CH634661A5 - Powder for chromatographic separations - Google Patents

Description

This invention relates to a powder for chromatographic separations which can be used in the separation zone of chromatographs.

US Pat. No. 3,505,785 describes superficially porous Mi-i5 crospheroids which have an average diameter in the range from 5 to 500 μm and consist of an impermeable core and a multiplicity of single layers of colloidal inorganic particles of a medium size which surround the core in the range of 0.005 to 1.0. US Pat. No. 3,855,172 20 describes microspheroids which are porous throughout and have an average particle diameter in the range from 0.5 to 20 μm. They consist of colloidal inorganic refractory particles with an average diameter in the range from 0.005 to 1.0 [xm.

25 The use of microspheroids of this type for chromatography, in particular size exclusion chromatography, is generally known. In this application, porous microspheroids are used as filling material for the separation zone of the chromatograph. They separate 30 the components of a sample based on differences in the hydrodynamic size of the components. The molecular weight (MW) of the components can be calculated as a function of the hydrodynamic size. A graphical representation of the molecular weight fraction eluted at a given retention volume (VR) for a specific filler material shows that given a pore volume in the filler material, certain molecular weight fractions are completely excluded due to their large size and certain molecular weight fractions due to their small size pass through completely . Between these two extremes is a range of molecular weight fractions which are preferably retained or delayed by contact with the porous particles; Materials containing these molecular weight fractions can be fractionated through this special filler.

The actual working relationship in size exclusion chromatography is the molecular weight calibration curve, which is usually a logarithmic graphic representation of the molecular weight as a function of the retention or retention volume. Molecular weight calibration curves characteristically have a substantially linear part so that the molecular weight of a retained fraction of a sample can be accurately determined if the retention volume for that particular molecular weight fraction occurs in the near-left part of the molecular weight calibration curve and is less accurate, if it occurs outside of this linear range. Molecular weight calibration curves characteristically have linear parts that are in the log over approximately two decades. Extend molecular weight scale for a single pore-60 large. In order to obtain a calibration curve with a linear part which extends over more than two decades of the molecular weight scale, a chromatographic separation zone is usually used, which consists of numerous columns, each of which has a different pore size. As described in 65 "Know More About Your Polymer", published in 1976 by Waters Associates, Milford, Mass., One combines to expand the linear range of the molecular weight calibration curve in such a way that materials that

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contain a wide range of molecular weight fractions, separated and detectable, four or five columns, each having molecular weight calibration curves, the linear parts of which overlap.

Unfortunately, the expected linear molecular weight calibration does not occur. The straight line portion of the molecular weight calibration curve for the combined particles can be increased in this way, but the maximum appears to be only about three decades. This is often less than the molecular weight range found in normal sample compositions.

The powder according to the invention for chromatographic separations, for use in the separation zone of chromatographs, essentially comprising a multiplicity of separate, porous macro particles, each of which has an average diameter of 0.5 to 500 μm, is characterized in patent claim 1.

The term "average pore size" used here denotes the average pore size by volume. In order to reach the maximum range of the straight part of the molecular weight calibration curve, the pore sizes of the types of bimodal distribution must be about an order of magnitude apart. The term "bimodal pore distribution" used here is not to be understood as precluding the use of more than two types of particle size distributions, as long as adjacent distribution modes have essentially parallel linear, non-overlapping parts of their calibration curves, the mean pore volumes of each of the the two neighboring distribution methods are separated by an order of magnitude.

The macroparticles suitable for the purposes of the invention can be refractory particles, for example made of silicon dioxide or aluminum oxide, or they can consist of crosslinked polymer gels. In the preferred embodiment, the macroparticles are refractory macroparticles which consist mainly of silicon dioxide, the component of the bimodal pore distribution having the smaller mean pore diameter being 30 to 60%, preferably approximately 40 to 60%, in particular 40 to 55% of the total pore volume of the macroparticles in makes up the separation zone and a proportion of 45 to 55% is particularly preferred, while the rest of the total pore volume is contributed by the component of the bimodal pore distribution with the larger mean pore diameter. The separation zone can consist of a plurality of macroparticles, each of which has a bimodal pore distribution, or it can also consist of a plurality of macroparticles with the same pore distribution in each particle in combination with a plurality of macroparticles with a different pore distribution.

The patent also relates to the use of the powder according to the invention. This use is characterized in claim 7.

The invention is described below with reference to the figures.

1 shows a representative calibration curve of the molecular weight as a function of the retention volume in the log. Scale.

2 shows a calibration curve for the separation zone consisting of six different particles with different pore sizes.

FIG. 3 is a schematic illustration of a liquid chromatograph with the injection point 12 for the carrier liquid, the separation zone 13 and the detector 14 and shows in particular separation zones which consist of 1 and 2 separate columns.

4 shows a representative calibration curve for a bimodal and a polymodal separation zone.

Fig. 5 shows schematically partially cut open an embodiment of a completely porous macro particle with bimodal pore distribution.

6 shows schematically and partially cut open a second embodiment of a completely porous macro particle with a bimodal pore distribution.

7 shows schematically and partially cut open an embodiment of a superficially porous macro particle with a bimodal pore distribution.

Figure 8 shows a comparison of the calibration curve obtained using two of the particles shown in Figure 2 with non-overlapping particle size distributions with a calibration curve obtained using five of the particles shown in Figure 2, the particle sizes of which -divisions overlapped, was obtained.

FIG. 9 shows a calibration curve obtained using the bimodal particles shown in FIG. 6.

A chromatograph as schematically shown in FIG. 3 is used for the size exclusion chromatography. The material to be separated is injected into a carrier liquid stream at an injection point 12 and is fed under pressure through a chromatographic separation zone 13 to a detector 14. As they pass through the separation zone, the materials in the carrier medium contact the fill material in the separation zone, being retained for a period characteristic of their molecular weight (MW). After a certain time, after a larger volume of the carrier medium has passed through the chromatography column, the material temporarily retained by the filling material is eluted from the column. The detector determines when each component of the material leaves the separation zone.

The output signal of the detector is a characteristic peak, as is shown schematically in FIG. 4 below. 35 As separation zones for size exclusion chromatography, columns are generally used which are described with porous particles as described in US Pat. Nos. 3,505,785 and 3,855,172, or more recently with the macroporous microspheroids described in the US - Patent application 639 111 40 (June 15, 1976) are filled.

For the use of such filler materials, a typical relationship of log MG (a function of the hydrodynamic radius of the solute (solute hydrodynamic radius) as a function of the retention volume (VR) is shown by the single-solid line on the left side of FIG. 1 The limiting retention volume at point A is known as the total exclusion volume, which is determined by the maximum pore size available for penetration by the solutes, which are completely rejected from the eluate of the internal pore volume 50 (internal porosity elute) with this retention volume The solutes that correspond to this molecular weight and a higher molecular weight are not fractionated by the system, point B represents the volume of the species that completely penetrate the inner 55 pores of the filler material and is known as the total permeation volume. that this and a lower molecular weight weight, can practically not be fractionated by this separation system. The difference between the retention volumes A 60 and B represents a partial permeation of the solutes, and the separation takes place within this volume. The difference between the retention volume at B and the retention volume at A is a function of the total internal pore volume of the filler. Between the retention volumes at A and B there is an approximately linear region of the log MG curve as a function of the retention volume (points C to D), which is represented by the following equations:

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VR = Q-Q, • log MG and

MG = Dje-D2VR

(1)

(2)

C2 is the slope of the straight part of the calibration curve (in ml / decade MG) and Q is the section of this straight part. To obtain information about the molecular weight from this calibration curve, test chromatograms and equation 2 above are used. Dj denotes the section of this linear part of the calibration curve and D2 its slope. These equations are generally known to the person skilled in the art and are widely used for the characterization of macromolecules.

The additive characteristics of two equal columns used in size exclusion chromatography are well known. As shown in Fig. 1, connecting two identical columns (same particles, same length) with identical calibration curves, shown by the two solid lines, is tantamount to doubling the length of a single column. As shown in the figure, connecting these two columns increases the total available pore volume and thus increases the range of retention volume between total permeation and total exclusion, but maintains the same molecular weight fraction range. As shown in Fig. 1, when two columns are connected, the range of the molecular weight fraction remains at about 3,000 to 80,000, although the retention volume is doubled. The calibration curve for the combination of the two columns is shown by the dashed curve. The additive function that describes this relationship is

C2 = S (C ^ l i

D2 = 1/2 (1 / D2);

or (3) (4)

The polymer fractionation is usually carried out with fillings which have the widest possible pore size distribution. This is normally achieved by connecting several columns of different pore sizes and thereby forming a separation system that covers the molecular weight range of interest. Figure 2 shows a series of molecular weight calibration curves for six different chromatographic separation zones, each of which is filled with porous silica particles with different pore sizes. The designation and the average pore volume for these six particles are given in the following table.

designation

1 PMS-50

2 PMS-300

3 PMS-600

4 PMS-800

5 PMS-1500

6 PMS-4000

Pore size (Â) 60 125 195 300 750 3500

These particles were made according to the procedures described in U.S. Patent Application 639,111 (June 15, 1976) and U.S. Patent 3,782,075.

The bar diagrams on the right in Fig. 2 indicate the straight line area of each calibration curve. To achieve a straight line combined calibration curve spanning a molecular weight range from 103 to 106, a combination of six columns would typically be used, each consisting of the individual particles corresponding to the six diagrams.

The relationship given in equation 3 is now used to determine the accuracy, versatility and suitability of the size.

to improve the exclusion process. This relationship predicts a hitherto unrecognized phenomenon that a series of columns with substantially overlapping straight molecular weight fractionation areas (i.e. straight parts) should not be used to achieve a wide linear relationship between log MG and retention volume. Instead, columns with only two pore sizes should be used, so that the straight parts of the molecular weight curve do not overlap depending on the retention volume. As a result, a much larger linear range is obtained in the calibration curve. As representatively shown in Fig. 4, a polymodal pore distribution in the separation zone gives a narrow straight part on the molecular weight calibration curve, while a 15 bimodal distribution gives a much larger linear part. The calibration curve for the polymodal distribution does not encompass the entire molecular weight distribution of the sample within its rectilinear range, whereas the calibration curve for the bimodal distribution does.

The advantage of using chromatography columns with a bimodal pore distribution, regardless of whether columns with a uniform pore size are connected or columns that contain a physical mixture of particles that have two pore sizes, can be seen from FIG. 4. Molecular weight calibration curves of the type which the bimodal pore size distribution shows are particularly preferred when attempting to characterize a polymer with the type of molecular weight distribution shown in the illustration below.

Fig. 8 shows a quantitative comparison of a polymodal pore size distribution with the system of the bimodal pore size distribution. This figure shows a polystyrene calibration curve for a polymodal and a bimodal separation zone. The group of columns used to produce the polymodal distribution is filled with a filler, which is indicated in Figs. 2, 4, 4, 5 and 6. The individual columns have significantly overlapping calibration curves as in the usual mode. The approximate rectilinear region of the calibration curve (the dashed line is the rectilinear adjustment) of this combined group of wide pore distributions comprises only 2.5 molecular weight decades. In contrast, the bimodal distribution shown in Fig. 8 obtained by connecting columns of only two pore sizes (that of particles 1 and 5 in Fig. 2) gives a 45 straight molecular weight calibration curve that spans more than four decades of molecular weight.

In order to achieve these surprising and improved results, the individual calibration curves for the two pore sizes used in the bimodal distribution must not overlap. This is achieved by choosing particles with the appropriate pore size. The mean pore sizes of the bimodal distribution should be about an order of magnitude apart. With this bimodal path, linear calibration curves are obtained that span up to five decades of the molecular weight range. With a trimodal arrangement of the same type, straight-line parts of the calibration curve that span up to seven decades of the molecular weight range could be obtained. Apart from molecular weight calibration curves, which do not overlap, the inner pore volume of the two distribution modes must be such that the straight-line parts of the calibration curves run essentially parallel. The expression “essentially parallel” means that the shapes of the straight parts of the calibration curves do not have to run exactly parallel, provided that a certain deviation from the straightness can be accepted. For example, FIG. 8 shows that the overlapping polymodal calibration curve, which represents the state of the art, is far from being rectilinear over the predicted range.

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When 30 to 60%, preferably 40 to about 60%, especially about 40 to 55% and, which is particularly preferred, contain about 45 to 55% of the total pore volume of the macroparticles in each separation zone in the component of the bimodal pore distribution with the smaller mean pore size are, while the rest is accounted for by the component with the larger mean pore size, the straight-line parts of the individual calibration curves are essentially parallel. 9 illustrates the deviation from the straightness in the calibration curve when the ratio of the pore volumes is 40:60. In the particularly preferred embodiment, however, each component of the bimodal pore distribution should account for approximately 50% of the total pore volume of the macroparticle in the separation zone in order to reduce the deviation from the straightness in the calibration curve.

The best results are obtained if fillers with a very narrow pore size distribution are used. The pore size distributions of each bimodal system should be 1.0 or less (2ô), as the usual log-normal diagrams of mercury porosimetry show. Ranges of 0.5 (26) are preferred. Within these ranges, the pore size distribution is an insignificant factor in determining the D2 value of the calibration curve and the internal volume of the particles is decisive in determining the D2 value of the calibration curve. If the pore size distribution is larger than the values mentioned above, the interrelation of pore size distribution plus internal volume determines the slope of the calibration curve.

The bimodal pore distribution used according to the invention can be achieved by one of two methods. The bimodal pore distribution can be adjusted by a large number of microparticles, all of which have a bimodal pore distribution. In this case, a single column, as shown in the upper part of FIG. 3, can be used. However, the bimodal pore distribution can also be set by using a large number of macro particles which have a uniform pore distribution and a large number of macro particles with a different pore distribution. Although particles with different pore size distributions can be mixed in one column, the filling of these columns is less expedient. It is best to use two or more columns, each filled with particles of a certain type.

Individual particles with the pore size desired to achieve the bimodal pore distribution can be produced by the processes described in the above-mentioned patents and patent applications. Polymeric gels, alumina and the wide range of refractory particles mentioned in these patents and patent applications can be used, however silica is the preferred material, especially for chromatographic separations. Particles with a bimodal pore distribution can be either completely porous or superficially porous macro particles. The term “macro particle” used here means the composite macro particle (either completely or superficially porous) with an average diameter in the range from about 0.5 to 500 μm. The fully porous particle is shown in FIG. 5. This macro particle 15 has an average diameter of 0.5 to 500 [im. Macroparticles with an average diameter of approximately 5 to 50 μm are preferred. The macroparticle consists of a large number of microparticles 16, each having an average diameter in the range from 0.005 to 1.0 μm, preferably from approximately 0.005 to 0.5 μm. The individual microparticles in turn consist of a multiplicity of ultra-microparticles 17 with an average diameter in the range from 1.0 to 30.0 nm, preferably from 2 to 20 nm. Micropores 18 are present between all microparticles and micropores 19 are present between all ultra-microparticles In general, these particles can be of any shape, but the spherical shape is preferred so that the macroparticles are actually macrospheres, the microparticles are microspheres and the 5 ultra-microparticles are ultra-microspheres.The spherical shape of these materials improves their performance in chromatography columns.

As an alternative, as shown in FIG. 6, the fully porous macroparticle 15 can consist of a core 20 which consists of a multiplicity of ultramicroparticles 21 with an average diameter in the range from 1 to 30 nm and a skin which consists of a multiplicity of microparticles 22 each having a diameter in the range of approximately 0.1 to 1.0 µm or, preferably, 0.1 to 0.5 µm. The completely porous macroparticles produced by the processes known today preferably have a diameter in the range from approximately 0.5 to 50 μm.

An embodiment of a superficially porous macro particle is shown in FIG. 7. This macroparticle 22 has a diameter in the range from 0.5 to 500 μm, preferably from 5 to 50 μm, and consists of an impermeable macro core 24 and a shell composed of a plurality of identical single layers made of the same colloidal inorganic microparticles 25 are interconnected and surround the core 25. Each microparticle has an average diameter in the range of 0.005 to 1.0 µm, or preferably 0.1 to 0.5 µm and accounts for about 0.2 to 25% of the total volume of the macroparticle. The microparticle can be shown in FIG. 5 microparticles shown, which consist entirely of ultra-microparticles, or the same as the microparticles shown in FIG. 7, which consist of an impermeable microcore 27 and a shell composed of a multiplicity of identical single layers of the same colloidal inorganic ultra-microparticles 28 which have the core 35 In both cases, ie in the case of the completely porous and the superficially porous particles, the pores between the individual microparticles in the macroparticle are referred to as macropores 30, which represent a type of bimodal pore distribution, while the pores between the individual Ultramicroteil-40 chen are referred to as micropores 31, which is the other type of bimodal pore distribution tell. According to the more recent terminology, the pores of the size referred to here as "micropores" are referred to as "mesopores".

45

example 1

The production of "pellicular" particles with a bimodal pore size distribution is described below. Such a structure is shown in Fig. 7.

50 75 g of the chromatographic support “Zupax” (manufactured by the applicant) (<37 [im) were gently stirred for 30 minutes with 800 ml of 0.5% cleaning solution for laboratory equipment “Lakeseal”. The excess solution was removed by decantation, followed by washing with distilled water. These measures were repeated seven times. The powder obtained was then filtered on a coarse sintered glass filter and air dried. The dry powder was then placed in a coarse sintered glass funnel of 7.6 cm in diameter and stirred for 5 minutes with 100 ml of a 0.5% solution 60 of the antistatic agent and mold release agent “Zelec DX” (manufactured by the applicant). The treated beads were filtered off and then washed twice with 200 ml of distilled water and dried in a funnel under reduced pressure.

65 The beads were then coated with 100 ml of 10% silica sol, made from the product "Ludox AS" (silica particles of approximately 140 Â particle size, manufactured by the applicant) (125 g of 30% silica in "Ludox AS")

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distilled water diluted to 400 g), treated. The mixture of pearls and silica sol was left in the funnel for 15 minutes with frequent gentle stirring. The excess silicon dioxide "Ludox" was then filtered off and the wet cake obtained was washed four times by gentle slurrying with about 400 ml of tap water and filtration. The cake was then left to air dry in the filter under vacuum. This material was then dried for one hour at 150 ° C. in a hot air cabinet. A small sample was taken to measure the surface.

The treatment described above with the antistatic agent “Zelec DX” and the silica sol was repeated three more times, a crust of the silica sol ultrami-sized particles having a particle size of 140 Â being formed on the surface of the 2000 Â large silicon dioxide micro-particles which originally formed the crust of the particles of the chromatographic support «Zipax». The final particles were dried and heated at 650 ° C for 2 hours to burn out the organic interlayer and sinter the particles to a mechanically stable state. This sintered sample was then left to stand in a large excess of 0.001 molar ammonium hydroxide for 2 hours with frequent stirring. The particles were then washed twice with a large excess of distilled water by decanting, filtered on a coarse sintered glass funnel, air dried and heated in a circulating air bath at 150 ° C for 2 hours. The final material was sieved dry with stainless steel sieves to give 45 g of a fraction of particle size <38 µm.

The surface area of the products obtained during the synthesis steps was measured by the nitrogen flow method. The following results were obtained:

Sample surface, m2 / g

Original chromatographic 0.89, 0.99

«Zipax» carrier

First treatment with colloidal 2.03, 2.09

"Ludox AS" silicon dioxide

Second treatment with colloidal 2.35, 2.46

dalem silicon dioxide «Ludox

AS »

Third treatment with colloidal 3.07 3.01

"Ludox AS" silicon dioxide

Fourth treatment with colloidal 3.38, 3.50

"Ludox AS" silicon dioxide

Sintered at 650 ° C for 2 hours 2.67, 2.67

Final rehydrated Ma- 2.85, 2.86

material

The pore measurement for this sample by mercury porosimetry showed three breakpoints in the mercury intrusion curve, one at about 10 (im, which represents the penetration of mercury between the individual particles, a breakpoint at about 0.07 | xm (700 Â), the represented the macropores between the sol microparticles in the crust of the original chromatographic support «Zipax», and a kink at around 0.006 [xm (60 Â), which represented the pores between the 140 Â ultramicrosol particles, which were produced according to the method described here in many layers were applied to the original chromatographic carrier “Zipax.” The following volumes were used for the bimodal pore distribution:

Macropores (700 Â) 0.011 cm3 / g Micropores (60 Â) 0.014 cm3 / g

These values show that the final particles had the desired bimodal pore design with a size difference of about a decade between the two different pore sizes and approximately equal pore volumes for each pore size.

5 Example 2

Particles of the type shown in FIG. 6 can be produced as follows: 15 g of porous silicon dioxide microspheres (PSM-40; pores of 47 Â), produced according to the applicant's US Pat. Nos. 3,782,075 and 3,855,172, were treated with io200 ml of 0.001 molar ammonium hydroxide, left to stand for 10 minutes with occasional stirring and centrifuged in a 250 ml polyethylene bottle for 2 minutes (from the beginning) at about 2000 rpm. The clear supernatant was decanted. 100 ml of a 0.5% solution of the antistatic agent “Zelec DX” adjusted to pH 7 with ammonium hydroxide were added to the wet cake. The system was gently slurried and then left to stand for 10 minutes with occasional gentle stirring. The resulting mixture was centrifuged for one minute in the manner described above. The 20 excess solution of the antistatic agent «Zelec DX» was decanted. The wet cake was washed twice with 200 ml of distilled water (adjusted to pH 7 with ammonium hydroxide) by gently slurrying, centrifuging for 1 minute and decanting.

25 To these treated particles were added 50 ml of a 5% (weight) silica sol mixture adjusted to pH 8 of 2000 Â. (The sol can be prepared by the method described by W.Stober, A.Fink and E. Boh in J. Colloid, Inter. Sci. 26 (1968) 62). The mixture was carefully slurried for 30 and occasionally stirred for 10 minutes. This mixture was centrifuged and decanted in the manner described above. The excess sol was held back. The coated beads were then washed twice with 200 ml of distilled water (pH 7) by slurrying, centrifuging and decanting. The liquid decanted on the second wash in this treatment was clear. The wet cake was then filtered on a 3 (xm-filter ("Nucle-pore")) and dried for 2 hours in a warming cabinet with air swirling at 150 ° C. The sample was then baked for 40 hours in a muffle furnace at 700 ° C. A small amount of this material was examined under the scanning electron microscope, and it was found that the surface of the original beads was covered with the silica sol of 2000 Â particle size, and there were no uncovered spots 45 on the particles.

After the fired silica particles were hydrolyzed overnight in 0.01 molar hydrochloric acid and the acid removed by washing with distilled water, a second layer of 2000 Å silica sol was applied to the 50 PSM particles in the manner described above. The material was treated again with the antistatic agent “Zelec DX” and then with the 2000 Å sol (25 ml “fresh” sol plus excess sol recovered from the first treatment) in the manner described above. Examination of this material with the scanning electron microscope revealed that the second coating was layered in the desired manner. Very few bare spots were visible on the beads and very little bridging of particles was found.

60 A third, fourth, fifth and sixth treatment of the beads was carried out in essentially the same manner as described above to form the desired crust of 2000 µm diameter silica sol particles on the particles. These treated beads were baked at 65 750 ° C for one hour and rehydrolyzed in the manner described above by treatment with dilute acid. Examination of the final beads with the scanning electron microscope showed good coverage, but it was not possible

7

lent to recognize the exact thickness of the desired surface porous crust.

The calibration curve of log molecular weight as a function of the retention volume for a column of these particles of

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25 cm length and 0.62 cm inside diameter is shown in Fig. 9. Due to the difference in the internal volumes with these distribution methods, there is a certain deviation from the straightness.

C.

5 sheets of drawings

Claims (7)

634 661 PATENT CLAIMS 1. Powder for chromatographic separations, for use in the separation zone of chromatographs, containing, essentially, a multiplicity of separate porous macro-particles, each of which has an average diameter of 0.5 to 500 [im, characterized in that the Powder has a bimodal pore size distribution, the mean pore size for each distribution mode being such that the straight parts of the molecular weight calibration curve for each pore size in the bimodal distribution do not essentially overlap, and each distribution mode has such a pore volume that these straight parts in the run essentially parallel, with the average pore sizes of the components of the bimodal distribution being approximately an order of magnitude apart and 30 to 60% of the total pore volume on the component of the bimodal distribution with the smaller average pore size and on the component of the bimodal distribution with the larger size m Average pore size accounts for 70 to 40% of the total pore volume. 2. Powder according to claim 1, characterized in that on the component of the bimodal pore size distribution with the smaller average pore size 40 to 55%, e.g. 45 to 55% of the total pore volume and on the component of the bimodal pore size distribution with the average pore size 45 to 60%, e.g. 45 to 55% of the total pore volume is eliminated. 3. Powder according to claim 1, characterized in that the macro-particles are superficially porous macro-particles with an impermeable core and a shell made of a plurality of identical single layers of colloidal micro-particles touching and surrounding the core and having a diameter of 0.005 to 1.0 [ im, e.g. 0.1 to 0.5 µm and 0.2 to 25% of the total volume of the macroparticle, the macroparticles being 5 to 50 µm in diameter. 4. Powder according to claim 3, characterized in that the macro particles mainly consist of silicon dioxide and on the component of the bimodal pore size distribution with the smaller average pore size 40 to 55%, e.g. 45 to 55% of the total pore volume and to the component of the bimodal pore size distribution with the larger average pore size 60 to 45%, e.g. 45 to 55% of the total pore volume is eliminated. 5. Powder according to claim 1, characterized in that the macroparticles are completely porous and each macroparticle consists of a large number of microparticles which have a diameter of 0.005 to 1.0 μm, wherein macroparticles have a diameter of approximately 5 to 50 μm and wherein the macroparticles mainly consist of silicon dioxide and the component of the bimodal pore size distribution with the smaller average pore size 40 to 55%, e.g. 45 to 55% of the total pore volume and to the component of the bimodal pore size 60 to 45%, e.g. 45 to 55% of the total pore volume is eliminated. 6. Powder according to claim 1, characterized in that the macroparticles are completely porous and a core made of a large number of ultra-microparticles with a diameter of 1 to 30 nm and a shell made of a large number of microparticles with a diameter of 0.1 to 1. 0 [im, where the macroparticles have a diameter of 5 to 50 [im, wherein the macroparticles consist essentially of silicon dioxide and on the component of the bimodal distribution with the smaller average pore size 40 to 55%, for example 45 to 55% of the total pore volume and to the component of the bimodal distribution with the larger pore size 60 to 45%, e.g. 45 to 55% of the total pore volume is eliminated. 7. Use of the powder according to claim 1 for chromatographic separation, wherein a) the material to be separated is placed in a carrier medium, b) brings the carrier medium into contact with a separation zone which contains said powder, and c) determines the extent to which the materials are retained by the separation zone.