GB2496654A

GB2496654A - Self-assembling peptides

Info

Publication number: GB2496654A
Application number: GB1119910.6A
Authority: GB
Inventors: Janice Anson; Agnieszka Milewska-Zuk; Alberto Saiani; claire Tang; Robyn Walker
Original assignee: University of Manchester; Reckitt and Colman Overseas Ltd
Current assignee: University of Manchester; Reckitt and Colman Overseas Ltd
Priority date: 2011-11-18
Filing date: 2011-11-18
Publication date: 2013-05-22
Also published as: WO2013072686A3; WO2013072686A2; GB201119910D0

Abstract

Peptide-based hydrogels in which the peptides coalesce such that they 'self-assemble' to form a hydrogel. Such hydrogels can be used to deliver pharmaceutically active compounds through mucosal tissue. The peptides have 2-20 amino acids. Preferred peptides have 6-10 amino acids (e.g. FEFEFKFK, FEFEFRFR). The peptides have been found to adhere well to mucosal tissue allowing for good delivery of pharmaceutically active compounds and may be used to treat pain, inflammation and infection of the oral cavity (e.g. sore throat).

Description

Self-Assembling Pentides The present invention is directed to peptide-based hydrogels. In particular, the present invention is directed to peptide-based hydrogels in which the peptides coalesce such that they self-assemble' to form a hydrogeL Such hydrogels can be used to deliver pharmaceutically active compounds through mucosal tissue.

Peptidcs arc short polymers of am i no acids wherein the amino acids are connectcd by peptide bonds and have an amino group at onc end and a carboxylic acid group at the othcr end. The shortest peptide is a dipeptidc. A sequence of peptidcs can be built up to form a polypeptide. Polypeptides themselves arc used to form proteins.

Polypeptidcs are known to commonly form aipha-helices and beta-sheets. Indeed, polypeptides can be specifically designed to self-assemble into alpha-helices and beta-sheets by taking advantage of biomolecular properties, intramolecular folding, the secondary structure, any electrostatic interactions and amphiphilicty.

Most of the work done in this area relates to the use of these materials to form gels which are potentially useftil in film forming or biomaterials that can be used in applications such as artificial skin and separation matrices.

US 2005/0181973 discloses self-assembling pcptidcs that include an additional domain that does not self-assemble. These materials are useful in the area of cell culture, tissue engineering and tissue repair. US 2009/0162437 discloses self-assembling peptides that have an additional domain that does not self-assemble.

US 5 670 483 discloses a self-assembling peptide which has at least 12 amino acids.

The peptides are used to form stable macroscopic membranes, US 5 955 343 also discloses polypeptides that can form stable macroscopic membranes. In this case the oligopeptides are related to a yeast DNA binding protein, zuotin.

US 2002/0160471 teaches of a polypeptide scaffold having a 3-dimensional arrangement of predetermined geometry.

There is no disclosure in the prior art regarding the use of such peptides for the preparation of formulations for delivery of an active to mucosal tissue, such as the mouth/oral cavity, throat. oesophagus, trachea, lungs, ear, eye, vagina and/or rectum.

According to a first aspect of the present invention there is provided a pharmaceutical composition comprising at least one pharmaceutically active compound and at least one peptide having 2 -20 amino acids that is capable of mediating self-assembly.

Preferably the peptide has 6 -12 amino acids. More preferably the peptide has 8 amino acids.

Preferably the one or more amino acids are selected from phenylalanine, valine, arginine, lysine, eucine, isoleucine, aspartic acid and glutamic acid.

Preferably the peptides comprise at least one amino acid having a hydrophobic side chain (a hydrophobic amino acid), and at least one amino acid having a hydrophilic side chain (a hydrophilic amino acid).

Typically the peplide comprises an amino acid sequence in which the amino acids alternate between hydrophilic amino acids and hydrophobic amino acids.

The concentration of pcptidc in the composition can be 0.1 -10% wlw. Typically, the concentration is 0.5 -5% w/w. A more typical concentration is 1 -3% w/w.

In an embodiment of the invention, the hydrophobic amino acids are selected from the group consisting of phenylalanine, valine, leucine and isoleucine and the hydrophilic amino acids are selected from the group consisting of arginine, lysine, aspartic acid and glutamic acid.

In a first preferred embodiment the hydrophobic amino acid can be selected to be phenylalaninc (Phe) and the hydrophilic component can be selected to be a combination of glutamic acid (Glu) and lysine (Lys). In more prcfcned embodiments the amino acid sequence of the peptide is Phe-GIu-Phc-Glu-Phe-Lys-Phe-Lys or Phe-Glu-Phe-Lys-Phe-Glu-Phc-Lys.

In a second preferred embodiment the hydrophobic amino acid can be selected to be phenylalanine (Phe) and the hydrophilic component can be selected to be a combination of glutamic acid (Glu) and arginine (Arg). In a more preferred embodiments the amino acid sequence of the peptide is Phe-Glu-Phe-Glu-Phe-Arg-Phe-Arg.

In a third preferred embodiment the hydrophobic amino acid can be selected to be valine (Val) and the hydrophilic component can be selected to be a combination of glutamic acid (Glu) and lysine (Lys). In a more preferred embodiment the amino acid sequence of the peptide is \Tal-Glu-Val-Glu-Val-Lys-Val-Lys or Val-Glu-Val-Lys-Val-Glu-Val-Lys.

In a fourth preferred embodiment the hydrophobic amino acid can be selected to be phenylalanine (Phe) and the hydrophilic component can be selected to be a combination of glutamie acid (Glu), lysine (Lys) and arginine (Arg). In more preferred embodiments the amino acid sequence of the peptide is Phe-Glu-Phe-Glu- Phe-Arg-Phe-Lys, Phe-Glu-Phe-Arg-Phe-Lys-Phe-Arg, or Phe-Glu-Phe-Arg-Phe-Arg-Phe-Lys.

The pharmaceutically active compound present in the pharmaceutical compositions of the present invention may be any pharmaceutically active agent that is suitable for mucosal delivery. For example, the pharmaceutically active compound may be selected from one or more of the following categories of pharmaceutically active compounds: anti-cancer agents, antibacterial agents, antifhngal/yeast agents, antimicrobial peptides, anti-inflammatory agents, antihistamine agents, antiseptic agents, decongestants, local anaesthetic agents, ophthalmic agents (e.g. drugs to treat glaucoma or other eye disorders), cough suppressants, expectorants, prebiotics and probiotics.

In a particular embodiment, the at least one pharmaceutically active compound can be selected from the group consisting of 2,4-dichlorobenzyl alcohol (DCBA), amyl metacreso 1 (AMC), hexylresorcinol, flurbiprofen, lidocaine, benzocaine, cetylpyridinium chloride, dequalinium chloride, menthol, ambroxol hydrochloride, dextromcthorphan hydrobromidc, phcnylcphrine and guaifcncsin. Preferably the at least one pharmaceutically active compound is selected from the group comprising 2,4-dichlorobenzyl alcohol (DCBA), amyl metacresol (AMC), hexylresorcinol, flurbiprofen, lidocaine, benzocaine, prebiotics (such as oligofructose, inulin and others), probiotics (such as L. acidophilus, L. reuteri, L. rhamnosus, L. casci, L. paracasei, L. plantarum group, L. brevis, L. fcrmcntum, L. salivarius, Streptococcus salivarius, B. bifidum, B. longum, B. lactis, B. infantis, Bacillus Coagulans and others), natural extracts and herbs (aloe vera, sage, thyme, sandalwood, niaouli, nigclla sativia, echinacca, tea tree, propolis, hyssop, peppermint, slippery elm, elderberry, cohsfoot, eucalyptus oil, chamomile oil, rosemary extracts, citrus extract, cardamom and others), cooling ingredients (e.g. menthol), warming ingredients and any other beneficial agents. More preferred pharmaceutically active compounds are flurbiprofcn, lidocaine and benzocainc.

At least one pharmaceutically active compound can be present at a level of 0.1 -10% w!w. Typically, the concentration is 1 -2% w/w.

The composition can be in the form of a lozenge, a liquid-filled lozenge, a liquid, a syrup, a powder, a tablet, a chewable tablet, a spray, a gel, a capsule, a pastilic, a mouthwash, a jelly, a chew or a gum.

According to a second aspect of the present invention there is provided a peptide having 4 -16 amino acids that is capable of mediating self-assembly wherein the amino acids are selected from phenylalanine, valine, arginine, lysine, leucine, iso leucinc, aspartic acid and glutamic acid.

Preferably the peptide has 6 -1 0 amino acids. More preferably the peptide has 8 amino acids.

Preferably the peptide comprises at least one amino acid having a hydrophobic side chain, and at least one amino acid having a hydrophilic side chain.

Typically the peptidc comprises an amino acid sequence in which the amino acids alternate between hydrophilic amino acids and hydrophobic amino acids.

In a first preferred embodiment the hydrophobic amino acid can be selected to be phenylalanine (Phe) and the hydrophilic component can be selected to be a combination of glutamic acid (Glu) and lysine (Lys). In more preferrcd embodiments thc amino acid sequcncc of the peptide is Phc-Glu-Phe-Glu-Phe-Lys-Phc-Lys or Phe-Glu-Phe-Lys-Phe-Glu-Phe-Lys.

In a second preferred embodiment the hydrophobic amino acid can be selected to be phenylalanine (Phe) and the hydrophilic component can be selected to be a combination of glutamic acid (Glu) and arginine (Arg). In more preferred embodiments the amino acid sequence of the peptide is Phe-Glu-Phe-Glu-Phe-Arg-Phe-Arg or Phc-Glu-Phe-Arg-Phe-G Iu-Phe-Arg.

In a third preferred embodiment the hydrophobic amino acid can be selected to be valine (Val) and the hydrophilic component can be selected to be a combination of glutamic acid (Glu) and lysine (Lys). In a more preferred embodiment the amino acid scqucnce of the pcptide is Val-Glu-Val-Glu-Val-Lys-Val-Lys or Val-Glu-Val-Lys-Val-Glu-Val-Lys In a fourth preferred embodiment the hydrophobic amino acid can be selected to be phenylalanine (Phe) and the hydrophilic component can be selected to be a combination of glutamic acid (Glu), lysine (Lys) and arginine (Arg). In more prefered embodiments the amino acid sequence of the peptide is Phe-Glu-Phe-Glu- Phc-Arg-Phe-Lys, Phe-G lu-Phe-Arg-Phe-Lys-Phc-Arg, or Phe-G lu-Phc-Arg-Phe-Arg-Phe-Lys.

According to a third aspect of the present invention there is provided a hydrogcl/ viscous liquid comprising more than one of the peptides as described in the second aspect of the present invention wherein the more than one peptides form a matrix that is hydratcd to form said gel/viscous liquid. The matrix can be in the fbrm of a bcta-sheet.

According to a iburth aspect of the present invention there is provided a method of treating pain, inflammation, and infection of the oral cavity of an individual which comprises administering to an individual a composition as described in the first aspect of the present invention. Typically the composition is administered to an individual having a sore throat.

According to a fifth aspect of the present invention there is provided the use of a composition as described in the first aspect of the present invention fbr the treatment of a sore throat in an individual.

According to a sixth aspect of the present invention there is provided the a composition as described in the first aspect of the present invention ±1w use in the treatment of an eye infection or disorder.

According to an seventh aspect, the present invention provides a method of treating an eye infection or disorder in an individual in need of such treatment, the nicthod comprising administering a therapeutically effective amount of a composition as defined in the first aspect of the present invention.

According to an eighth aspect of the present invention there is provided the a composition as described in the first aspect of the present invention fbr use in the treatment of an ear infection or disorder.

According to an ninth aspect, the present invention provides a method of treating an eye infection or disorder in an individual in need of such treatment, the method comprising administering a therapeutically effective amount of a composition as defined in the first aspect of the present invention.

According to a tenth aspect of the present invention there is provided a composition as described in the first aspect of the present invention that is substantially water free and ibrms a hydrogel/viscous liquid upon the addition of water.

According to a eleventh aspect of the present invention there is provided the use of a composition as described in the first aspect of the present invention for the delivery of a drug through any mucosal tissue in an individual.

The mucosal tissue may be selected from mucosal tissues present in the mouth, throat, oesophagus, frachea, lungs, ear, eye, vagina and/or rectum.

As used herein the term pharmaceutically active compound' covers pharmaceutically activc compounds and pharmaceutically acceptable salts and esters thereof.

Example embodiments of the present invention will now be described, with reference to the accompanying Figure which illustrates an In-Vitro Oral Retention (IVOR) model used to simulate the flow of the composition over a mucosal surface.

The compositions were prepared in the following way.

The required amount of octapeptide was suspended in HPLC grade water (either 100% or 70% of the final volume required) to obtain the desired concentration (10- 40 mg mL1). To dissolve the pcptidc the sample was vortcxcd, sonicated and left at 80-85 °C for a period of up to several hours depending on the peptidc sequence and its concentration. The pH of the sample was not adjusted, resulting in samples with final ph values of Ca. 2-3 (depending on the peptide concentration due to residual TFA). The samples were then cooled and maintained at room temperature for -1 2 hours (overnight) to enable gelation.

Actives were loaded differently depending on their solubility in ethanol. Insoluble actives such as flurbiprofen were added as powder on top of the gel/viscous solution formed, either followed by ethanol (30% of the final volume required) or added to geL'viscous solution fully water based (100% of water in the final formula) to form a suspension. Soluble actives such as lidocaine hydrochloride monohydrate were either pre-dissolvcd in ethanol (30% of the final volume required) and added to the gel/viscous solution formed or added as powder on top of the gel/viscous solution formed. To ensure homogeneous samples were obtained, the sampcs were vortexed and sonicated immediately after the active loading. The samples were then maintained at room temperature for 12 hours (overnight) to allow them to settle.

The final pH of the sample can be adjusted to pH 4-7 using sodium hydroxide solutions (5 M, e.g. 5-20 gL for 30 mg mU4 samples of Phe-Glu-Phe-Glu-Phe-Lys-Phe-Lys) after 6 hours.

At any step the air bubbles resulting from the sample mixing could be removed by centriftigating the samples at 1000 rpm for 30-60 seconds.

Example compositions arc detailed in Table 1.

Example 1 2

Peptidc Chain Phe-Glu-Phe-Glu-Phe-Lys-Phe-Glu-Phe-Gi u-Phc-Phc-Lys Arg-Phe-Arg Concentration (mg/mI) 30 20 Active Flurbiprofen Flurbiprofen Concentration of active 16.2mglmi 16.2mg/mi in the sample Theoretical amount of 1.62mg 1.62mg active applied on the slope The retention profiles of the hydrogcl compositions containing flurbiprofen at a concentration of 16.2 mg/ml were determined. The retention profiles were determined from the calculation of flurbiprofen concentration from each time point using the IVOR model shown in Figure 1. The Il/OR model is an in-vitro mucosa testing model that was used in this study to test samples' adhesion properties to mucosa and aetives' release/retention profile over set period of time. The main part of it is a moveable ramp, the slope of which can be modified to mimic different conditions. It is also possible to maintain constant temperature of the model during a test. Visking membrane, which is semi-or partially permeable cellulose based membrane, was used to mimic mucosa surface.

For samples with flurbiprofen, the membrane/tissue was pre-soaked in artificial saliva and conditioned on the slope, which was set at 300, of the IVOR model for 15 minutes with a flow rate of 2m1/min of artificial saliva. The flow was then stopped and I OOgl of sample was applied to the top of the slope and left for one minute. The flow was then re-started and the eluate was collected over ten minute intervals for one hour.

Each 10 minute sample was collected in a 50m1 volumetric flask, each sample was made up to the required volume with methanol.

The samples were analysed using HPLC. The HPLC was set up as follows: Column: Zorbax Eclipse XDB-C18, 150 x 4.6mm 5R or equivalent Phase: 660 ml methanol: 340 ml deionised water: I ml ortho-phosphoric acid Flow rate: 1.5 mLlmin Wave length: 2SOnm 4BW ref 600nm 100BW Run time: 10 minutes Column temperature: 25°C Injection: 8Op.l The maximum amount of flurbiprofen present in a collected sample is 1.62 mg in 50 ml or 0.032 mg/mI. A graph was plotted for peak area against concentration of flurbiprofen. Graph 1 shows the concentration levels to be linear over the range 0.002 to 0.07 mg/mI.

Fiurbiprofen y = 49639x -6.2149 p2 = 1 III I::II;;EEI:ffT:ffE 0 0.01 0.02 0.03 0.04 0.05 0.06 0.07 0.08 Concentration (mg/mi) Graph 1: Plot of area against concentration of flurbiprofen.

Graph I represents a calibration curve, which was generated using standards of known amount of flurbiprofen. It shows that the amount of flurbiprofen was linear over the concentration range 0.002 to 0.07 mg/mI. Therefore, this graph was used to determine the amount of flurbiprofen in an unknown sample (collected eluate from the test) by comparing the unknown to a set of standards samples of known active amount.

In example 1 the amount of flurbiprofen remaining on the slope after 10 minutes is 26.3% (0.36mg). This decreased to 1.6% (0.02mg) after 60 minutes based on actual recovery. Recoveries ranged from 81 to 86% based on a theoretical value of 1.63 mgm1.

In example 2 the amount of flurbiprofen remaining on the slope after 10 minutes is 47.3% (0.67mg). This decreased to 6.1% (0.09mg) after 60 minutes. Recoveries ranged from 83 to 88% based on a theoretical value of 1.64 mg/mi.

As a control, a lozenge was applied to the slope. The lozenge sample was applied over 6 minutes (representing someone sucking the lozenge).

A comparison between the lozenge and peptide compositions is shown in Graph 2.

This does not account for the initial flurbiprofen loading amount. ! : N N. -4

0 0 __________ ______ Time (mm) Graph 2: Comparison between flurbiprofen retention profiles for Examples 1 (Phe- G lu-Phe-Glu-Phe-Lys-Phe-Lys -FEFEFKFK) & 2 (Phe-Glu-Phe-G lu-Phe-Arg-Phe-Arg -FEFEFRFR), and a lozenge.

This comparison shows the peptide compositions retaining the grcatest percentage of fiurbiprofen on the slope.

An advantage of the present invention is that there is provided a pharmaceutical tO composition that exhibits excellent retention properties for an active compound on a mucosal surface.

Further modifications and improvements can be made without departing from the scope of the invention described herein.

Claims

<claim-text>Claims: 1. A pharmaceutical composition comprising at least one pharmaceutically active compound and a peptide having 2-20 amino acids that is capable of mediating self-assembly.</claim-text> <claim-text>2. A pharmaceutical composition as claimed in Claim 1 wherein the peptide has 6-10 amino acids.</claim-text> <claim-text>3. A pharmaceutical composition as claimed in Claim 2 wherein the pcptide has 8 amino acids.</claim-text> <claim-text>4. A pharmaceutical composition as claimed in any of the preceding Claims wherein the one or more amino acids are selected from phenylalanine, valine, arginine, lysine, leucine, isoleucine, aspartie acid and glutamic acid.</claim-text> <claim-text>5. A pharmaceutical composition as claimed in any of the preceding Claims wherein the peptides comprise at least one amino acid having a hydrophobic side chain, and at least one amino acid having a hydrophilie side chain.</claim-text> <claim-text>6. A pharmaceutical composition as claimed in Claim 5 wherein the peptide comprises an amino acid sequence in which the amino acids altematc between hydrophilic amino acids and hydrophobic amino acids.</claim-text> <claim-text>7. A pharmaceutical composition as claimed in any of the preceding Claims wherein the concentration ofpeptide in the composition is 0.1 -10% w/w.</claim-text> <claim-text>8. A pharmaceutical composition as claimed in Claim 7 wherein the concentration is 0.5 -5% w!w.</claim-text> <claim-text>9. A pharmaceutical composition as claimed in Claim 8 wherein the concentration is 1 -3 w/w%.</claim-text> <claim-text>0. A pharmaceutical composition as claimed in any of thc preceding Claims wherein the hydrophobic amino acid is selected to be phenylalanine (Phe) and the hydrophilic component is selected to be a combination of glutamic acid (Glu) and lysine (Lys).</claim-text> <claim-text>II. A pharmaceutical composition as claimed in Claim 10 wherein the amino acid sequence of the peptide is Phe-Glu-Phe-Glu-Phe-Lys-Phe-Lys.</claim-text> <claim-text>12. A pharmaceutical composition as claimed in Claim 10 wherein the amino acid sequence of the pcptidc is Phe-Glu-Phc-Lys-Phc-Glu-Phe-Lys.</claim-text> <claim-text>13. A pharmaceutical composition as claimed in any of Claims 1 -9 wherein the hydrophobic amino acid is selected to be phenyalanine (Phe) and the hydrophilic component is selected to be a combination of glutamic acid (Glu) and arginine (Arg).</claim-text> <claim-text>14. A pharmaceutical composition as claimed in Claim 13 wherein the amino acid sequence of the peptide is Phe-Glu-Phe-Glu-Phe-Arg-Phe-Arg.</claim-text> <claim-text>15. A pharmaceutical composition as claimed in Claim 13 wherein the amino acid sequence of the pcptidc is Phe-Glu-Phc-Arg-Phc-Glu-Phe-Arg.</claim-text> <claim-text>16. A pharmaceutical composition as claimed in any Claims -9 wherein the hydrophobic amino acid is selected to be valine (Val) and the hydrophilic componcnt is selected to be a combination of glutamic acid (GIn) and lysinc (Lys).</claim-text> <claim-text>17. A pharmaceutical composition as claimed in Claim 16 wherein the amino acid sequence of the pcptidc is Val-Glu-Val-Glu-Val-Lys-Val-Lys.</claim-text> <claim-text>18. A pharmaceutical composition as claimed in Claim 16 wherein the amino acid sequence of the peptide is Val-Glu-Val-Lys-Val-Glu-Val-Lys.</claim-text> <claim-text>9. A pharmaceutical composition as claimed in any Claims I -9 wherein thc hydrophobic amino acid is selected to be phenylalanine (Phe) and the hydrophilic component is selected to be a combination of glutamic acid (Glu), lysine (Lys) and arginine (Arg).</claim-text> <claim-text>20. A pharmaceutical composition as claimed in Clam 19 wherein the amino acid sequence of the peptide is Phe-Glu-Phe-Glu-Phe-Arg-Phe-Lys.</claim-text> <claim-text>21 A pharmaceutical composition as claimed in Clam 19 wherein the amino acid sequence of the pcptidc is Phe-Glu-Phc-Arg-Phc-Lys-Phe-Arg.</claim-text> <claim-text>22. A pharmaceutical composition as claimed in Clam 19 wherein the amino acid sequence of the peptide is Phc-Glu-Phe-Arg-Phe-Arg-Phe-Lys.</claim-text> <claim-text>23. A pharmaceutical composition as claimed in any of the preceding Claims wherein the at least one pharmaceutically active compound is a cancer drug, anti-bacterial or anti-microbial drug/peptide, an antibiotic and anti-inflammatory drug, and anti-yeast infection drug, anti-histaminic drug or selected from the group consisting of 2,4-dichlorobenzyl alcohol (DCBA), amy] metacresol (AMC), hexylresorcinol, flurbiprofen, lidocaine, benzocaine, cetylpyridinium chloride, dequal inium chloride, menthol, ambroxo 1 hydrochloride, dcxtromethorphan hydrobromide, phenylephrinc, guaifcnesin, prebiotics (such as oligofruetose, inulin and others), probiotics (such as L. acidophilus, L. reuteri, L. rhamnosus, L. casci, L. paracasei, L. plantarum group, L. brevis, L. fermentum, L. salivarius, Streptococcus salivarius, B. bifidum, B. longum, B. lactis, B. infantis, Bacillus Coagulans and others), natural extracts and herbs (aloe vera, sage, thyme, sandalwood, niaouli, nigella sativia, cchinacea, tea tree, propolis, hyssop, peppermint, slippery elm, elderberry, coltsfoot, eucalyptus oil, chamomile oil, rosemary extracts, citrus extract, cardamom and others), cooling ingredients (e.g. menthol), warming ingredients and any other beneficial agents.</claim-text> <claim-text>24. A pharmaceutical composition as claimed in Claim 23 wherein the at least one pharmaceutically active compound is selected from the group comprising 2,4-dichlorobcnzyl alcohol (DCBA), amyl metacrcsol (AMC), hexylresorcinol, flurbiprofen, lidocainc, benzocaine.</claim-text> <claim-text>25. A pharmaceutical composition as claimed in Claim 24 wherein the pharmaceutically active compound is selected from lidocaine, benzocaine or Ilurbiprofen.</claim-text> <claim-text>26. A pharmaceutical composition as claimed in any the preceding Claims wherein the at least one pharmaceutically active compound is present at a level of is 0.1-lO%w!w.</claim-text> <claim-text>27. A pharmaceutical composition as claimed in Claim 26 wherein the at least one pharmaceutically active compound is present at a level of is I -2% w/w.</claim-text> <claim-text>2K A pharmaceutical composition as claimed in any the preceding Claims wherein the composition is in the form of a lozenge, a liquid-filled lozenge, a liquid, a syrup, a powder, a tablet, a chewable tablet, a spray, a gel, a capsule, a mouthwash, a jelly, a chew, a pastille or a gum.</claim-text> <claim-text>29. A peptide having 2 20 amino acids that is capable of mediating self-assembly whercin the amino acids are selected from phenylalanine, valine, arginine, lysinc, Icucinc, isoleucine, aspartic acid and glutamic acid.</claim-text> <claim-text>30. A peptide as claimed in Claim 29 wherein the peptide has 6-10 amino acids.</claim-text> <claim-text>31. A peptide as claimed in Claim 30 wherein the peptide has 8 amino acids.</claim-text> <claim-text>32. A pcptidc as claimed in any of Claims 29 -31 wherein the peptide comprises at least one amino acid having a hydrophobic side chain, and at least one amino acid having a hydrophilic side chain.</claim-text> <claim-text>33. A peptide as claimed in Claim 32 wherein the peptide comprises an amino acid sequence in which the amino acids alternate between hydrophilic amino acids and hydrophobic amino acids.</claim-text> <claim-text>34. A peptide as claimed in any of Claims 29-33 wherein the hydrophobic amino acid is selected to be phenylalanine (Phe) and the hydrophilic component is selected to be a combination of glutamic acid (Glu) and lysine (Lys).</claim-text> <claim-text>35. A peptide as claimed in Claim 34 wherein the amino acid sequence of the peptide is Phe-Glu-Phe-Glu-Phe-Lys-Phe-Lys.</claim-text> <claim-text>36. A peptide as claimed in Claim 34, wherein the amino acid sequence of the peptide is Phc-Glu-Phc-Lys-Phe-Glu-Phc-Lys.</claim-text> <claim-text>37. A peptide as claimed in any ofClaims 29-33 wherein the hydrophobic amino acid is selected to be phcnylalanine (Phe) and the hydrophilic component is selected to be a combination of glutamic acid (Glu) and argininc (Arg).</claim-text> <claim-text>38. A peptide as claimed in Claim 37 wherein the amino acid sequence of the peptide is Phe-Glu-Phe-G lu-Phe-Arg-Phe-Arg 39. A peptidc as claimed in Claim 37 wherein the amino acid sequence of the peptide is Phe-Glu-Phe-Arg-Phe-Glu-Phe-Arg.40. A peptide as claimed in any of Claims 29-33 wherein the hydrophobic amino acid is selected to be valine (Va]) and the hydrophilic component is selected to be a combination of glutamic acid (Glu) and lysine (Lys).41. A peptide as claimed in Claim 40 wherein the amino acid sequence of the peptide is Val-Glu-Val-GI u-Va]-Lys-Val-Lys.42. A peptide as claimed in Claim 40 wherein the amino acid sequence of the peptide is Val-Glu-Val-Lys-Val-Glu-Val-Lys..43. A peptidc as claimed in any ofClaims 29 -33 wherein the hydrophobic amino acid is selected to be phenylalanine (Phe) and the hydrophilic component is selcctcd to be a combination of glutamic acid (Glu), lysinc (Lys) and argininc (Arg).44. A peptide as claimed in Claim 43 wherein the amino acid sequence of the peptide is Phe-Glu-Phe-G lu-Phe-Arg-Phe-Lys.45. A peptide as claimed in Claim 43 wherein the amino acid sequence of the peptide is Phe-Glu-Phe-Arg-Phe-Lys-Phe-Arg.46. A peptide as claimcd in Claim 43 wherein the amino acid scqucncc of the peptide is Phe-Glu-Phe-Arg-Phe-Arg-Phe-Lys.47. A hydrogel or viscous liquid comprising more than one of the peptides of Claims 29 -46 wherein the more than one peptide form a matrix of beta sheets that are hydrated to form said gel or viscous liquid.48. A method of treating pain, inflammation, and infection of the oral cavity of an individual which comprises administering to an individual a composition as claimed in any of Claims 1 -28.49. A method as claimed in Claim 48 wherein the composition is administered to an individual having a sore throat.50. A method for the delivery of a drug through mueosal tissue which comprises administering to an individual a composition as claimed in any of Claims 1 -28.50. The use ofa composition as claimed in any of Claims I -28 for the treatment of a sore throat in an individual.51. A composition as claimed in any of Claims 1 -28 that is substantially water free and forms a hydrogel or viscous liquid on addition of water.</claim-text>