Synthetic resins or natural rubbers -- part of the class 520 ser – Synthetic resins – Cellular products or processes of preparing a cellular...
Reexamination Certificate
1999-08-20
2002-11-19
Gorr, Rachel (Department: 1711)
Synthetic resins or natural rubbers -- part of the class 520 ser
Synthetic resins
Cellular products or processes of preparing a cellular...
C521S150000, C210S635000, C210S656000, C210S198200
Reexamination Certificate
active
06482867
ABSTRACT:
BACKGROUND OF THE INVENTION
The present invention generally relates to liquid chromatography and particularly to a packing material for liquid chromatography and a producing method thereof. More particularly, the present invention relates to an improvement of a producing method of a polymer packing material according to a two-step swelling polymerization process, as well as to a polymer packing material produced in accordance with such a process for liquid chromatography.
The packing material for high performance liquid chromatography (HPLC) is generally classified either as an inorganic packing material based on an inorganic carrier or as an organic polymer packing material on the basis of an organic polymer.
In actual use, inorganic packing materials based on silica gel are used most frequently. In reversed phase liquid chromatography, which occupies more than 60% of a total separation mode of HPLC, an alkylsilylated silica gel is used mainly, in which a surface of the silica gel carrier is subjected to chemical modification. While such conventional inorganic packing materials based on the silica gel exhibit an excellent separation characteristic and mechanical strength, there have been drawbacks in the conventional packing materials, such as low chemical stability or occurrence of an undesirable secondary retention effect caused by a silanol group remaining on the silica gel surface or by a metallic impurity contained in a silica gel base.
On the other hand, the organic polymer packing materials have an advantageous feature of good chemical stability and have been used for a packing material of size exclusion chromatography or ion exchange chromatography similarly to a silica gel packing material. The polymer packing materials can also be used in reversed phase liquid chromatography, particularly under a separation condition in which the use of silica gel packing material is not possible. Recently understanding of the separation characteristic of such organic packing materials has been increased, and there have been many reports showing that a separation characteristic superior to the separation characteristic of the silica gel packing material is obtained.
The polymer packing material, which is a crosslinked polymer, is generally classified either as that prepared from a natural polymer by a crosslinking process or as that synthesized by a polymerization process of a vinyl monomer. The representative examples of the former include packing materials prepared from polysaccharide derivatives such as agarose, dextran and mannan. These materials, however, may not be used for the packing material for HPLC because they generally suffer from a problem of a low withstand pressure. On the other hand, the synthetic polymer packing materials include polymers such as a polystyrene-divinylbenzene gel, a derivative thereof, a polymethacrylate gel and a polyacrylamide gel. Among the above synthetic polymers, the polystyrene-divinylbenzene gel and the polyacrylamide gel are chemically stable and used for the packing material in reversed phase liquid chromatography. It should be noted that these polymers are stable over a wide pH range as compared to the silica gel packing material and are not adversely affected by the metallic impurity. Such a synthetic organic polymer packing material is generally synthesized by mixing monomers together with a diluent and a crosslinking agent such that a porous structure can be formed. Fine pores can be formed when a good solvent is used for a polymer to be synthesized, while large pores tend to be formed when a poor solvent is used. Accordingly, a pore diameter can be controlled by choosing a combination of the diluent and the monomers. By using such a procedure, a spherical porous polymer packing material can be prepared in combination with a suspension polymerization process where its operation is simple.
However, such a polymer packing material has a structural problem with regard to distribution of the fine pores of a polymer particle. More specifically, the polymer packing material has a double pore structure having the fine pores and micropores, which arise in relation to a crosslinking structure of the polymer, wherein such micropores generally have a diameter less than 2 nm, unlike the fine pore (i.e., mesopore) of the silica gel packing material. Because of the existence of the micropores of the porous polymer particles, the extent of penetration of a solute molecule for the polymer packing material generally becomes large. The polymer packing material exhibits an inherent separation characteristic substantially different from that of the silica gel packing material when used for separation of a specimen in a column filled with this polymer packing material for chromatography. Since control for an effect of such micropores on resolution for chromatography is difficult, the use of the polymer packing material has frequently led to deterioration of resolution for sample analysis.
In actual HPLC analysis, an undesirable effect of such micropores is that retention of the specimen in the polymer packing material is strong. This effect takes place remarkably in a specimen with a large structure. In this case a width of a peak for the specimen becomes broad in a chromatograph, thereby reducing the number of theoretical plates. When the specimen passes through the micropores in a chromatography column, a smaller molecule than a size of these micropores is not subjected to a retention effect, while a large molecule is subjected to a retention effect caused by hydrophobic interaction with an inner surface of the micropores.
The undesirable effect for chromatography due to the micropores can be reduced by varying conditions of polymerization and crosslinking processes. That is to say, if a linear portion of the polymer synthesized by polymerization has the same length for each polymer chain and a length between crosslinking points becomes longer, this makes the micropore size bigger and the micropore size becomes approximately the same, thus allowing performance deterioration of the packing material to be inhibited. The degree of crosslinking can be lowered to extend the length between the crosslinking points. Because a lower ratio of crosslinking makes a strength of the polymer particle weak, it is impossible to use the above polymer for liquid chromatography as the packing material. It is required that the packing material should be prepared by controlling conditions and processes for polymerization and crosslinking reactions. For example, one of these control methods is an oxidation-reduction polymerization process at low temperature as polymerization of a monomer. By using this oxidation-reduction polymerization process, the micropore size becomes bigger and deterioration of the number of theoretical plates can be reduced, as compared to a conventional thermal polymerization in which the polymer particle can be generally prepared. Although this process is very useful in that the micropore size can be controlled, an improvement for the packing material performance is limited due to no change of a chemical nature of the inner surface of the micropores.
Thus, a problem of the micropore remains unsolved and hence the removal of the above problems remains as an important target of research of the polymer packing material.
SUMMARY OF THE INVENTION
Accordingly, it is a general object of the present invention to provide a polymer packing material for liquid chromatography and a producing method thereof wherein the foregoing problems are eliminated.
The inventors of the present invention have conducted various studies to achieve the aforementioned objects, and have discovered that a polymer packing material for liquid chromatography with an improved separation characteristic is obtained by modification of a chemical property of the inner surface of micropores of the polymer packing material and formation of a monodispersed system of the polymer packing material. In addition, an appropriate producing method for the polymer packing material is developed.
Accordi
Hosoya Ken
Kimura Tomohiko
Ohtsu Yutaka
Teramachi Masashi
Bagwell Melanie D.
Gorr Rachel
Kenyon & Kenyon
Shiseido Co. Ltd.
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