WO2009017456A1

WO2009017456A1 - Pharmaceutical composition suitable for adsorption to the cell surface of pathogenic microbes

Info

Publication number: WO2009017456A1
Application number: PCT/SE2008/050901
Authority: WO
Inventors: Stellan Hjertén; Marie-Christine Hjertén; Torkel Wadström
Original assignee: Hjerten Stellan; Hjerten Marie-Christine; Wadstroem Torkel
Priority date: 2007-08-01
Filing date: 2008-07-30
Publication date: 2009-02-05
Also published as: EP2178540A4; EP2178540A1

Abstract

The present invention provides a pharmaceutical composition comprising a product for adsorption purposes, preferably in particulate or polymeric form, consisting of an in water insoluble or swelling support matrix wherein the support matrix is substituted with a hydrophobic entity which in turn is connected to a positively charged entity, other than said in water swelling or insoluble support matrix, and/or a product for adsorption purposes comprising a first support matrix connected to a hydrophobic entity and a second support matrix connected to a positively charged entity, and/or a product for adsorption purposes consisting of an in water insoluble or swelling support matrix wherein the support matrix is substituted with a hydrophobic entity and a positively charged entity, and/or a product for adsorption purposes consisting of an in water insoluble or swelling support matrix wherein the support matrix is substituted with a hydrophobic entity, and/or one or more preservatives, and/or one or more artificial antibodies and optionally a carrier. Also medical use of said product, use of said product for the manufacturing of a medicament for treating pathogenic microbes and therapeutic use of said product is provided.

Description

PHARMACEUTICAL COMPOSITION SUITABLE FOR ADSORPTION TO THE CELL SURFACE OF PATHOGENIC MICROBES

This invention concerns the technical field of pharmaceutical compositions comprising a product and uses of the same product.

Background

Most conventional antibacterials and antivirals are low-molecular weight compounds designed to enter the bacterial cell and the virus particle, which means that it is extremely difficult to design such substances since they are not allowed to enter the cells constituting our body or if they do so they must not be harmful for the normal activities of the human cells. The cost of the many different tests required in various forms is, therefore, enormous and therefore also the total cost of the development of conventional antibacterials and antivirals is extremely high.

There is known through WO2004110193 a product for adsorption purposes consisting of an in water insoluble support matrix wherein the support matrix is substituted with a hydrophobic entity which in turn is connected to a positively charged entity, a method for its manufacture, use thereof and applications of said product. It also relates to a product for adsorption purposes comprising a first support matrix connected to a hydrophobic entity and a second support matrix connected to a positively charged entity, a method for its manufacture, use thereof and applications of said product. It also relates to a product for adsorption purposes comprising a support matrix wherein the support matrix is substituted with a hydrophobic entity and a positively charged entity, a method for its manufacture, use thereof and applications of said product.

However there is a need for antibacterials and antivirals which are large entities and have the property not to penetrate the cell walls and if they do so they are chosen not to be harmful. Further the developmental cost would be much lower than for conventional antibacterials and antivirals as said antibacterials and antivirals do not enter the cells. Further, resistance against antibacterials and antivirals, which are well known for small molecules that penetrate the cell walls, can be avoided.

Summary of the invention

The present invention solves one or more of the above problems by providing according to a first aspect a pharmaceutical composition comprising a product for adsorption purposes, preferably in particulate or polymeric form, most preferred for oral use or intravenous use, consisting of an in water insoluble or swelling support matrix wherein the support matrix is substituted with a hydrophobic entity which in turn is connected to a positively charged entity, other than said in water swelling or insoluble support matrix, and/or a product for adsorption purposes comprising a first support matrix connected to a hydrophobic entity and a second support matrix connected to a positively charged entity, and/or a product for adsorption purposes consisting of an in water insoluble or swelling support matrix wherein the support matrix is substituted with a hydrophobic entity and a positively charged entity, and/or a product for adsorption purposes consisting of an in water insoluble or swelling support matrix wherein the support matrix is substituted with a hydrophobic entity, and/or one or more preservatives, and/or one or more artificial antibodies, and optionally a carrier. According to a second aspect of the invention medical use of a product for adsorption purposes, preferably in particulate or polymeric form, consisting of an in water insoluble or swelling support matrix wherein the support matrix is substituted with a hydrophobic entity which in turn is connected to a positively charged entity, other than said in water swelling or insoluble support matrix, and/or a product for adsorption purposes comprising a first support matrix connected to a hydrophobic entity and a second support matrix connected to a positively charged entity, and/or a product for adsorption purposes consisting of an in water insoluble or swelling support matrix wherein the support matrix is substituted with a hydrophobic entity and a positively charged entity, and/or a product for adsorption purposes consisting of an in water insoluble or swelling support matrix wherein the support matrix is substituted with a hydrophobic entity, and/or one or more preservatives, and/or one or more artificial antibodies is provided.

According to a third aspect of the invention use of a product for adsorption purposes, preferably in particulate or polymeric form, consisting of an in water insoluble or swelling support matrix wherein the support matrix is substituted with a hydrophobic entity which in turn is connected to a positively charged entity, other than said in water swelling or insoluble support matrix, and/or a product for adsorption purposes comprising a first support matrix connected to a hydrophobic entity and a second support matrix connected to a positively charged entity, and/or a product for adsorption purposes consisting of an in water insoluble or swelling support matrix wherein the support matrix is substituted with a hydrophobic entity and a positively charged entity, and/or a product for adsorption purposes consisting of an in water insoluble or swelling support matrix wherein the support matrix is substituted with a hydrophobic entity, and/or one or more preservatives, and/or one or more artificial antibodies, for the manufacturing of a medicament for treating pathogenic microbes, such as bacteria and viruses is provided. According to a fourth aspect of the invention therapeutic use of a product for adsorption purposes, preferably in particulate or polymeric form, consisting of an in water insoluble or swelling support matrix wherein the support matrix is substituted with a hydrophobic entity which in turn is connected to a positively charged entity, other than said in water swelling or insoluble support matrix, and/or a product for adsorption purposes comprising a first support matrix connected to a hydrophobic entity and a second support matrix connected to a positively charged entity, and/or a product for adsorption purposes consisting of an in water insoluble or swelling support matrix wherein the support matrix is substituted with a hydrophobic entity and a positively charged entity, and/or a product for adsorption purposes consisting of an in water insoluble or swelling support matrix wherein the support matrix is substituted with a hydrophobic entity, and/or one or more preservatives, and/or one or more artificial antibodies is provided. The supports themselves may also be hydrophobic, e.g. polystyrene with charged groups e.g. polystyrene beads with amino groups attached.

The substances proposed have the property to attach to the surface of the bacteria and the viruses and in doing so the bacteria and viruses cannot multiply or become inactive, nor can they interact, or only slightly, with the wall of human cells, i.e. these bioparticles are not inactivated. This attachment is based on hydrophobic interactions or/and electrostatic interactions or/and aromatic interactions, as described elsewhere in this application. It should be recalled that the more pathogenic the bacteria are the more hydrophobic is their surface, i.e. the stronger they are attached to the proposed antibacterial agent. Bioparticles, such as cells (including bacteria), viruses, fungi, spores, have a surface structure which exhibits many similarities, for instance they all have (a) a net charge which is negative and (b) hydrophobic groups on the outside and (c) carbohydrates on the outside. All types of bioparticles will accordingly be attached to a support containing hydrophobic or/and positively charged groups (ligands) and/or phenol groups independent of the method for the attachment of these groups and the choice of type of supporting medium. The same method can thus be employed for the attachement of all kinds of bioparticles, which makes the commercial production of the antibacterials, antivirals etc. more cost- effective since each method for the synthesis has been chosen to become applicable to all the described products, which makes their production more cost-effective since the same manufacturer can be used for most of the products described. The present invention deals with different strategies to take advantage of these three general surface properties of bioparticles to make pathogenic bioparticles non-pathogenic by forming complexes between pathogenic bioparticles and appropriate materials, particularly derivatized polymers which swell in aqueous solutions and particles (for instance cellulose), the selection of which among other things is based upon the above mentioned parameters (i.e. negative net charge, hydrophobic groups, and carbohydrates) to promote the formation of the nonpathogenic complex. This complex has such properties that the pathogenic biopartiele cannot multiply. When in this complex the pathogenic bioparticles cannot attach to the cell wall (of human cells). It has been speculated whether hydrophobic interactions which are involved in the formation of the complex are preceeded by van der Waals forces.

(1) One method to inactivate (or even kill) pathogenic bioparticles is to make them more negative and less hydrophobic, because following this treatment all cells in humans and animals only slightly interact with or repel these modified bioparticles, i.e. the native cells will not interact or only slightly interact with these modified bioparticles. In other words: The original pathogenic bioparticles have become harmless. The following observation shows that this is the way conventional antibiotics work: Bacteria grown under sub-optimal concentrations of conventional antibiotics will acquire a more negatively charged surface (as revealed by electrophoresis) which at the same time becomes less hydrophobic (as revealed by a hydrophobicity test), i.e. these bacteria with a surface structure which has been modified by antibiotics, will not attach or only weakly to any type of cells in our body, which contributes to the healing process. Our approach is still more efficient since it prevents bacteria from multiplying.

(2) A completely new method to make harmful bioparticles inactive is to encapsulate them by artificial gel antibodies which are further described below.

(3) It has recently been found by electrophoresis that all carbohydrates (i.e. also those on the surface of pathogenic bacteria) interact with water- soluble, aromatic compounds, for instance benzoic acids and naphtalene sulfonic acids; alkyl groups interact more weekly. The more benzene rings, the stronger is the interaction. Accordingly, an over-all hydrophilic substance with many benzene rings or alkyl chains will by multiple-point interactions form a strong bond to carbohydrates. Such a group of compounds is, accordingly, polyphenols. It is known that many people going abroad drink whisky which contains polyphenols to avoid tourist diarrhea (particularly earlier when the hygiene was not that high as nowadays). This habit could certainly also have another less serious back-ground, but it is yet very likely that the method is effective, since the polyphenols should, as pointed out above, react with the carbohydrates on the surface of the pathogenic (E. coli) bacteria and thus make them inactive.

Conventional antibiotics are designed to enter the bacterium and inhibit the nucleotide biosynthesis, or DNA replication, or RNA transcription, or protein synthesis of the bacterium without affecting these activities in the human cell. Therefore, a lot of many and very expensive animal experiments are required to test whether this requirement is fulfilled. These experiments often have the character of "trial and error" which increases the total cost so enormously that only one known company in the world has the courage to develop new, conventional antibiotics. In addition , a new antibiotics of the tradtional type will have a short life time because of the rapid development of resistence against antibiotics, which contributes to the above-mentioned well-known fact that the interest among companies to develop novel antibiotics is rudimentary.

It is thus obvious that a new type of antibiotics is required, which is not based on the generation of disturbances of the metabolism of the bacterium, since the bacterium quickly can change its metabolism by a Darwin evolution in such a way that a particular antibiotics is no longer active. The present application describes such a novel type of antibiotics, which also should become less expensive to develop: a hydrophobic entity which does not enter the bacterium (and cannot thus affect its metabolism), but reacts with its membrane. The bacterium thus cannot multiply, i.e. it is harmless to the human cell. Such entities are used which do not become attached or so weakly to the human cells that their metabolism is not negatively affected. It may also be so that the hydrophobic entity will not affect the metabolism of the human cell at all, even if it is strongly attached.

It has earlier been found that the more pathogenic a bacterium is, the higher is its surface hydrophobicity and the more it differs from the surface hydrophobicity of human cells, i.e. the hydrophobic polymers which are used will thus attach stronger to microorganisms than to human cells, or not at all. In this case the microorganisms become immobilized and loose its ability to multiply, whereas the human cells are not or only slightly affected; see below. (It is, of course, possible to employ other parameters than hydrophobicity to attach a polymer to the pathogen, but the principle should be the same). Observe that hydrophobic polymers (or particles) ate used, i.e. entities so large that they cannot penetrate the human cell wall and, therefore, they will not directly affect the metabolism of the human cell, or more likely not at all.

Interestingly, small molecules, such as benzoic acid and citric acid, are widely used as preservatives in marmelades and soft drinks, i.e. they prevent bacteria from multiplying. The reasons for their preserving properties are not known. Accordingly some of them should be useful as antibiotics, and particularly in a mixture at low concentrations of the separate preservatives in order to minimize possible side effects (although no such effects seem to be known).

Detailed description of the invention

It is intended throughout the present description that the expression "support matrix" embraces any matrix which is built up of an in water insoluble or/and swelling material, which may be a polymer, and large enough not to pass the cell membranes.

Examples thereof are polygalactanes (comprising polygalactose units), agar and agarose or derivatives thereof, laminarine, cellulose or derivatives thereof, cross-linked dextran or derivatives thereof, and starch or derivatives thereof. A polysaccharide such as agarose and cellulose may be regarded as thread-shaped molecules consisting of monomer units containing several hydroxyl groups and internal and external ether bonds (acetal bonds), which taken together give the polysaccharide affinity to water (it is said to be hydrophilic). Such polymers form in water swellable gels with hydroxyls as targets for substitution. It is also possible to use a polymeric backbone (preferably comprising polyethylene) covered with cellulose or similar material as a support matrix. The support matrix may further be present in particulate form. Many of the above supports can with advantage be used in cross-linked form.

It is intended throughout the present description that the expression "artificial antibodies" embraces any antibodies which are built up according to the method as set out in US 5,814,223 for chromatographic media. These antibodies are synthesized in such a way that cavities form in the gel, the shape of which is complementary to the shape of the harmful bioparticle (which must be present during the synthesis of the gel antibodies). This selectivity is strengthened by specific bonds, often hydrogen bonds and induced dipole-dipole interaction, between the "antigen" (= the harmful bioparticle) and the cavities in the gel antibody. Such artificial antibodies (which are gel antibodies), and manufacture thereof, are also described in Ivett Basckay et al, Electrophoresis 2006, 27, 4682-4687 (gel antibodies against bacteria), Anikό Takatsy et al, J. Sep. Sci. 2006, 29, 2802-2809 (gel antibodies against proteins) and Anikό Takatsy et al, Electrophoresis 2007, 28, 2345-2350 (gel antibodies against proteins). The artificial antibodies are gel particles with the size 0. 1 to 0.2 mm ( i.e. they are not proteins). Therefore they should in general be used as they are without binding to any matrix, such as cellulose or agarose. They are prepared by the molecular imprinting approach. They are probably more selective than are the conventional protein antibodies. These artificial granular gel antibodies can be synthesized to interact selectively with both proteins, viruses and bacteria.

The over-all selectivity of the artificial gel antibodies is extremely high, although some cross-reaction takes place, i.e. the artificial gel antibodies will recognize and encapsulate also bioparticles which somewhat differ in their chemical surface structure. This is an advantage, since also mutated bacteria (for instance those created by conventional antibiotics) and viruses will be encapsulated and, thus, made harmless (encapsulated bioparticles cannot multiply, see above). Further conventional vaccines must be injected prior to disease breaks out, while injection of artificial gel antibodies are effective both before and after the outbreak. This is obviously an advantage in comparison with current vaccines.

It is intended throughout the present description that the expression "carrier" embraces any carrier which is a pharmaceutically acceptable carrier and is suitable in a pharmaceutical composition. The pharmaceutical composition may be in formulations for oral, rectal, parenteral or other modes of administrations. The carrier may be in form of a solid, semi-solid or liquid diluent, or capsule. Said pharmaceutical preparations are a further object of the invention. Usually the amount of active compound is between 0.1-95% by weight of the preparation, between 0.2-20% by weight in preparations for parenteral use and between 1-50% by weight in preparations for oral administration. In the preparation of pharmaceutical formulations in form of dosage units for oral administration the carrier may be a solid, powdered carrier, such as lactose, saccharose, sorbitol, mannitol, starch, amyiopectin, cellulose derivates, gelatin or another suitable carrier. The mixture is then processed into granules or pressed into tablets. Granules and tablets may be coated with an enteric coating which protects the active compound from acid catalysed degradation as long as the dosage form remains in the stomach. The enteric coating is chosen among relevant pharmaceutically acceptable enteric -coating materials. To the coating various dyes may be added in order to distinguish among tablets or granules with different amounts of the active compound present. The carrier and the enteric coating must not interact with the active substance. Solutions for parenteral administrations may be prepared as solutions of the product as set out above according to the first aspect of the invention in pharmaceutically acceptable solvents, preferably at a concentration from 0.1 to 10% by weight. These solutions may also contain stabilizing agents and/or buffering agents and may be manufactured in different unit dose ampoules or vials. Solutions for parenteral administration may also be prepared as dry preparations to be reconstituted with a suitable solvent extemporaneously before use.

According to a further embodiment of the first aspect of the present invention there is provided a product wherein the hydrophobic entity is a saturated or unsaturated hydrocarbon chain with a chain length of from C₅ to C₂₅ or one or more aromatic groups i. e. an alkyl or alkylen with a chain length of from C₅ to C₂₅, preferably with a chain length of from C₈ to Ci₈, most preferred a saturated or unsaturated hydrocarbon chain with a chain length of from C₁₂ to C₁₈. The hydrocarbon chain may be included in a compound such as QUAB 342 (see below) or in QUAB 360 or QUAB 426 (which also comprise a positively charged group). AKD (provider Akzo Nobel) may also be used (with a lacton ring): R- CH=C - CH-R I I

According to a further embodiment of the first aspect of the present invention, there is provided a product wherein the positively charged entity is a positively charged group, preferably an amino group or ammonium group (by using an appropriate pK-of the amino group it may be changed e.g in abdomen, but not e.g. in blood). The ammonium group may be contained in a compound such as QUAB 342 (3-chloro-2-hydroxypropyl-dimethyl- dodecylammonium chloride) or in QUAB 360 and QUAB 426 (QUAB is a trade name of Degussa for solutions of the active substance 3-chloro-2-hydroxypropyl-dimethyl-alkyl- ammonium chloride). In said compound a methyl group within the quarternary ammonium group is substituted by a long-chain alkyl group (alkyl = dodecyl-, cocoalkyl-or stearyl-)). These compounds may be in the form of chlorohydrins. Instead of Cl-there may be a CCO- group (i. e. an epoxide group).

According to a further embodiment of the first aspect of the present invention there is provided a product wherein the support matrix comprises a polysaccharide, polygalactane, agar, agarose, laminarine, cellulose, crosslinked dextran, starch or a derivative thereof; or a mixture of two or more of said compounds; preferably said support matrix comprises cellulose.

According to a further embodiment of the first aspect of the present invention there is provided a product wherein the support matrix comprises a positively charged polymer, such as DEAE-dextran and chitosan. Chitosan has a positive charge and many properties which are of interest from a medical point of view. The product as mentioned in the first aspect of the invention may be manufactured as set out below (here cellulose is the support matrix):

1) Cellulose-OH +CI-C₁₈H₃₆-NH₂ (At a relatively high pH)

2) Elimination of Cl^"

3) CeIIuIoSe-O-C₁₈H₃₆-NH₂ (a product as mentioned in the first aspect of the invention)

In the third aspect of the present invention preferably air-borne and/or liquid- borne microorganisms, as well as viruses, preferably airborne (in pa rticular influenza viruses, SARS-virus) and/or liquid-borne viruses, and also allergens, the air-borne and/or liquid-borne microorganisms may be wound pathogens such as Staphylococcus aureus, Group A beta- haemolytic streptococci, urinary catheter-related pathogens such as Escherichia coli, eczema-related pathogens such as Candida albicans and various bacteria, and burn pathogens such as Pseudomonas aeruginosa. Moreover," new" pathogens prevalent particularly in the hospital setting are of interest, including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE)₁ Acinetobacter spp., multiresistant gramnegative intestinal bacteria, Stenotrophomonas maltophilia etc.

It should be noted and recalled that all microbes as well as viruses are negatively charged and most pathogenic microbes as well as viruses express strong or moderate cell surface hydrophobicity. The same principle may be used to trap air-borne and/or liquid-borne allergens. A further advantage with the present invention is the possibility of capturing liquid-borne microorganisms such as bacteria as well as viruses, which also preferably may be liquid-borne, efficiently even if there is a high concentration of salts in the liquid where the microorganisms such as bacteria as well as viruses reside. Thus said liquid may have a varying content of salts ranging from virtually zero (water) to liquids comprising high concentration of salts. Said liquid may further be a buffer. An increase of the salt concentration decreases the electrostatic interactions but increases the hydrophobic interactions i.e. at least one of these interactions is always active.

Preferred features of each aspect of the invention are as for each of the other aspects mutatis mutandis. The prior art documents mentioned herein are incorporated to the fullest extent permitted by law. The invention is further described in the following examples which do not limit the scope of the invention in any way.

Embodiments of the present invention are thus described in more detail with the aid of examples of embodiments, the only purpose of which is to illustrate the invention and are in no way intended to limit its extent.

Examples

The first medical trials should be very simple, cheap and as safe as possible and may be performed in the gastro-intestinal tract, nose and throat. The substances which are connected to different carriers appear not to be dangerous in such trials. We know that Helicobacter pylori is inactivated in test tube experiments by the method described herein. Therefore it is very likely that gastric ulcer can be cured by the method described herein. The composition according to the first aspect of the present invention may also be injected into the blood circulation.

Possibly the artifical antibodies, which are selective, may be most suitable in trials conducted to treat HIV as these artifical antibodies only react with the antigen (e.g. HIV), and not with any other particles or molecules. The artifical antibodies may also pick up a certain pathogen bacteria, without reacting with other bacteria or any other cells or any other particles or molecules as a whole.

When referring to two reference examples of interest to the present application, in these cases only very hydrophobic particles to adsorb and, thus, kill (inactivate) the pathogenic bioparticles (bacteria and viruses) were used.

(i) Rabbits were orally infected by enterotoxigenic E. coli bacteria to induce diarrhea. By feeding the rabbits with agarose beads, derivatized with palmitoyl groups, the diarrhea ceased (Torkel Wadstrδm et al, "A new principle for prevention of Diarrhea caused by Enterotoxigenic Escherichia CoIi (ETEC) Possessing Colonization factor Antigen (CFA), Scand. J. Infect Dis. 13:129-137, 1981) .

(ii) A horse infected by a virus recovered following administration with silica particles, derivatized with hydrophobic groups.

Various embodiments of the present invention have been described above but a person skilled in the art realizes further minor alterations, which would fall into the scope of the present invention. The breadth and scope of the present invention should not be limited by any of the above-described exemplary embodiments, but should be defined only in accordance with the following claims and their equivalents. For example, any of the above- noted compositions and/or methods can be combined with other known methods. Other aspects, advantages and modifications within the scope of the invention will be apparent to those skilled in the art to which the invention pertains.

Documents cited in the description: WO 2004110193 US 5,814,223

Ivett Basckay et al, "Universal method for synthesis of artificial gel antibodies by the imprinting approach combined with a unique electrophoresis technique for detection of minute structural differences of proteins, viruses and cells (bacteria). Ill: Gel antibodies against cells (bacteria)", Electrophoresis 2006, 27, 4682-4687 Anikό Takatsy et al, "Universal method for synthesis of artificial gel antibodies by the imprinting approach combined with a unique electrophoresis technique for detection of minute structural differences of proteins, viruses and cells (bacteria). Ia: Gel antibodies against proteins (transferrins)", J. Sep. Sci. 2006, 29, 2802-2809.

Anikό Takatsy et al, , "Universal method for synthesis of artificial gel antibodies by the imprinting approach combined with a unique electrophoresis technique for detection of minute structural differences of proteins, viruses and cells (bacteria). Ib: Gel antibodies against proteins (hemoglobins)", Electrophoresis 2007, 28, 2345-2350 and

Torkel Wadstrόm et al, "A new principle for prevention of Dihorrhea caused by Enterotoxigenic Escherichia CoIi (ETEC) Possessing Colonization factor Antigen (CFA), Scand. J. Infect Dis. 13:129-137, 1981

Claims

1. Pharmaceutical composition comprising a product for adsorption purposes, preferably in particulate form or polymeric form, most preferred for oral use or intravenous use, consisting of an in water insoluble or swelling support matrix wherein the support matrix is substituted with a hydrophobic entity which in turn is connected to a positively charged entity, other than said in water swelling or insoluble support matrix, and/or a product for adsorption purposes comprising a first support matrix connected to a hydrophobic entity and a second support matrix connected to a positively charged entity, and/or a product for adsorption purposes consisting of an in water insoluble or swelling support matrix wherein the support matrix is substituted with a hydrophobic entity and a positively charged entity, and/or one or more artificial antibodies, and/or a product for adsorption purposes consisting of an in water insoluble or swelling support matrix wherein the support matrix is substituted with a hydrophobic entity, and/or one or more preservatives, and optionally a carrier.

2. A pharmaceutical composition according to claim 1 , characterized in that the hydrophobic entity is a saturated or unsaturated hydrocarbon chain with a chain length of from C₅ to C₂₅ or one or more aromatic groups, an alkyl or alkylen with a chain length of from C₅ to C₂₅, preferably with a chain length of from C₈ to C₁₈, most preferred a saturated or unsaturated hydrocarbon chain with a chain length of from C₁₂ to C₁₈.

3. A pharmaceutical composition according to any of the preceding claims wherein the positively charged entity is a positively charged group, preferably an amino group or an ammonium group.

4. A pharmaceutical composition according to any of the preceding claims, wherein the support matrix comprises a polysaccharide, polygalactane, agar, agarose, laminarine, cellulose, crosslinked dextran, starch or a derivative thereof; or a mixture of two or more of said compounds; preferably said support matrix comprises cellulose.

5. A pharmaceutical composition according to any of the preceding claims, wherein the support matrix comprises a positively charged polymer, such as DEAE-dextran and chitosan.

6. Medical use of a product for adsorption purposes, preferably in particulate or polymeric form, consisting of an in water insoluble or swelling support matrix wherein the support matrix is substituted with a hydrophobic entity which in turn is connected to a positively charged entity, other than said in water swelling or insoluble support matrix, and/or a product for adsorption purposes comprising a first support matrix connected to a hydrophobic entity and a second support matrix connected to a positively charged entity, and/or a product for adsorption purposes consisting of an in water insoluble or swelling support matrix wherein the support matrix is substituted with a hydrophobic entity and a positively charged entity, and/or a product for adsorption purposes consisting of an in water insoluble or swelling support matrix wherein the support matrix is substituted with a hydrophobic entity, and/or one or more preservatives, and/or one or more artificial antibodies .

7. Use of a product for adsorption purposes, preferably in particulate or polymeric form, consisting of an in water insoluble or swelling support matrix wherein the support matrix is substituted with a hydrophobic entity which in turn is connected to a positively charged entity, other than said in water swelling or insoluble support matrix, and/or a product for adsorption purposes comprising a first support matrix connected to a hydrophobic entity and a second support matrix connected to a positively charged entity, and/or a product for adsorption purposes consisting of an in water insoluble or swelling support matrix wherein the support matrix is substituted with a hydrophobic entity and a positively charged entity, and/or a product for adsorption purposes consisting of an in water insoluble or swelling support matrix wherein the support matrix is substituted with a hydrophobic entity, and/or one or more preservatives, and/or one or more artificial antibodies, for the manufacturing of a medicament for treating pathogenic microbes, such as bacteria and viruses.

8. Therapeutic use of a product for adsorption purposes, preferably in particulate or polymeric form, consisting of an in water insoluble or swelling support matrix wherein the support matrix is substituted with a hydrophobic entity which in turn is connected to a positively charged entity, other than said in water swelling or insoluble support matrix, and/or a product for adsorption purposes comprising a first support matrix connected to a hydrophobic entity and a second support matrix connected to a positively charged entity, and/or a product for adsorption purposes consisting of an in water insoluble or swelling support matrix wherein the support matrix is substituted with a hydrophobic entity and a positively charged entity, and/or a product for adsorption purposes consisting of an in water insoluble or swelling support matrix wherein the support matrix is substituted with a hydrophobic entity, and/or one or more preservatives, and/or one or more artificial antibodies.