EP-4739117-A1 - ANTIMICROBIAL COMPOSITIONS

Abstract

Powder compositions are described which comprise enzyme that is able to convert a substrate to release hydrogen peroxide, substrate for the enzyme, and polymer. The composition comprises a first set of particles interspersed with a second set of particles. The first set of particles comprises the enzyme and the polymer, but substantially none of the substrate. The second set of particles comprises the substrate, but substantially none of the enzyme.

Inventors

• HALL, THOMAS

Assignees

• Matoke Holdings Limited

Dates

Publication Date

20260513

Application Date

20240705

Claims (20)

1. 1 . A powder composition comprising enzyme that is able to convert a substrate to release hydrogen peroxide; substrate for the enzyme; and polymer, the composition comprising a first set of particles interspersed with a second set of particles, the first set of particles comprising the enzyme and the polymer, but substantially none of the substrate, and the second set of particles comprising the substrate but substantially none of the enzyme.
2. 2. The composition according to claim 1 , wherein the first set of particles comprise the enzyme suspended in, or coated with, the polymer.
3. 3. The composition according to any preceding claim, in which the total amount of the polymer is greater than 75%, by weight, of the composition.
4. 4. The composition according to any preceding claim, in which the substrate is less than 5%, by weight, of the composition.
5. 5. The composition according to any preceding claim, wherein the total amount of sugar is less than 5%, by weight, of the composition.
6. 6. The composition according to any preceding claim, in which the polymer comprises polyvinyl alcohol.
7. 7. The composition according to any preceding claim, in which the polymer comprises polyethylene glycol.
8. 8. The composition according to any preceding claim, comprising less than 0.5%, by weight, superabsorbent polymer, preferably substantially no superabsorbent polymer.
9. 9. The composition according to any preceding claim comprising substantially no peroxidase.
10. 10. The composition according to any preceding claim comprising salt, preferably wherein the salt comprises a buffer.
11. 11 . The composition according to any preceding claim, wherein the enzyme comprises glucose oxidase and the substrate comprises glucose.
12. 12. The composition according to any preceding claim which is sterile.
13. 13. The composition according to any preceding clause comprising subst
14. 14. A wound dressing which comprises a dressing material for dressing a wound, and a composition according to any preceding claim.
15. 15. A composition according to any of claims 1 to 13, for use as a medicament.
16. 16. A composition according to any of clauses 1 to 13, for use in prevention, treatment or amelioration of a microbial infection.
17. 17. A method of preparing a powder composition, the powder composition optionally as defined in any of claims 1 to 13, the method comprising: forming a solution comprising polymer, and enzyme that is able to convert a substrate to release hydrogen peroxide; drying the solution to form a dried mixture comprising the enzyme and the polymer; and adding substrate for the enzyme in powder form, to the dried mixture.
18. 18. The method according to claim 17, wherein the solution is an aqueous solution.
19. 19. The method according to claim 17 or claim 18, wherein the solution comprises a salt, preferably a buffer
20. 20. The method according to claim 19, wherein the solution has an ionic strength of 5 to 100 mM, preferably 10 to 75 mM, more preferably 25 to 50 mM.

Description

Antimicrobial Compositions This invention relates to compositions, such as powder compositions, for generating hydrogen peroxide, and their use in treating infections and wounds. Honey has been used for treatment of microbial infections since ancient times. In recent years there has been a resurgence of interest in the therapeutic efficacy of honey, particularly in the area of wound healing. Clinical trials have shown that honey is an effective broad-spectrum antimicrobial agent which is effective against common wound-infecting organisms, such as Pseudomonas aeruginosa, Staphylococcus aureus, Candida albicans and Escherichia coli, and is effective against antibiotic-resistant strains of bacteria. As a natural product, honey also offers an attractive alternative to drug-based treatments. Many different types of honey have antimicrobial activity. This activity is attributed largely to osmolarity, pH, hydrogen peroxide production and the presence of phytochemical components. The applicant has appreciated that the antimicrobial effects of honey can be greatly enhanced and controlled by adding glucose oxidase to honey, and that compositions comprising honey and added glucose oxidase are applicable in the treatment of a number of infections, and notably in the treatment of infections caused by biofilms (see WO 2015/166197, WO 2016/083798 and WO 2016/124926). However, because honey is a natural product, its composition can vary greatly depending on its source. For example, the difference in antimicrobial potency among honeys can be more than one hundred-fold, depending on the geographical, seasonal and botanical source of the honey, as well as the harvesting, processing and storage conditions. Consequently, the antimicrobial efficacy may also vary depending on the type of honey used. Furthermore, honey may also contain other components, such as allergens e.g. trace amounts of pollen, which may cause adverse reactions when applied to certain subjects and make it unsuitable for certain pharmaceutical applications. There is also considerable variability in physical characteristics such as viscosity and colour. Honey is sticky and can be difficult to apply and remove from a patient. Honey may also require processing such that it is in a suitable form for application to subjects, which can add cost and complexity to the production process. Such processing may include creaming or pasteurisation. Consequently, there is a desire to provide improved compositions which provide enhanced antimicrobial efficacy compared to honey, and which also overcome some of honey’s disadvantages. There is also a desire to provide compositions with improved stability. The applicant has formulated synthetic liquid and gel compositions which ma improvements over honey-based compositions, such as those disclosed in WO 2020/193993 and WO 2021/186165. However, although liquids and gels may be advantageous for certain applications, they may not be optimal for other applications. For example, powders may be more advantageous in certain circumstances. For instance, powders may be more readily applied to dressing materials to form antimicrobial dressings. In certain circumstances, powders could be applied directly to a wound. Superabsorbent powder compositions comprising superabsorbent polymer are disclosed in WO 2019/077335. However, it is desired to provide powders that are not necessarily superabsorbent, and which have improved stability. For example, it is desired to provide dry compositions, such as powders, which maintain the ability to generate hydrogen peroxide at effective levels and which maintain their consistency, minimising clumping or aggregation, after being stored for extended periods of time. Maintaining stability of powder compositions that are able to generate hydrogen peroxide is particularly challenging. The applicant has found that powder compositions comprising glucose oxidase and glucose exhibit a significant decrease in the ability to generate hydrogen peroxide even after storage for 60 days in a 99.9% nitrogen atmosphere. This suggests that maintaining stability may be more complex than simply minimising exposure to atmospheric water and oxygen, to prevent background generation of peroxide, and the degeneration of the enzyme. The applicant has, however, formulated compositions with improved stability. In a broad sense, the invention concerns compositions which include enzyme that is able to convert a substrate to release hydrogen peroxide. Preferably, such compositions are able to generate hydrogen peroxide on addition of water. Such compositions may also include substrate for the enzyme. The invention also concerns methods of making such compositions that are able to generate hydrogen peroxide. For example, this may include combining enzyme that is able to convert a substrate to release hydrogen peroxide and substrate for the enzyme. Preferably, the composition is a dry composition. According to the invention there is pr