WOUND TREATMENT DRESSING, METHOD OF OBTAINING AND USES THEREOF

Abstract

The present disclosure relates to a wound treatment dressing in which an absorbent layer comprises an odour-inhibiting mixture; wherein the odour-inhibiting mixture comprises coffee grounds. More particularly, a wound treatment dressing is provided for the absorption of odours in wounds, including pressure ulcers, leg ulcers, cancerous wounds, diabetic foot ulcers, burns, traumatic or surgical wounds, which comprises an odour-inhibiting mixture with coffee grounds.

Claims

1. A wound treatment dressing comprising: an absorbent layer comprising an odour-inhibiting mixture, wherein the odour-inhibiting mixture comprises coffee grounds, wherein the granulometry of the ground coffee grounds varies between 3-5000 μm, wherein the odour-inhibiting mixture comprises 10-40% (W/V.sub.inhibiting mixture) of coffee grounds, and wherein the odour-inhibiting mixture comprises an adhesion agent, a dispersant, a binding agent or a buffer solution, or mixtures thereof.

2. The dressing according to claim 1, wherein the granulometry of the ground coffee grounds varies between 4-4000 μm.

3. The dressing according to claim 1, wherein the odour-inhibiting mixture comprises 15-30% (w/V.sub.inhibiting mixture) of coffee grounds.

4. The dressing according to claim 1, wherein the absorbent layer comprises between 0.05 to 5 g of coffee grounds per cm.sup.2 of absorbent layer.

5. The dressing according to claim 1, wherein the coffee grounds are dried and/or ground.

6. The dressing according to claim 1, wherein the dressing further comprises an outer layer comprising a textile substrate, which serves as a support for the absorbent layer carrying the inhibiting mixture.

7. The dressing according to claim 1, wherein the absorbent layer further comprises superabsorbent polymers.

8. (canceled)

9. The dressing according to claim 1, wherein the dressing comprises 0.5-5% (V/V.sub.inhibiting mixture) of bonding agent.

10. The dressing according to claim 1, wherein the adhesion agent is selected from a list consisting of: a highly active matrix based on anionic, cationic, non-ionic, amphoteric agents, and combinations thereof.

11. The dressing according to claim 1, wherein the binding agent is selected from a list consisting of: chitosan, phosphate buffer solution, gelatin, pectin, cellulose, cellulose derivatives, glucomannan, acrylic emulsions, styrene-butadiene emulsions, styrene-acrylic emulsions, polyurethane-based dispersions, and combinations thereof.

12. The dressing according to claim 1, wherein the dispersant is selected from a list consisting of: polyester, siloxane, polyphosphates, polyacrylates, and combinations thereof.

13. The dressing according to claim 1, wherein the absorbent layer further includes an active ingredient, a moisturizer, a disinfectant, an anesthetic agent or combinations thereof.

14. The dressing according to claim 1, wherein the absorbent layer is coated through a Meyer bar and/or film applicator.

15. (canceled)

16. The dressing according to claim 1, wherein the textile substrate is a natural fiber, a synthetic fiber or combinations thereof.

17. The dressing according to claim 1, wherein the pH range of the buffer solution is between 6 and 10.

18. The dressing according to claim 1, wherein the textile substrate comprises cotton, polyester, non-woven fabric, or combinations thereof.

19. A method for absorbing the odour of a wound in a subject, comprising administering to the subject a transdermal dressing wherein the transdermal dressing comprises: an absorbent layer comprising an odour-inhibiting mixture; wherein the odour-inhibiting mixture comprises coffee grounds, wherein the granulometry of the ground coffee grounds varies between 3-5000 μm, wherein the odour-inhibiting mixture comprises 10-40% (w/V.sub.inhibiting mixture) of coffee grounds, and wherein the odour-inhibiting mixture comprises an adhesion agent, a dispersant, a binding agent or a buffer solution, or mixtures thereof.

20. (canceled)

21. A method for producing a dressing according to claim 1, comprising the following steps: preparing the odour-inhibiting mixture with coffee grounds; placing the odour-inhibiting mixture in the absorbent layer; applying the absorbent layer on a textile substrate; drying in the oven, preferably infrared (IR) at 100° C., the substrate with the composition; and pressing or laminating the structure in order to obtain the dressing, preferably pressing at 110° C. with a pressure of 6 bar for 1 minute.

22. The method for producing the dressing according to claim 21, wherein the coffee grounds are ground at 400 rpm for 30 minutes; whenever the inhibiting mixture is prepared and the textile is further functionalized.

23. The method for producing the dressing according to claim 21, wherein the odour-inhibiting mixture comprises a binding agent and wherein preparation of the binding agent comprises the following steps: preparing a mixture of water or a phosphate buffer solution; adding chitosan and acetic acid under mechanical/magnetic stirring until the chitosan is well dissolved and the solution is homogeneous; adding the coffee grounds to the chitosan solution; mixing well using a mechanical stirrer; and adding the silane and keeping stirring until the mixture is well homogeneous.

Description

BRIEF DESCRIPTION OF THE FIGURES

[0059] For an easier understanding, figures are herein attached, which represent preferable embodiments which are not intended to limit the object of the present description.

[0060] FIG. 1—Illustration of an embodiment of the results of the reduction capacity of isovaleric acid (IVA) by the different layers of the commercial dressings Carboflex® and Actisorb®.

[0061] FIG. 2—Illustration of a preferred embodiment of the techniques used in the coating: (a) there is the film applicator, (b) the knife coating and (c) the Meyer bar is present.

[0062] FIG. 3—Illustration of an embodiment of an intersection edge of two fitted square sides of the half cube.

[0063] FIG. 4—Illustration of an embodiment of the results of the IVA reduction capacity by TNT PES functionalized with the various compounds analysed and the respective formulation of the present embodiment.

[0064] FIG. 5—Illustration of an embodiment of the results obtained from IVA reduction capacity by the 100% CO fabric functionalized with the various compounds analysed and the respective controls under study.

[0065] FIG. 6—Illustration of an embodiment of results obtained from IVA reduction capacity by the 100% CO and CO/PES fabric functionalized with different amounts of grounds and respective controls under study.

[0066] FIG. 7—Illustration of an embodiment of the results obtained from the IVA reduction capacity by the CO/PES fabric functionalized on one side and on both sides with the formulation of ground and unground coffee grounds and respective controls.

[0067] FIG. 8—Illustration of an embodiment of the IVA reduction capacity by the 100% CO fabric functionalized with the formulation of grounds at different concentrations of silane and respective controls.

[0068] FIG. 9—Illustration of an embodiment of the IVA reduction capacity by the CO/PES fabric functionalized with the formulation of grounds at different concentrations of silane and respective controls.

[0069] FIG. 10—Illustration of an embodiment of the IVA reduction capacity by the prototypes of dressings developed with the outside in TNT, inner layer 100% CO or CO/PES with formulation and the respective complete dressings.

[0070] FIG. 11—Illustration of an embodiment of the IVA reduction capacity by the prototypes of complete dressings developed with the outside in TNT and/or CO/PES and respective controls, on different days and by different operators.

[0071] FIG. 12—Illustration of an embodiment of the IVA reduction capacity over 24 hours, by the Actisorb® dressing and the two dressings developed.

[0072] FIG. 13—Illustration of an embodiment of the granulometries of ground coffee grounds.

[0073] FIG. 14—Illustration of an embodiment of the diameter of the wire used in the rod of the Meyer bar.

DETAILED DESCRIPTION

[0074] The present disclosure relates to a wound treatment dressing, in particular for the absorption of odours in wounds, including pressure ulcers, leg ulcers, cancerous wounds, diabetic foot ulcers, burns, traumatic or surgical wounds, which comprises an odour-inhibiting mixture with coffee grounds.

[0075] The present disclosure describes a wound treatment dressing comprising: an absorbent layer comprising an odour-inhibiting mixture; wherein the odour-inhibiting mixture comprises coffee grounds. In an embodiment, the granulometry of ground coffee grounds varies between 3-5000 μm; preferably between 4-4000 μm; more preferably 5-3000 μm and the coffee grounds are dried and/or ground. The dressing further comprises an outer layer comprising a textile substrate, which serves as a support for the absorbent layer; an absorbent layer comprising a textile substrate, which serves as a support for the inhibiting mixture. The odour-inhibiting mixture comprises an adhesion agent, where the odour-inhibiting mixture comprises 0.5-5% (V/V.sub.inhibiting mixture) of the adhesion agent; and 20-25% (W/V.sub.inhibiting mixture) of coffee grounds. In an embodiment, the odour-inhibiting mixture further comprises a dispersant, a binding agent and a buffer solution.

[0076] The present disclosure describes a wound treatment dressing comprising: an absorbent layer comprising an odour-inhibiting mixture; wherein the odour-inhibiting mixture comprises coffee grounds.

[0077] In an embodiment, the wound treatment dressing of the present disclosure comprises a granulometry of ground coffee grounds that ranges from 5-5000 μm and are dried/ground.

[0078] In an embodiment, the dressing further comprises: an absorbent layer comprising a textile substrate, which serves as a support for the inhibiting mixture. It also describes a method for producing the dressing that comprises the following steps: preparing the odour-inhibiting mixture with coffee grounds; placing the odour-inhibiting mixture in the absorbent layer; applying the absorbent layer on a textile substrate; drying in the oven, preferably infrared at 100° C., the substrate with the composition; pressing or laminating the structure in order to obtain a dressing, preferably pressing at 110° C. with a pressure of 6 bar for 1 minute.

[0079] In order to compare the performance of the present disclosure’ dressings, two types of commercial dressings were analysed, both indicated for the treatment of exudates and the management of chronic wound odour. These commercial dressings feature a layer of activated carbon as an odour-absorbing substrate. One of the main objectives of this disclosure consisted in the replacement of activated carbon by coffee grounds, since these show a high absorption/neutralization area and, at the same time, allowing to add value to a by-product of the coffee industry.

[0080] In an embodiment, the commercial dressings analysed were Carboflex® and Actisorb Silver 220®, marketed by the international companies Convatec® and Systagenix®, respectively.

[0081] In an embodiment, in order to evaluate the odour retention capacity of the commercial dressings studied, the gas chromatography technique with flame ionization detection (Gas Chromatography—Flame Ionization Detector, GC-FID) was used according to a procedure adapted from ISO 17299-3:2014—Determination of deodorant properties—Part 3: Gas chromatography method. The gas chromatograph (GC) with flame ionization detector used corresponds to the 2010 Plus model of the Shimadzu brand. The capillary column is from the brand Teknokroma, model Meta.X5, nonpolar, 50 m long, with an internal diameter of 0.20 mm and a film thickness of 0.33 μm. The chromatograph has a “split/splitless” type injector, set to a split ratio of 1:5. The results were obtained using the GC Solution version 2.4 software, specific from Shimadzu.

[0082] Commercial dressings, despite being considered efficient in terms of absorbing chronic wound exudates, after 24 hours in contact with the wounds have the problem of releasing the unpleasant odour of the exudate into the surrounding environment. Therefore, the IVA retention capacity of the different layers of the commercial dressings under analysis was evaluated, as shown in FIG. 1. In the scope of this disclosure, only IVA was used, since it is one of the odorous compounds frequently found in the beds of patients with chronic wounds who, in turn, have bacterial colonization or infection.

[0083] In an embodiment, as shown in FIG. 1, it appears that commercial dressings show very similar results, in terms of the reduction of this odorous marker, by the different layers. Between layers it is also observed that there are no significant differences in the percentage of reduction in IVA, for both commercial dressings.

[0084] In an embodiment, taking into account that the minimum percentage of IVA reduction, referred to by the standard, for a fabric (dressing) to be considered deodorant regarding this odour, is 85%, it can be said that both dressings present this property. However, after each test, the textile layers were smelled and it was found that the outer layers of both dressings absorbed and retained the odour of the analysed odorous compound. This situation may mean that this layer acts as a barrier in the interaction of the compound with the inner layer (of activated carbon), promoting a lesser reduction of the odours released from the exudate of chronic wounds, when the dressing is complete. Regarding the inner layer, it was found that it had no smell after the test, which indicates that this layer of activated carbon has the capacity to neutralize the odour. The higher percentage of IVA reduction for the inner layer (≈98%), followed by the complete dressing (≈94%) and, in turn, the outer layer (≈90%) proves what has been stated above. In general, it is concluded that, in terms of the capacity to reduce odours, the two commercial dressings behave similarly.

[0085] In an embodiment, for the incorporation of coffee grounds into the textile substrate, the use of the Meyer bar, with a thickness of 100 μm, was used. This technique made it possible to easily obtain a uniform coating with the desired thickness, as shown in FIG. 2. In this way, the Meyer bar was used in the incorporation of formulations with coffee grounds, in the different textile substrates. After the formulation was applied to the textile support, the coating was subjected to drying in an IR oven at 100° C. Finally, the samples were pressed at 110° C., with a pressure of 6 bar for 1 minute.

[0086] In an embodiment, the textile material with coffee grounds was developed using the textile substrates of 100% (V/V) CO, 63% (V/V) CO/37% (V/V) PES and TNT PES.

[0087] In an embodiment, several formulations were evaluated to define the most suitable one either in terms of spreading, or in terms of the amount of grounds and their effect on the capacity to reduce odours.

[0088] In an embodiment, the addition of thickeners such as cellosize (hydroxymethylcellulose) and CMC (carboxymethylcellulose) to the coffee grounds was assessed, however the amounts tested made it difficult to spread the formulation.

[0089] In an embodiment, the presence of a binder such as chitosan, glucomannan (konjac fiber) and impranil was also assessed. Glucomannan, although promoting a good texture to the formulation, acts as a prebiotic agent stimulating the growth and/or activity of certain bacteria. In this sense, it is not at all advisable in medical terms, as the formulation may be in contact with a wound. Impranil is an acrylic polymer resin that creates a film on the textile support, preventing to some extent the absorption of odours by the coffee grounds. Regarding chitosan, its addition makes the formulation with a viscosity suitable for spreading and still provides antimicrobial properties, important conditions considering the application purpose. However, the solution of chitosan in acetic acid with the coffee grounds is not sufficient for the formulation to have a good adhesion and uniformity on the textile substrate.

[0090] In an embodiment, taking into account these problems, the addition of a dispersant, such as TEGO WET 240 (highly active compound based on siloxane), and an adhesion agent, such as silane, was evaluated. The dispersant mentioned, despite improving the texture of the formulation with the coffee grounds and its spreading, is a copolymer of polyester siloxane. As such, it is a very reactive compound, so it has a high odour reduction capacity. In this sense, its presence masks the effect of the grounds, which is not intended with the present disclosure. Regarding silane, its presence has made the adhesion of grounds to the textile more efficient. Although at concentrations between 5-10% (V/V) it has the same effect as TEGO, in terms of the capacity to reduce odours, at low concentrations (0.1-3% (V/V)) this is not found, not influencing the effect of coffee grounds.

[0091] In an embodiment, in terms of the capacity to reduce odours, grinding or not grinding did not show significant differences. However, the uniformity of the dispersion of the formulation applied to the textile improves considerably when using ground grounds. Therefore, it was decided to grind the coffee grounds in a ball mill at 400 rpm, for 30 minutes, whenever the textile was functionalized.

[0092] In an embodiment, the odour-inhibiting mixture with better results comprises 20-25% w/V.sub.total ground coffee grounds (SCG) in a 1% (w/V) solution of chitosan (Cs) in acetic acid (CH.sub.3COOH 1% (V/V)) and 0.5% (V/V) silane. Due to the acidity of this formulation with a pH≈4, it was decided to bring the pH of the solution to 7, taking into account the possible contact with the skin and/or exudate from wounds. Thus, the amount of acetic acid (CH.sub.3COOH) used was reduced to only 0.25% (V/V), using the phosphate buffer solution having pH≈7.4 in complementary manner.

[0093] In an embodiment, for the development of this embodiment, the inner layer of activated carbon of the commercial dressings was replaced by a coating with coffee grounds. In this sense, the present embodiment follows a structure similar to the dressings already existing on the market, being comprised by an inner layer and an outer layer.

[0094] In an embodiment, FIG. 3 shows how to make an embodiment of the dressings of the present embodiment, using a thermally adhesive tape for their closure.

[0095] In an embodiment, through the analysis of FIG. 4, it is possible to verify that both chitosan and acetic acid promote a small increase in the capacity of intrinsic reduction of IVA by TNT PES, although this is not significant. In contrast, 5% (V/V) of TEGO (dispersant) impregnated in the fabric promotes a considerable increase, which indicates that this compound masks the effect of coffee grounds when added together. The same occurs with 5% (V/V) and 10% (V/V) silane, although 5% (V/V) silane shows a lesser effect, which in a smaller percentage may be useful for binding the grounds to the textile and not masking the reduction capacity of the grounds themselves. These two compounds together provide a high IVA reduction capacity, taking into account their individual behaviors. The reduction capacity of the control fabric (everything but the grounds) and the fabric with the formulation had already been analysed and, in this case, it is present only for comparison.

[0096] In an embodiment, the results in FIG. 5 suggest that the effect of both compounds, TEGO (dispersant) and silane, is the same on the different substrates analysed. It is further noted that when adding TEGO to the fabric with chitosan and grounds (SCG), the percentage of IVA reduction considerably increases. Thus, it is confirmed that TEGO masks the effect of grounds, as its addition immediately promotes a high IVA reduction capacity. Regarding silane, it was found that in the range of 1-10% (V/V), together with the other compounds, its IVA reduction effect is practically the same and quite high, which means that the formulation would already be saturated in terms of odour reduction capacity with the addition of TEGO (5% (V/V).

[0097] In an embodiment of the present embodiment, it was decided to apply a formulation with only coffee grounds in a 1% (w/V) solution of chitosan in acetic acid, in 100% (w/w) CO and 63% (w/w) CO/37% (w/w) PES fabrics. In order to compensate for the removal of dispersant and silane in the formulation, it was decided to increase the amount of coffee grounds to 30% w/V.sub.total.

[0098] In an embodiment, the results of the chromatographic analysis, in terms of the odour reduction capacity of these samples and the respective controls without any type of coating, are shown in FIG. 6. As can be seen, for the substrate 100% (w/w) CO, there was no considerable increase when incorporating a greater amount of coffee grounds, so it was decided to continue with 25% w/V.sub.total of coffee grounds.

[0099] In an embodiment, for the CO/PES blend fabric, a behavior similar to 100% (w/w) CO fabric is observed, as can be seen in FIG. 7. However, the intrinsic reduction capacity of the controls, both with one and with two sides of chitosan, is less than in relation to the 100% (w/w) CO fabric. This result is advantageous, since it makes the effect of grounds more noticeable.

[0100] In an embodiment, as shown in FIG. 8 and FIG. 9, it appears that silane, in the concentrations tested and for both fabrics, does not have such a marked effect in terms of IVA reduction as in the concentrations previously tested. In addition to reaching a value close to that mentioned in the standard for the reduction of this marker, with these concentrations, an excellent formulation uniformity for spreading over the textile substrate is also obtained. Among the tested concentrations, and taking into account the values obtained for each one, it was decided to proceed with the use of 0.5% (V/V) of silane in future formulations. This is because, regarding the formulation of 0.1 and 1% (V/V) of silane, it reaches a value close to each other and ideal in relation to the standard criterion; and in comparison with the that of 3% it also reaches a close reduction value. In addition, the use of a lower concentration makes the formulation more beneficial for possible direct contact with the skin.

[0101] In an embodiment, FIG. 10 shows the results obtained for the dressing developed with the outer layer of TNT and the inner layer of 100% CO or CO/PES. It is possible to verify that, in dressings developed in comparison with the commercial ones, the outer layer has a IVA reduction capacity lower than the inner layer, allowing it to also act in the case of the complete dressing. Both TNT PES with 100% (w/w) CO as well as functionalized CO/PES show significant results in reducing this marker, taking into account the criterion defined in the standard, despite the latter being relatively impaired when complete.

[0102] In an embodiment, after each test, the wound dressings of the present embodiment were smelled and it was found that these neutralized/softened the odour of the odorous compound analysed. The same was not seen with the commercial dressings, so these prototypes showed the potential to overcome this problem.

[0103] In an embodiment, another way of making the dressings with the coffee grounds covered the application of them, loose, inside a kind of bag, which was later covered with an outer layer, using the same combination of fabrics. In the same study, it was also possible to evaluate the performance of this inner layer, with the loose grounds, individually, for direct application on chronic wounds. The amount of loose grounds added was 5 grams in little bags with approximately 50 cm.sup.2 of area.

[0104] In an embodiment, after analysing various parameters in terms of the form and quantity of grounds, the components of the formulation, the fabrics to be used and the most appropriate functionalization technique, the remaining studies followed with only 2 of the developed dressing prototypes. Namely, dressings with the outer layer in CO/PES coupled with the inner layer 100% (w/w) CO with formulation and the outer layer TNT with the inner layer 100% (w/w) CO coated with the formulation under study. The dressing with the outer layer in 100% (w/w) CO and the inner layer of CO/PES coated with the formulation was discarded from the following tests, considering that in terms of medical application it would not be so appropriate.

[0105] In an embodiment, FIG. 11 shows that there is consistency in the results obtained, inasmuch as these tests were performed 3 months apart and by different operators. In addition, the preparation of the formulations and the incorporation into the textile substrate 100% CO was also carried out on different days. Therefore, it can be said that the method of incorporating coffee grounds into the textile, the preparation of the dressings and their capacity in terms of the percentage of odour reduction is stable and controlled, not varying significantly.

[0106] Another problem of the art was that the commercial dressings, after some time of use, didn't have the capacity to neutralize the bad odour released by exudates of chronic wounds. In this sense, it was decided to evaluate this parameter using two different tests.

[0107] In an embodiment, the first trial consisted of assessing the odour retention capacity of the dressings (Actisorb® and the other 2 developed), over a period of 24 hours, allowing to monitor their effectiveness. To this end, 85 μl of IVA were injected in an Erlenmeyer flask, in each dressing, simulating the amount of exudate a leg pressure ulcer releases every half hour [L. F. B. Giraldo, “Extraction and characterization of polysaccharides and phenolic compounds from spent coffee grounds and their incorporation into edible films/coatings for food applications”, 2016]. The values were obtained after two hours, consecutive with each injection, until reaching 24 hours of contact with the dressings.

[0108] In an embodiment, the results shown in FIG. 12 show that the developed dressings exhibit a behaviour similar to the commercial dressing, in terms of odour reduction, during the 24 h of simulation. It should be noted that the dressing exterior in TNT and with the interior of 100% (w/w) CO with formulation has a more linear trend, over time and that after 24 hours the reduction capacity exceeds that of the commercial dressing.

[0109] In an embodiment, the odour of the dressings was qualitatively assessed throughout the test—characterized as a weak, medium, or strong odour, in order to determine their neutralization capacity (Table 1). In summary, it was noticed that the exterior dressing in TNT and with the interior of 100% CO with formulation only started to present a strong odour of IVA after 24 h, while the other two already released a strong odour to the surrounding air after 7 h.

TABLE-US-00001 TABLE 1 Qualifying evaluation of the IVA odour in the 24 h test, both for the commercial dressing and for the two developed prototypes. Dressings Qualification of IVA odour Actisorb ® Strong odour from 7 h Exterior TNT + Interior 100% CO with Strong odour after 24 h formulation Exterior CO/PES + Interior 100% CO with Strong odour from 7 h formulation
From the obtained results, it appears that the developed prototypes have an absorption capacity similar to the Actisorb® commercial dressing, despite being slightly lower. Regarding the Carboflex® commercial dressing, the absorption capacity of the developed dressings is much lower. This result can be explained by the fact that this dressing consists of 4 layers, allowing to absorb a greater amount of solution, compared to the developed prototypes. Anyway, as the developed dressings are structurally similar to Actisorb®, it can be said that in terms of absorption capacity the developed prototypes show satisfactory results. In general terms, dressings with greater absorption capacity are those that have the outside in TNT and an inner layer with grounds in formulation or loose.

[0110] In the present embodiment, FIG. 14 shows a Meyer bar as a technology for applying coatings, similar to a film applicator.

In this coating process, the formulation is deposited on the substrate and is displaced by means of a dosing rod wrapped in wire (Meyer bar). The Meyer bar allows the desired amount of coating to remain on the substrate and the amount is determined by the diameter of the wire used in the rod, in this case a wire with a diameter of 100 μm was used.

[0111] In an embodiment, the wound treatment dressings described in the present disclosure were sterilized by gamma radiation in the Unidade Tecnológica de Radioesterilização of the Instituto Superior Técnico with different doses of radiation (5, 15 and 25 kGy). The evaluation of the microbial load before and after sterilization was carried out at the Centro Tecnológico CITEVE—Tecnologia Têxtil (reports attached).

TABLE-US-00002 TABLE 2 Results of the microbiological control of the dressings of the present disclosure by the Portuguese Pharmacopoeia 2.6.12 Total No. of viable aerobic Bacteria, Fungi, germs (CFU/g) (CFU/g) (CFU/g) 1.sup.st test Without 2166 1770 396 sterilization 2.sup.nd test Without 1632 452 1180 sterilization  5 KGy 611 608 3.33 15 KGy 85 73.4 11.3 25 KGy 16 8.95 6.69

[0112] The term “comprises” or “comprising” when used herein is intended to indicate the presence of stated features, elements, integers, steps, and components, but not to preclude the presence or addition of one or more other features, elements, integers, steps and components, or groups thereof.

[0113] The embodiments described are combinable with each other. The present invention is not, of course, in any way restricted to the embodiments described in this document and a person with average knowledge in the art will be able to foresee many possibilities for modifying it and replacing technical features with equivalent ones, depending on the requirements of each situation, as defined in the appended claims.

[0114] The following claims define further embodiments of the present description.