EP1817044A1

EP1817044A1 - Composition comprising a polysaccharide with bacteria blocking action

Info

Publication number: EP1817044A1
Application number: EP05813977A
Authority: EP
Inventors: Alexander James Hanbury Duggan
Original assignee: Passion for Life Healthcare Ltd
Current assignee: Passion for Life Healthcare Ltd
Priority date: 2004-11-29
Filing date: 2005-11-29
Publication date: 2007-08-15
Also published as: WO2006056801A1; GB0426068D0

Abstract

A composition of an isotonic or hypertonic formulation or a powder for the preparation thereof is described comprising an active ingredient which is effective in blocking harmful bacteria and is selected from extracts of plant or animal origin and/ or derivatives thereof comprising a combination of polysaccharides comprising 60-100 % of D-mannose, 40-0 % of D-glucose and 0-10 % of other monosaccharides. An active ingredient which is effective in blocking harmful bacteria for use in a spray composition or douche so as to drench the surface tissue of a recipient; use of a composition in blocking adhesion of harmful bacteria to host tissues; and use of a composition in the manufacture of a medicament with this effect are also described.

Description

COMPOSITION COMPRISING A POLYSACCHARIDE WITH BACTERIA BLOCKING ACTION

The present invention relates to a composition for the preparation of an isotonic or hypertonic formulation comprising an active ingredient, a process for the preparation thereof and the use thereof for delivery to the ear, nose or eye of a human or animal.

Sea water isotonic sprays are known as hygiene prevention products, in particular sprays for the ear to disperse earwax and nasal douches for general nasal hygiene. Such sprays comprise no active therapeutically ingredients.

We have now found that such sprays may leave residual water, in particular in the ear where residual water is in the presence of fatty compounds present in wax at body temperature. This is perfect breeding ground for bacteria. Accordingly the use of such hygiene prevention products may lead to bacterial infection and inflammation.

Sprays exist incorporating antibiotics to combat bacterial infection, however these have the usual disadvantages associated with antibiotics e.g. are not recommended for prolonged use, are associated with side effects and can lead to immunity of bacteria and subsequent ineffectiveness of the composition.

There is therefore a need to provide hygienically safe products which avoid the disadvantages associated with antibiotics.

Examples of prior art sprays of both the above types are listed in the table below. product delivery manufacturer main added Action of added system ingredient/s ingredients ingredients

Physiomer Spray Goemar, France isotonic none N/A seawater

Sterimar Spray Lab Fumouze, 31.82ml / none N/A

(original) France 100ml of seawater

Sterimar Spray Lab Fumouze, 31.82ml / monohydrated manganese helps defend manganese France 100ml of manganese the organism against seawater salts allergens

Sterimar Spray Lab Fumouze, 31.82ml / pentahydrated Copper helps defend the copper France 100ml of copper salts organism against seawater infectious diseases

Sterimar Spray Lab Fumouze, 31.82ml / pentahydrated sulfur helps regenerate

Sulfur France 100ml of sodium cells that are affected by seawater thiosulfate recurring infections

Unimer spray & Lab. Die- 30% seawater none N/A vials pharmex, Switz. + 70% purified water

ProRhinel spray & Novartis, Switz. water polysorbate 80 antiseptic and vials + benzodo- fluidifying agents decinium

Bromure bebisol vials Lab. Phar- purified water sodium when added to water mygiene, France chloride (0.09%), makes it a physiological solution.

Propoline Spray LTEV, France purified water propolis Possible actions

+ sterilized extract include: antibacterial, seawater by antifungal, antiviral, micro filtration antioxidant, anticarcmogenic, antithrombotic, immunomodulatory

Humer 150 Spray Urgo, France Sterile none N/A physiological seawater

NasoMar Spray ????, Spain Seawater - no further info on this product

Triomer Spray Vifor, France Seawater - no further info on this product

Lyomer Spray Gifrer, France Sterile none N/A physiological seawater

Sinomarin spray & Lab Belobab, Natural none N/A vials France hypertonic seawater

Proceane Spray ????, France Isotonic none N/A

Spray seawater

Ocean solution

Proceane vials ????, France hypertonic none Note: Hypertonic

Hypertonic seawater seawater solution acts solution like a natural decongestant

Proceane vials ????, France Isotonic none N/A isotonic seawater solution

Hyvernyl Spray ????, Spain Hypertonic seawater solution - no further info on this product

Libenar spray & ???, Italy Physiological sodium when added to water vials solution of chloride (0.09%), makes it a purified water physiological solution. (not seawater)

Terme di spray Tabiano, Italy Spring water sodium when added to water Tabiano bicarbonate (0.09%), makes it a chloride physiological solution,

RJtiino- Spray Weleda Physiological aloe vera contains Aloe Vera gel doron saline solution in an isotonic salt solution. This means that the salt content of the solution is adjusted to match the body's fluids, so the solution is well tolerated by the mucous membranes

Poli Bimbi Spray ???, Italy Physiological liposome a spherical particle of solution fat suspended in a liquid medium. They may be used to carry drugs or other substances to cells or tissues

Acqua di vials ???, Italy spring water sulfur sulfur helps regenerates Sirmione cells that are affected by recurring infections

Neo baby vials ???, Italy Sterile physiological solution

Mustella vials water sodium when added to water

Pueri- chloride (0.09%), makes it a coltura physiological solution. Fidia nasal Mini Fidia purified water Hyaff, Care sprays Glycerin

Physio- vials Gifrer, France Physological sodium when added to water logica and isotonic chloride (0.09%), makes it a serum physiological solution. In this case isotonic,

Marplus spray Germany seawater dexpanthenol claimed to be pre-cursor of coenzyme A. Usually administered intraven¬ ously or intramusculary but can also be applied topically to the skin to stimulate healing of of various dermatologic lesions such as burns, infected wounds, eczema etc.

Tetesept (2 Spray Merz, Germany isotonic none N/A variants) seawater

Tetesept Spray Merz, Germany isotonic Zinc + echinacea is said to cure seawater echinacea cold and boost immunity + Zinc enriched products can promote fast healing

Tonimer Spray 111, Italy Isotonic none N/A seawater solution

Otrisalin Spray 111, Greece purified water sodium when added to water chloride (0.09%), makes it a physiological solution.

Vitaprolis Spray 111, france sterilised propolis Possible actions: seawater extract antibacterial, antifungal, antiviral, antioxidant, anticarcinogenic, antithrombotic, immunomodulatory We have now found that a certain class of active ingredients which are useful in combating bacteria by a bacterial blocking action are free from side effects and immunity. Moreover we have found that such products are ideally suited to a preventitive hygiene use.

Accordingly in the broadest aspect of the invention there is provided a composition of an isotonic or hypertonic formulation or a powder for the preparation thereof, comprising an active ingredient which is effective in blocking harmful bacteria, which composition may be used for the manufacture of a medicament which is effective in blocking adhesion of harmful bacteria to host tissues, the composition comprising an isotonic or hypertonic formulation or a powder for the preparation thereof including an active bacteria blocking ingredient selected from extracts of plant or animal origin and/ or derivatives thereof comprising a combination of polysaccharides comprising 60-100% of D-mannose, 40-0% of D-glucose and 0- 10% of other monosaccharides.

The isotonic or hypertonic formulation of the composition of the invention may be saline or desalinated and in one alternative is preferably a sea water or a desalinated fluid. Such formulations have known benefits in cleansing ears, nose and eyes with minimal disruption to the mucosa. In another alternative, in complete or partial substitution for sodium chloride, (or like electrolyte), an identified osmo-protectant (this is, a species known to mitigate the effect of osmosis between calls and the outside world) may be used, for example being trimethy glycine.

It is important to distinguish between antibiotic compositions that have antibacterial effect and bacteria blocking compositions. By reference to PCTYNL02/00868, the contents of which are incorporated by reference, we emphasise the role of bacteria blocking active ingredients. An active ingredient effective in blocking harmful bacteria is effective in blocking adhesion of such bacteria to host tissues. Active ingredients are known which are effective in preventing adhesion of harmful bacteria to host tissues, and in particular extracts of plant or animal origin, which term includes derivatives, compounds and mixtures of such extracts. Such extracts/ derivatives comprise polysaccharides derivable from the plant or animal and mixtures thereof. In particular they comprise a combination of polysaccharides comprising 60-100% of D-mannose, 40-0% of D- glucose and 0-10% of other monosaccharides.

Such active ingredients are in particular selected from extracts and/ or derivatives of aloe, in particular aloe vera and derivatives thereof.

Suitably a bacteria blocking active ingredient is negatively charged.

Suitably a bacteria blocking active ingredient extract is known from PCT/NL02/00868 (WO03/055918). That is to say, ascribed therein the active ingredient comprises negatively charged polysaccharides derivable from Aloe vera in a mixture 60-100% D-mannose, 40-0% D-glucose and 0-10% other monosaccharides and with an average molecular weight higher than 50 kD, for example about 100-300 kD. Preferably the mixture comprises 70-90% D-mannose, 30-10% D-glucose and 0-10% other monosaccharides. Preferably the mixture comprises D-mannose and D-glucose in a ratio of a range of about 5 to 20.

The composition may be delivered in any known manner and is preferably delivered as a spray, douche or equivalent which has the effect of drenching the surface tissue of a recipient. Preferably the composition is for delivery to the ear, nose or eyes of a human, non-human mammal or animal host. Suitably the composition of the invention is effective in administering to combat ear, nasal or eye sanitary hygiene conditions such as the build up of earwax, nasal mucus, cleansing of the eye and the like. It is a particular advantage that the composition of the invention may prevent inflammation and bacterial infections such as conjuctivitis or by bacteria such as MRSA (Methicillin Resistant Staphylococcus Aureus) and the like.

Examples of infections of the eye, ear, nose and throat which can be prevented and treated by anti adhesive polysaccharides of the present invention include those caused by:

Staphylococcus epidermis which plays an important role in the pathogenesis of some forms of endophthamitis occurring after cataract surgery

Moraxella bovis as the source of infectious bovine keratoconjunctivitis Staphylococcus aureus which adheres to the skin and mucous tissues

- bacteria involved in Otitis media and nasopharyngal infections such as Haemophilus influenza, Streptococcus penumoniae and Moraxella catarrhalis the oral cavity, wherein the dental plaque biofilm plays a pivotal role in the progression of dental diseases and polysaccharides are of great importance in the ecology of the dental biofilm, caused by

- bacteria involved in caries such as Streptoccoccus sobrinus as acariogenic strain, Streptocossus mutans, Streptococcus salivarius, Streptococcus gordonii and Actinomyces viscosus, Actinobacillus actinomycetecomitans

- periodontopathogenic bacteria such as Porphyromonas gingivalis and Streptococcus salivarius, Streptococcus oralis, Fusobacterium nucleatum and Prevotella intermedia

- All oral spirochetes which are classified in the genus Treponema, such as denticola, pectinovorum, socranskii and vincentii,

- Mycoplasma salivarium

- microorganisms involved in nasal polyposis

- microorganisms involved in Sinusitis The composition may include additional active ingredients, for example effective in combating snoring or apnoea dry eyes, irritated or tired eyes, decongestion, hay fever, allergy or tinnitus. The composition may include any suitable additional ingredients such as excipients, stabilisers, carriers, fillers and the like. Preferably the composition includes a humectant for example pentylene glycol. Conveniently, the composition includes up to 10 Wt % humectant where present, for example 1 — 5 Wt %.

Suitably in the composition of the invention the bacteria blocking active ingredient is present in any effective blocking amount, preferably in the range 1 - 20 Wt % and for example 2 - 10 Wt %.

The composition may be suitable for delivery by any known effective means and is preferably suitable for delivery by a spray dispenser, including a nasal, eye or eye spray dispenser, by pipette, as a wash, such as an eye wash or ear wash or a wash for nasal inhalation and the like. Suitable spray dispensers are known in the art and include pump spray dispensers comprising a reservoir fluidly connected to spray delivery means which are adapted to draw, aerosolise and deliver a controlled dose from the reservoir to a subject in use. Preferably a dispenser for delivery to the ear has a barrier to prevent overinsertion. Preferably a spray dispenser for dispensing to the ear comprises a dispersement nozzle suitable to provide a disperse jet to avoid ear drum damage.

Preferably the composition of the invention is provided as a solution, liquid, gel, ointment, suspension or the like or powder form to mix with fluid.

In a further aspect of the invention there is provided an active ingredient as hereinbefore defined which is effective in blocking harmful bacteria for use in a spray composition as hereinbefore defined and/ or in the manufacture of a medicament as hereinbefore defined.

In a further aspect of the invention there is provided a method of blocking adhesion of harmful bacteria to host tissues of a human, non-human mammal or animal host comprising applying an isotonic or hypertonic formulation including an active bacteria blocking ingredient selected from extracts of plant or animal origin and/ or derivatives thereof comprising a combination of polysaccharides comprising 60- 100% of D-mannose, 40-0% of D-glucose and 0-10% of other monosaccharides.

Preferably the method comprises applying the isotonic or hypertonic formulation to the ear, nose or eyes of the host.

Preferably the method comprises drenching the surface tissue of a recipient by delivering the composition as a spray or as a douche.

The method is in particular a method for the prevention and/ or treatment of inflammation and bacterial infections, including those caused by:

Staphylococcus epidermis; Moraxella bovis as the source of infectious bovine keratoconjunctivitis;

Staphylococcus aureus, including MRSA, which adheres to the skin and mucous tissues; bacteria involved in Otitis media and nasopharyngal comprising Haemophilus influenza, Streptococcus penumoniae and Moraxella catarrhalis ; bacteria involved in caries such as Streptoccoccus sobrinus as acariogenic strain,

Streptocossus mutans, Streptococcus salivarius, Streptococcus gordonii and

Actinomyces viscosus, Actinobacillus actinomycetecomitans; periodontopathogenic bacteria comprising Porphyromonas gingivalis and Streptococcus salivarius, Streptococcus oralis, Fusobacterium nucleatum and Prevotella intermedia; all oral spirochetes which are classified in the genus Treponema, comprising denticola, pectinovorum, socranskii and vincentii; Mycoplasma salivarium; microorganisms involved in nasal polyposis; and microorganisms involved in Sinusitis.

Other preferred features of the method will be understood by analogy with the foregoing description of the composition and its use.

The invention is now illustrated in a non-limiting manner with respect the following examples.

Composition 1 - Isotonic Nasal/ Aural spray

Purified Water (Solvent)

Betaine (Osmo-protectant isotonic solute)

Polysaccharide Constituent Pentylene Glycol (Humectant)

Xylitol

Eurphrasia extract

The conventional role of sodium chloride is taken by betaine (trimethylglycine). One of the properties of trimethylglycine is that it avoids osmosis between cells and the outside world due to differences in electrolyte concentration, and trimethylglycine is therefore identified as an osmo-protectant. The polysaccharide constituent is a negatively charged mixture of 70-90% D- Mannose 30-10% glucose, and 0-10% of other monosaccharides and is a plant derivative, for example Aloe Vera derivative.

The addition of 2-3% pentylene glycol contribute to the required humectancy. At the same time pentylene glycol assures optimal protection of the consumer product while maintaining the mucous membrane integrity.

An optional additional ingredient is eyebright extract (euphrasia) in the nasal spray. Orally, eyebright is used to treat nasal mucous membrane inflammation, allergies, allergic rhinitis, common cold, bronchial conditions and sinusitis. It also used orally for conjuctivitis, earaches, headaches, hoaresness, opthalmia, rhinitis, skin aliments, and sore throat. Eyebright is also used topically to prevent mucous and mucous membrane inflammation of the eyes. Eyebright is considered safe when used orally and appropriately. Eyebright is listed by the Council of Europe as a natural source of food flavouring.

Composition 2-Hypertonic Nasal spray

Purified Water (Solvent) Betaine (Osmo-protectant isotonic solute)

Polysaccharide constituent

Pentylene Glycol (Humectant)

Eurphrasia extract

NaCl or sea water

In the case of a hypertonic product the osmotic pressure of the solute is higher than in the cells. Higher osmotic pressure is achieved by a higher electrolyte loading.

Using a hypertonic spray may enable drainage of excessive liquid from the cells, to reduce swellings, for the treatment of sinusitis, headaches and nasal congestion. In the case of a hypertonic spray sodium chloride (or sea water) is used in combination with betaine. This maintains the original equilibrium but also effects a raising of the osmotic pressure from the cells to the environment, therefore reducing swelling.

Claims

1. Use of a composition for the manufacture of a medicament which is effective in blocking adhesion of harmful bacteria to host tissues, the composition comprising an isotonic or hypertonic formulation or a powder for the preparation thereof including an active bacteria blocking ingredient selected from extracts of plant or animal origin and/ or derivatives thereof comprising a combination of polysaccharides comprising 60-100% of D-mannose, 40-0% of D-glucose and 0-10% of other monosaccharides.

2. Use of a composition in accordance with claim 1 comprising an osmo- protectant mitigating the effect of osmosis between cells and their environment.

3. Use of a composition in accordance with claim 2 wherein the composition is saline and the osmo-protectant is sodium chloride.

4. Use of a composition in accordance with claim 2 wherein the composition is desalinated and the osmo-protectant is trimethy glycine.

5. Use of a composition in accordance with any preceding claim wherein the active ingredient is selected from extracts and/ or derivatives of aloe, in particular aloe vera and derivatives thereof.

6. Use of a composition in accordance with any preceding claim wherein the active ingredient is negatively charged.

7. Use of a composition in accordance with any preceding claim in a formulation for delivery as a spray or as a douche to the surface tissue of a recipient so as to drench the surface tissue.

8. Use of a composition in accordance with claim 7 in combination with a suitable container for delivery by a spray dispenser including a nasal, eye or ear spray dispenser, or by pipette, or as a wash, including an eye wash or ear wash or a wash for nasal inhalation.

9. Use of a composition in accordance with any preceding claim for the manufacture of a medicament for use in preventing inflammation and bacterial infections, including those caused by:

Staphylococcus epidermis;

Moraxella bovis as the source of infectious bovine keratoconjunctivitis; Staphylococcus aureus, including MRSA, which adheres to the skin and mucous tissues; bacteria involved in Otitis media and nasopharyngal comprising

Haemophilus influenza, Streptococcus penumoniae and Moraxella catarrhalis ; bacteria involved in caries such as Streptoccoccus sobrinus as acariogenic strain, Streptocossus mutans, Streptococcus salivarius,

Streptococcus gordonii and Actinomyces viscosus, Actinobacillus actinomy cetecomitans ; periodontopathogenic bacteria comprising Porphyromonas gingivalis and Streptococcus salivarius, Streptococcus oralis, Fusobacterium nucleatum and Prevotella intermedia; all oral spirochetes which are classified in the genus Treponema, comprising denticola, pectinovorum, socranskii and vincentii; Mycoplasma salivarium; microorganisms involved in nasal polyposis; and microorganisms involved in Sinusitis.

10. Use of a composition in accordance with any preceding claim for the manufacture of a medicament comprising additional active ingredients effective in combatting sleep apnoea, dry eyes, irritated or tired eyes, decongestion, hay fever, allergy or tinnitus.

11. Use of a composition in accordance with any preceding claim wherein the composition includes additional ingredients such as humectants and/or excipients, stabilisers, carriers or fillers.

12. Use of a composition in accordance with claim 11 wherein the composition includes up to 10 Wt% humectant.

13. Use of a composition in accordance with claim 12 wherin the humectant is pentene glycol.

14. Use of a composition in accordance with any preceding claim wherein the active ingredient is present in an amount in the range 1—20 wt %

15. Use of a composition in accordance with claim 14 wherein the active ingredient is present in an amount in the range 2 — 10 wt %.

16. An active ingredient for an isotonic or hypertonic formulation or a powder for the preparation thereof including an active bacteria blocking ingredient selected from extracts of plant or animal origin and/ or derivatives thereof comprising a combination of polysaccharides comprising 60-100% of D-mannose, 40-0% of D-glucose and 0-10% of other monosaccharides.

17. A composition comprising comprising an isotonic or hypertonic formulation including the active ingredient of claim 16.

18. A method of blocking adhesion of harmful bacteria to host tissues comprising applying an isotonic or hypertonic formulation including an active bacteria blocking ingredient selected from extracts of plant or animal origin and/ or derivatives thereof comprising a combination of polysaccharides comprising 60-100% of D-mannose, 40-0% of D- glucose and 0-10% of other monosaccharides.

19. The method of claim 18 comprising drenching the surface tissue of a recipient by delivering the composition as a spray or as a douche.

20. The method of claim 18 or 19 applied in preventing inflammation and bacterial infections, including those caused by:

Staphylococcus epidermis;

Haemophilus influenza, Streptococcus penumoniae and Moraxella catarrhalis ; bacteria involved in caries such as Streptoccoccus sobrinus as acariogenic strain, Streptocossus mutans, Streptococcus salivarius, Streptococcus gordonii and Actinomyces viscosus, Actinobacillus actinomy cetecomitans ; periodontopathogenic bacteria comprising Porphyromonas gingivalis and Streptococcus salivarius, Streptococcus oralis, Fusobacterium • nucleatum and Prevotella intermedia; all oral spirochetes which are classified in the genus Treponema, comprising denticola, pectinovorum, socranskii and vincentii; Mycoplasma salivarium; microorganisms involved in nasal polyposis; and microorganisms involved in Sinusitis.

21. Composition, method or use substantially as described or illustrated in the description, examples or figures.