HK1096303A - Body care product containing porous silver particles - Google Patents

Description

Body care product containing porous silver particles

The present invention relates to a body care product and to the use thereof for the preparation of a medicament for the treatment of inflammation and/or infection.

WO 02/17984 a1 discloses an antibacterial material for deep implantation in bone or coating or preparing implants or deeply implantable medical devices. For this material, the particles formed from the antimicrobial metal are finely dispersed in a matrix material, which forms the matrix in the therapeutic state. The metal may be formed from one or more of the following components: ag. Au, Pt, Pd, Ir, Sn, Cu, Sb and Zn.

WO 00/78281 a1 discloses an antimicrobial body care product which exhibits an organic matrix part which is in contact with the skin and/or mucous membranes of humans or animals. This matrix comprises uniformly dispersed particles of metallic silver. Here, the size of the particles is between 1 and 50 nm. Particles of this size are referred to as nanoparticles. These particles are present in an amount on the portion of the surface that is in contact with the skin and/or mucosa that provides an antibacterially effective amount of the concentration but less than the cytotoxin. For example, the body care product may be an ointment or cream.

From Brumfield, G.Nature (2003), Vol.424, pages 246-248, it is known that these nanoparticles can be absorbed by animals. For example, the nanoparticles can penetrate through the lungs into the blood. The effect of nanoparticles on human health as they penetrate the body remains unclear. Thus, according to WO 00/78281 a1, the effect of the nanoparticles present in the silver-containing body care products on human health is also unclear.

DE 69321139T 2 discloses an antimicrobial composition containing inorganic particles coated with metallic silver. The particles may incorporate a polymer. They have a diameter of 0.01 to 100 μm, i.e.they may also be present in the form of nanoparticles. The object of DE 69321139T 2 is to provide antimicrobial granules which can be easily incorporated into a polymer matrix and which minimize interaction with the polymer. The particles have a protective layer of low porosity over the silver and are readily dispersed in the polymer. The protective layer is intended to prevent the metal from coming into too close contact with its surroundings.

DE 3886193T 2 discloses titanium-mica composition materials which are used as pigments for cosmetics and which have a coating comprising metallic, pulverulent silver. The object of DE 3886193T 2 is to provide materials suitable for dye or pigment use.

WO 00/78282A 1 discloses a silicone rubber compound containing metallic silver particles of 1-50 nm size. The silver particles are present in an amount to provide an antibacterially effective silver concentration on the surface of the compound, but less than the cytotoxin.

JP 61257908A discloses a cosmetic composition containing a powder coated with a metal powder such as silver. Here, the silver coating is obviously used only for the purpose of providing optical properties.

The object of the present invention was to provide a body-care product which has antibacterial activity and which does not exhibit the disadvantages of the body-care products disclosed in WO 00/78281 a1 in relation to nanoparticles. Furthermore, the use for the preparation of a medicament for the treatment of inflammation in a mammal or a human is described in detail.

The object of the invention is achieved by the features of claims 1 and 16. Suitable embodiments are characterized by the features of the subsequent claims 2 to 15 and 17 to 31.

The present invention provides a body care product comprising porous particles containing metallic silver, which are formed of a metal and which have an average particle diameter of 1 to 100 [ mu ] m.

The body care product is a product that can be brought into contact with human or animal skin and/or mucous membranes in order to obtain a cleaning, protective, therapeutic, curative, nursing, cosmetic or impact-reducing effect. For example, these products are typically presented on the skin-contacting surface and contain natural or synthetic polymeric materials. For example, these products may be any absorbent article such as feminine hygiene care articles, in particular sanitary napkins, panty liners or tampons, incontinence pads, diapers, baby training pants, medical bandages, plasters, non-woven materials, textiles, cellulose, toothbrushes or false nipples. The body care products can be prepared from or comprise natural products such as wool, viscose, cellulose and its derivatives or natural rubber. They may also be made of plastic or plastic containing particles of porous metallic silver. The plastic may be, for example: polyethylene and its derived copolymers, polypropylene and its prepared composite polymers, polyisobutylene, homopolymers and copolymers of polystyrene, acrylic-butadiene-styrene-terpolymers (ABS), synthetic rubbers, hard and soft polyvinyl chloride (PVC), Polytetrafluoroethylene (PTFE), Polychlorotrifluoroethylene (PCTFE) and other fluoropolymers, polyvinyl ethers, polyvinyl acetate, polyvinyl propionate, polyvinyl alcohol, copolymers of vinyl alcohol, polyvinyl acetals, polyethylene glycols, acrylic polymers, polymethyl methacrylate, polyacrylonitrile, polycyanoacrylates, polymethacrylimide-based polymers, polyacrylimides, polyvinylamines, polyamides including polyisophthaloyl isophthalamide, poly (p-phenyleneterephthalamide)), linear polyurethanes and polyesters including polyethylene terephthalate (PET), poly (isobutylene terephthalate), poly (ethylene terephthalate), poly (, Polybutylene terephthalate (PBT) and polytetramethylene terephthalate (PTMT), polycarbonates and their derived polymers, Polyoxymethylenes (POMs), polyethers, polyether ether ketones, polyether block amides, condensation resins such as phenolics and aminoplasts, crosslinked polyesters including polyester resins, epoxy resins, crosslinked polyurethanes, based on methyl methacrylate, polysiloxanes and other reactive resins with inorganic backbones.

The body care product may also be a preparation, in particular a medically active preparation, such as a cream, lotion, gel, cream, ointment, therapeutic ointment, powder, cosmetic product, skin-protective cream or ointment, disinfectant or anti-inflammatory agent, emulsion, soap, synthetic surfactant, bath additive, peeling preparation, facial lotion, dental care product, toothpaste, mouthwash, tooth-cleaning chewing gum, denture adhesive, shampoo, sunscreen, etc. These products generally comprise a carrier for a polymer or organic component that is a good substrate for the growth of many microorganisms. The growth of these microorganisms on these substrates can cause care or medical problems.

The particles may be present in the body care product in an amount such that a concentration of silver ions, which may be a microbiologically effective amount but less than a cytotoxin, is present where the body care product is in contact with the skin and/or mucous membranes.

Since the particles have a size of 1 to 100 μm, the particles and particles consisting of metal present in the body care product according to the invention do not cause the potential risk of nanoparticles. According to the use of the body care product, the particles are not able to penetrate deeper layers of the skin into the tissue or blood vessels and also not able to overcome the blood brain barrier when the product is used. As a result, the antimicrobial effect alone is limited to the skin surface. This thus avoids causing allergic reactions and undesirable toxic effects. However, it has been found that the silver ions released from the particles due to the porosity of the particles are sufficient to be able to provide a body care product having suitable antibacterial and anti-inflammatory activity. An anti-inflammatory effect can be achieved when the concentration of particles in the body care product is higher than desired for the antibacterial effect only. In particular, silver ions act on the surface of the skin or mucous membranes that come into contact with the body care product and do not have a negative effect on the underlying tissue. As a result, the particles are more skin-compatible than nanoparticles due to the size of the particles that prevent penetration into the skin. The particles are less cell destructive and more biocompatible than nanoparticles containing metallic silver. As a result, the body care products according to the invention are suitable, in particular for patients who have to be concerned with body care and body hygiene for a long time. For example, these patients may be individuals, such as diabetic patients who have a weakened immune system and/or an increased risk of contracting skin infections. Since it has been found that the body care product according to the invention often gives additional use of superfluous antibiotics, it may also prevent the development of antibacterial agents.

The body care product according to the invention has an antibacterial effect and, where appropriate, also an anti-inflammatory effect. In addition, the product does not require any preservative other than the granules because of the antibacterial effect of metallic silver. In particular, it may be in the form of a medical recovery or care ointment, cream or gel. Such formulations may be used medically as a replacement for corticoid-containing formulations due to anti-inflammatory effects. When the product is used as a hand cream, ointment or gel, the antibacterial effect also protects against the transfer of pathogens, such as by hand grasping, and prevents the penetration of organisms when there is a small wound on the hand. In addition to these, because preservatives can be saved, incompatible reactions such as allergy are particularly less likely to occur.

The particles preferably have an average internal porosity of at least 65%, in particular from 65 to 95%. Internal porosity may be understood as the percentage of the volume of the particles that is not filled with metal. The average internal porosity of the particles can be determined using the following method:

1. the particles are implanted in the plastic material and,

2. the ultra-fine fraction of the implanted particles is prepared,

3. the particles were photographed (TEM) using a Transmission Electron Microscope (TEM),

4. the percentage of the internal area of each particle that is not filled with metal relative to the total area of this particle is determined in most TEM photographs, and

5. the average of the multiple percentages determined using this method was calculated.

In such a context, method step 4 of computer-aided image analysis by TEM images can be influenced. In addition to the internal porosity of the porous material,the total porosity of the particles can also be determined. Thus, the beating density of the granular powder is first determined. The beating density is the mass per unit volume of the powder, which is layered as densely as possible by beating. The beating density may be determined according to DINISO 3953. The value determined from this relationship was calculated as a percentage of the density of the metal forming particles, in this case a silver density of 10.49g/cm³And subtracted from 100%. The value calculated by this method constitutes the total porosity of the particle. As regards those particles which are included in the body care product according to the invention, it may be from 85 to 95%, in particular from 90 to 95%, more preferably from 93 to 95%.

It is particularly advantageous for the particles to have an average internal porosity of from 65 to 90%, in particular from 70 to 85%, preferably from 75 to 85%, or from 85 to 95%, more preferably from 90 to 95%. The choice of porosity may be used to account for the amount of silver ions released from the particles over a particular period of time. If a high porosity is chosen, this will therefore release a lot of silver ions, which means that the full antibacterial and anti-inflammatory effect is achieved by using low amounts of silver in the body care product. On the other hand, the total duration of silver ion release is reduced by increasing the porosity and simultaneously reducing the amount of silver. It is therefore advantageous to rely on the application for a porosity of 70-85% or 85-95%.

Preferably, the particles are present as sintered agglomerates of metallic primary particles. The sintered compact may be formed of primary particles having an average particle diameter of 10 to 200nm, preferably 15 to 80 nm. Primary particles of this size allow for the proper release of silver ions and can be easily produced. In each case, the average distance between the outermost primary particles on the surface of the agglomerates is preferably 20 to 200nm, more preferably 100 to 200 nm. The primary particles can be identified by electron microscopy based on their outer shape and size. The spherical structure of the particles can be seen, for example, as shown in figure 1. The primary particles are connected to each other by a sintered plug.

The porous particles preferably have a sponge-like structure. The large surface thus makes it possible to release a suitable amount of silver ions with a suitable antibacterial, anti-inflammatory effect.

The particles preferably have an average outer diameter of 2 to 20 μm, more preferably 2 to 5 μm. The specific surface area of the particles can be 2-10 m²A specific volume of 3 to 6m²A ratio of 3.5 to 4.5 m/g²(ii) in terms of/g. For example, the specific surface area can be determined by N using the BET method₂The volume was determined by adsorption. The BET method, which is a method named Brunauer, Emmett and Teller for determining the surface of a solid object, such as a powder, and the appropriate pore size distribution, is based on the gas, vapor, initially absorbed as a monolayer on a released solid object with measurable heat of adsorption. For example, it is possible to measure the volume of nitrogen gas adsorbed by the adsorbent at-196 ℃ depending on the pressure applied.

The particles preferably consist of at least 99% w/w (weight percent), more preferably 99.9% w/w metallic silver. Such high levels of silver do not cause significant cytotoxic effects due to other metal ions, particularly copper ions. Unless otherwise indicated, the metal content percentages given herein and below refer to the given metal weight as a percentage of the total weight of the particle. Expressed herein as a weight percentage (% w/w). It is particularly advantageous if the particles comprise less than 5ppm of potassium, sodium or chlorine impurities. High levels of impurities in silver can cause undesirable side effects.

It is particularly advantageous if the particles comprise up to 0.5% w/w metallic copper and/or 0.5% w/w metallic zinc. These two substances also have an antibacterial effect and are mutually supporting, and have a common effect with silver. This is due, inter alia, to the fact that, with their common antibacterial effect, they exhibit different specificities for microorganisms. In addition, zinc shows excellent wound healing and anti-inflammatory effects when combined with silver, and copper is also suitable. The reason for this may be that silver and copper are suitably present, able to prevent the growth of microorganisms that interfere with wound healing and such growth is not inhibited by the zinc ions themselves. In addition, copper may promote the formation of alloys comprising silver and zinc. In general, a body care product comprising zinc and/or copper in addition to silver has a superior wound healing and anti-inflammatory effect than a body care product comprising only one metal. Preferred particles are formed from a silver-zinc alloy or a silver-zinc-copper alloy.

The body care product preferably does not comprise any preservatives other than the particles. It has been found that metal ions exhibit a preservative effect. It is therefore possible to dispense with preservatives. This also avoids the adverse effects, particularly allergic reactions, associated with the use of preservatives such as formaldehyde.

The particles may be present as a carrier material consisting of silicone oil, mineral oil, glycerol or a conventional pharmaceutically-known ointment component. For the preparation of a body care product according to the invention, the agglomerates can be prepared by thermally evaporating the agglomerate-forming metal and then depositing the metal vapor on the metal filter. The agglomerates may be present in a carrier material that can be incorporated into the body care product. For example, the carrier material can be silicone oil, mineral oil, glycerol or the usual pharmaceutically known ointment constituents.

Furthermore, the present invention relates to the use of porous particles comprising metallic silver, which particles are formed of a metal and which have an average particle size of 1 to 100 μm, for the preparation of a medicament for the treatment of inflammation and/or infection in a mammal or a human. Commonly used agents for treating inflammation in mammals or humans often include mixtures containing anti-inflammatory and antibacterial active compounds. The antibacterially active compounds are useful in the prevention or control of infection, particularly with Staphylococcus aureus. The antibacterially active compounds are generally antibiotics. Alternatively, where the anti-inflammatory active compound is administered topically, the antibiotic may also be administered systemically. However, because of the risks involved, particularly the development of antibiotic resistance over long-term use, the use of anti-drug substances should be minimized. Examples of anti-inflammatory active compounds used earlier are corticoids such as cortisone, which may show many side effects. The essential advantage of the medicament prepared according to the invention is that the granules exhibit an anti-inflammatory effect and an antibacterial effect. The use of antibiotics can be reduced and the side effects of corticosteroids or other anti-inflammatory active compounds can be avoided.

The treatment preferably takes place topically, i.e. for example applied to the skin or a wound. The medicament may be an ointment, cream or gel. Further advantageous embodiments of the use of the body care product according to the invention result from the above point of view.

The invention is explained in more detail in the following with the aid of exemplary embodiments. The attached drawings are as follows:

FIG. 1 shows a scanning electron micrograph of a silver agglomerate, and

FIG. 2 shows a matrix plot of the chronological course of bacterial growth in contact with different pasty body care products, measured as Optical Density (OD) of the culture medium.

FIG. 1 shows a scanning electron micrograph of a silver agglomerate. In this case, the silver agglomerates essentially comprise spherical primary particles having an average particle size of about 60 nm. The primary particles are essentially connected to each other in the manner of sintering necks. They form a highly porous structure. The size of the silver agglomerates represented here is about 10 μm.

The results shown in fig. 2 were measured using the method disclosed in DE 19751581 a 1. This method is also described by Bechert, Thorsten et al, Nature Medicine (2000), Vol 6, No 8, pages 1053-1056. The disclosures of the two aforementioned documents are incorporated herein by reference. The body-care products according to the invention were tested in the form of a finished paste, in each case using the material as carrier and then carrying out the tests described above. The experiment was tested in detail as follows:

different cream samples were first produced. An amount of 11 mg of cream was applied to each carrier. A200. mu.l aliquot of the solution containing Staphylococcus epidermidis was placed in each well of the microtiter plate. In each case the vehicle and cream were placed in each well together and incubated at 37 ℃ for 1 hour. The vector was then removed and washed three times with physiological buffer solution. The vector was then placed in microtiter plates containing 200. mu.l minimal medium in each case. The carrier was cultured at 37 ℃ for 24 hours. The carrier is then removed and discarded. Mu.l of complete medium (Trypcase-soya, bioMerieux, No.69280, Marcy l' Etoil, France) was added to each well on the microtiter plate. The turbidity of the solution was then measured at 30 minute intervals over 48 hours. During this time, the solution was maintained at 37 ℃. Turbidity was measured at 578nm light wavelength using a suitable reader. Turbidity indicates bacteria that have been released from the carrier surface into the environment.

Certus Handels GmbH, Spinnrad  "Cremaba Plus HT", from Norderstedt 22848, Germany, was used to produce a matrix paste of paste-like samples. The matrix paste is an emulsion matrix having the following components: water, caprylic/capric triglyceride, pentadienyleneglycol, hydrogenated lecithin, shea butter, glycerol, squalane, and ceramide 3. The following additional components were incorporated into the matrix paste:

a silicone oil containing 0.65% w/w silver; in which the silver is present in the form of particles having an average diameter of 10 nm; the silver is referred to below as "nanodispersed silver"; or

Sintered lumps of metallic silver in powdered form, having an average porosity of 80% and an average grain size of 5 μm; the silver described below is referred to as "agglomerate silver".

A cream containing 0.01% w/w of agglomerated silver and a cream containing 0.5% w/w of agglomerated silver were prepared. In addition, a cream containing 0.05% w/w of agglomerated silver was prepared, in this case with agglomerated silver consisting of an alloy containing 99.5% w/w silver, 0.49% w/w zinc and 0.01% w/w copper. In addition, a cream containing 1.5% w/w of agglomerated silver was prepared, in this case with agglomerated silver consisting of an alloy containing 99.5% w/w silver, 0.49% w/w zinc and 0.01% w/w copper.

To prepare the creams, the starting materials were mixed in each case in a 50 ml glass beaker and heated in a water bath at 75 ℃ for 20 minutes; they were then dispersed for 5 minutes using an Ultraturrax (Janke and Kunkel, T25 power, stator diameter 25 mm, rotor diameter 17 mm). The cream was then cooled and mixed thoroughly again.

FIG. 2 shows each region of the x-y curve, with time plotted on the x-axis and optical density plotted on the y-axis. The results of the experiments were determined as described in columns 1 to 8 of FIG. 2, and the following creams were used in parallel experiments to assay the rows A to H corresponding to A to H:

column 1, rows A-H: cream without adding any silver

Column 2, rows A-H: cream containing 0.1% w/w of agglomerated silver

Column 3, rows A-H: cream containing 0.5% w/w of agglomerated silver

Column 4, rows A-H: cream comprising 1.5% w/w agglomerate silver consisting of 99.5% w/w silver, 0.49% w/w zinc and 0.01% w/w copper

Column 5, rows A-H: cream containing 0.1% w/w of agglomerated silver

Column 6, rows A-H: cream comprising 0.05% w/w of agglomerated silver consisting of 99.5% w/w silver, 0.49% w/w zinc and 0.01% w/w copper

Column 7, row a: positive regulation

Column 7, row B: negative regulation

Column 7, row C: blank value

Column 8, rows A-H: sterile regulation

Polymers containing metallic silver are used in the case of positive conditioning. The values indicate that the bacteria used are sensitive to and can be killed by silver. The same polymer was used in the case of negative regulation, but did not contain any silver. Blank values are values obtained by measuring on a blank microtiter plate and are subtracted when analyzing all measurements. In each case, no staphylococcus epidermidis was added, only the medium was used in the case of sterility regulation in order to demonstrate that the bacterial growth did not originate from the medium.

The results of the experiments are summarized below:

specifying the sample	Starting OD [ h ]]Total value of	Starting OD [ h ]]Net worth of	Effect
				1A-H emulsifiable paste without adding any silver	5.2	0	No antibacterial property
2A-H cream containing 0.1% w/w of agglomerated silver	18.4	13.2	High antibacterial property
				3A-H cream containing 0.5% w/w of agglomerated silver	32.2	27.0	High antibacterial property
4A-H cream comprising 1.5% w/w agglomerate silver consisting of 99.5% w/w silver, 0.49% w/w zinc and 0.01% w/w copper	37.9	32.7	High antibacterial property
				5A-H cream containing 0.1% w/w of agglomerated silver	35.3	30.1	High antibacterial property
6A-H cream comprising 0.05% w/w agglomerated silver consisting of 99.5% w/w silver, 0.49% w/w zinc and 0.01% w/w copper	Extreme limit	＞42.8	Sterilizing property
				7A/B Positive/negative Regulation	Limit/9.2	-	Good taste
8A-H aseptic adjustment	Extreme limit	-	Good taste
				Blank value of 7C		-	Good taste

"Total OD h onset" means that the time measured in hours increases the Optical Density (OD) exponentially to 0.2. The "net starting OD h" is the value of the "total starting OD h" in each case minus the "total starting OD h" measured for the cream without silver addition. When the assays of the parallel experiments were completed, the average value for each case was given. "antibacterial property" means an effect when the growth of bacteria is delayed, and "bactericidal property" means that 100% of the bacteria are killed so that no bacterial growth is observed.

The experimental results show that the sintered silver, such as nanodispersed silver, has high antibacterial activity. Nanodispersed silver is also active at lower silver concentrations than sintered silver. However, a high antibacterial effect can still be achieved when using sintered silver. In creams containing zinc and copper in addition to silver, both the effect of agglomerated silver and the effect of nanodispersed silver are increased.

Claims (31)

1. A body care product comprising porous particles of metallic silver, present in a form of metal and having an average diameter of 1 to 100 μm.

2. A body care product according to claim 1 wherein the particles have an average internal porosity of at least 65%, particularly 65 to 95%, preferably 65 to 90%, more preferably 70 to 85%, most preferably 75 to 85%, or preferably 85 to 95%, more preferably 90 to 95%.

3. Body care product according to claim 1 or 2, wherein the particles are present as sintered agglomerates of metallic primary particles.

4. Body care product according to claim 3, wherein the primary particles have an average diameter of 10 to 200nm, preferably 15 to 80 nm.

5. Body care product according to claim 3 or 4, wherein the average distance between the outermost primary particles in each case at the surface of the agglomerates is in the range from 20 to 200nm, more preferably from 100 to 200 nm.

6. Body care product according to any one of the preceding claims, wherein the particles have a sponge-like structure.

7. Body care product according to any one of the preceding claims, wherein the particles have an average outer diameter of from 2 to 20 μm, preferably from 2 to 5 μm.

8. Body care product according to any one of the preceding claims, wherein the particles have a specific surface area of from 2 to 10m²A specific volume of 3 to 6m²A ratio of 3.5 to 4.5 m/g²/g。

9. Body care product according to any one of the preceding claims, wherein the particles contain at least 99% w/w metallic silver, preferably 99.9% w/w.

10. The body care product according to any one of the preceding claims wherein said particles contain less than 5ppm of potassium, sodium or chlorine impurities.

11. Body care product according to any one of the preceding claims, wherein the particles contain 0.5% w/w metallic zinc and/or 0.5% w/w metallic copper.

12. The body care product according to any one of the preceding claims, wherein the particles are formed of a silver-zinc alloy or a silver-zinc-copper alloy.

13. The body care product according to any one of the preceding claims, wherein said body care product is free of any preservatives other than said particles.

14. Body care product according to any one of the preceding claims, wherein the particles are present in a carrier material consisting of silicone oil, mineral oil, glycerin or ointment ingredients.

15. Body care product according to any one of the preceding claims, wherein the body care product is a formulation, in particular the formulation is a medically active formulation, such as a cream, lotion, gel, cream, ointment, therapeutic ointment, powder, cosmetic product, skin protection cream or ointment, disinfectant, emulsion, soap, synthetic surfactant, bath additive, peeling preparation, facial wash, dental care product, toothpaste, mouthwash, dental cleansing gum, denture adhesive, shampoo, sunscreen or absorbent article, such as a feminine hygiene article, in particular a sanitary napkin, panty liner or tampon, incontinence liner, diaper, baby training pants, medical bandage, plaster, non-woven material, textile, cellulose, toothbrush or false nipple.

16. Use of porous particles containing metallic silver, said particles being formed of a metal and having an average diameter of 1 to 100 μm, for the preparation of a medicament for the treatment of inflammation and/or infection in a mammal or a human.

17. Use according to claim 16, wherein the particles have an average internal porosity of at least 65%, in particular 65 to 95%, preferably 65 to 90%, more preferably 70 to 85%, most preferably 75 to 85%, or preferably 85 to 95%, in particular 90 to 95%.

18. Use according to claim 16 or 17, wherein the particles are present as sintered agglomerates of metallic primary particles.

19. Use according to claim 18, wherein the primary particles have an average diameter of 10 to 200nm, preferably 16 to 80 nm.

20. Use according to claim 18 or 19, wherein the average distance between the outermost primary particles in each case at the surface of the agglomerates is in the range from 20 to 200nm, more preferably from 100 to 200 nm.

21. Use according to any one of claims 16 to 20, wherein the particles have a sponge-like structure.

22. Use according to any one of claims 16 to 21, wherein the particles have an average outer diameter of from 2 to 20 μm, preferably from 2 to 5 μm.

23. Use according to any one of claims 16 to 22, wherein the particles have a specific surface area of from 2 to 10m²A specific volume of 3 to 6m²A ratio of 3.5 to 4.5 m/g²/g。

24. Use according to any one of claims 16 to 23, wherein the particles contain at least 99% w/w metallic silver, preferably 99.9% w/w.

25. The use of any one of claims 16 to 24, wherein the particles contain less than 5ppm of potassium, sodium or chlorine impurities.

26. Use according to any one of claims 16 to 25, wherein the particles contain 0.5% w/w metallic zinc and/or 0.5% w/w metallic copper.

27. The use as claimed in any one of claims 16 to 26, wherein the particles are formed from a silver-zinc alloy or a silver-zinc-copper alloy.

28. The use of any one of claims 16 to 27, wherein the medicament is free of any preservative other than the particles.

29. The use of any one of claims 16 to 28, wherein the treatment is topical treatment.

30. The use of any one of claims 16 to 29, wherein the medicament is an ointment, cream or gel.

31. Use according to any one of claims 16 to 30, wherein in the medicament the particles are present in a carrier material consisting of silicone oil, mineral oil, glycerol or ointment components.