaminetetraacetic acid, and salts thereof.

### Claim 15 (depends on 5)

The integrity test method according to claim 5, wherein the colloid solution is filtered after the membrane is washed using an alkali solution, but is not neutralized with an acid.