Compositions, Methods and/or Devices for Prevention and/or Treatment of Dry Eye Disorders

Abstract

The present disclosure relates to compositions, methods and devices for treating, reducing or preventing one or more eye disorders, particularly dry eye disorders, in a subject by administering an amount of one or more fatty acids and/or fatty acid esters therapeutically effective to inhibit lipase activity while permitting bacterial growth or without substantially altering the dynamic microbial community of the eye. Typically, the fatty acids and/or fatty acid esters are C.sub.8 to C.sub.16 fatty acids and/or fatty acid esters.

Claims

1. A composition for treating or preventing a dry eye disorder in a subject, wherein, the composition comprises an amount of one or more C.sub.8 to C.sub.16 fatty acids and/or fatty acid esters therapeutically effective to inhibit lipase activity in an eye of the subject without substantially altering the dynamic microbial community of the eye.

2. A composition according to claim 1 wherein the fatty acids and/or fatty acid esters are C.sub.10 to C.sub.14 fatty acids and/or fatty acid esters.

3. A composition according to claim 1, wherein the fatty acids and/or fatty acid esters are one or more of the following fatty acids and/or fatty acid esters: C.sub.8, C.sub.10, C.sub.11, C.sub.12 or C.sub.14.

4. A composition according to claim 1, wherein the fatty acids and/or fatty acid esters are selected from the group consisting of capric acid, caprylic acid, myristic acid or combinations thereof.

5. A composition according to claim 1, wherein the fatty acid and/or related fatty acid ester is glycerol monolaurate, lauric acid or a combination thereof.

6. A composition according to claim 1 further comprises a therapeutically effective amount of androgen or androgen analogue.

7. A composition according to claim 6 wherein the androgen and/or androgen analogue is selected from one or more of the following: dehydroepiandrosterone (DHEA), androsterone, testosterone and dihydrotestosterone.

8. A composition according to claim 1 further comprises a therapeutically effective amount of an anti-inflammatory agent.

9. A composition according to claim 8 wherein the anti-inflammatory agent is selected from one or more of the following: azithromycin, cyclosporine A, omega-3 fatty acids and transforming growth factor beta (TGF-).

10. A composition according to claim 1, wherein the composition is suitable for topical administration to an eye.

11. A composition according to claim 10, wherein the topical administration is in the form of an ointment, cream, eye drops or released from an ophthalmic device.

12. A composition according to claim 11, wherein the ophthalmic device is a contact lens.

13. The composition of claim 11, wherein the concentration of fatty acids and/or fatty acid esters is about 0.01 to 50 g/ml in the eye drops.

14. The composition of claim 11 wherein the concentration of fatty acids and/or fatty acid esters is about 0.01 to 50 g/ml in the composition associated with the contact lens.

15. The composition of claim 11 wherein the concentration of fatty acids and/or fatty acid esters is about 0.00001% to 0.005% % by weight of the total volume of the eye drops.

16. A composition according to claim 11, wherein the amount of the fatty acids and/or fatty acid esters included in the ointment or the cream is in a concentration of about 0.005% to 0.05% weight of the total weight of the ointment or the cream.

17. A composition according to claim 11, wherein the amount of glycerol monolaurate included in the eye drops is in a concentration of about 0.01 to 50 g/ml.

18. A composition according to claim 11, wherein the amount of lauric acid included in eye drops is in a concentration of about 0.01 to 50 g/ml.

19-20. (canceled)

21. A composition for treating or preventing a dry eye disorder in a subject, wherein the composition comprises an amount of one or more C8 to C16 fatty acids and/or fatty acid esters therapeutically effective to inhibit lipase activity in an eye of the subject while permitting bacterial growth.

22-23. (canceled)

24. A method for treating or preventing a dry eye disorder in a subject by administering an amount of one or more C.sub.8 to C.sub.16 fatty acids and/or fatty acid esters therapeutically effective to inhibit lipase activity without substantially altering the dynamic microbial community of the eye.

25-45. (canceled)

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0058] Features, aspects, and advantages of the present disclosure will become better understood with regard to the following description, appended claims, and accompanying figures.

[0059] FIGS. 1A, 1B, 1C, 1D, and 1E shows the effect of various g/ml concentrations of glycerol monolaurate on growth of several strains of bacteria.

[0060] FIGS. 2A, 2B, 2C, 2D, and 2E shows the effect of various g/ml concentrations of lauric acid on growth of several strains of bacteria.

[0061] FIGS. 3A, 3B, 3C, 3D, and 3E shows the effect of various g/ml concentrations of glycerol monolaurate on the lipase activity of several strains of bacteria.

[0062] FIGS. 4A, 4B, 4C, 4D, and 4E shows the effect of various g/ml concentrations of lauric acid on the lipase activity of several strains of bacteria.

[0063] FIGS. 5A and 5B shows percentage reduction of lipase in strains cultured with various g/ml concentrations of glycerol monolaurate or lauric acid for 24 hours.

DETAILED DESCRIPTION OF THE INVENTION

[0064] The present disclosure is described in further detail with reference to one or more embodiments, some examples of which are illustrated in the accompanying drawings. The examples and embodiments are provided by way of explanation and are not to be taken as limiting to the scope of the disclosure. Furthermore, features illustrated or described as part of one embodiment may be used by themselves to provide other embodiments and features illustrated or described as part of one embodiment may be used with one or more other embodiments to provide further embodiments. The present disclosure covers these variations and embodiments as well as other variations and/or modifications.

[0065] The term comprise and its derivatives (e.g., comprises, comprising) as used in this specification is to be taken to be inclusive of features to which it refers, and is not meant to exclude the presence of additional features unless otherwise stated or implied.

[0066] The features disclosed in this specification (including accompanying claims, abstract, and drawings) may be replaced by alternative features serving the same.sub.i equivalent or similar purpose, unless expressly stated otherwise.

[0067] It will be understood that the invention disclosed and defined in this specification extends to all alternative combinations, of two or more of the individual features mentioned or evident from the text or drawings. All of these different combinations constitute various alternative aspects of the invention.

[0068] The subject headings used in the detailed description are included for the ease of reference of the reader and should not be used to limit the subject matter found throughout the disclosure or the claims. The subject headings should not be used in construing the scope of the claims or the claim limitations.

[0069] As discussed herein, it has been found that a C.sub.8 to C.sub.16 fatty acids and/or fatty acid ester, for example, glycerol monolaurate and/or lauric acid, are effective to inhibit lipase activity and thus, useful to treat, reduce and/or prevent dry eye. The invention disclosed herein has been found useful for alleviating symptoms associated with dry eye disorders. The invention disclosed herein has also been found useful for preventing or reducing dry eye, including when associated with contact lens wear. The present disclosure is also directed to methods of for treating, reducing or preventing such diseases or conditions.

[0070] Dry eye is a disorder of the eye due to tear deficiency or excessive evaporation, which causes damage to the ocular surface and is associated with symptoms of ocular discomfort, such as itchiness, irritation foreign body sensation, redness, photophobia, pain and paradoxical tearing from corneal irritation. Dry eye disorders have been attributed to either decreased tear production (aqueous-deficient dry eye) and/or excessive tear evaporation (evaporative dry eye). Dry eye disorders may be caused by one or more of the following: the wearing of the ophthalmic device such as a contact lens, Sjgren's syndrome, an autoimmune disorder, non-Sjgren aqueous-deficient Dry eye disorder resulting from lacrimal gland insufficiency, lacrimal duct obstruction, meibomian gland disease, blepharitis, eyelid aperture disorders, conjunctival disorders and/blink disorders

[0071] Glycerol monolaurate (also referred to as GML) is the fatty acid ester of lauric acid and glycerol. It is commonly used as a surfactant, emulsifier and preservative. It is used as a food additive (for example in ice-cream) or used in cosmetics and soaps. The structure of glycerol monolaurate is shown below:

##STR00001##

[0072] Lauric acid is a fatty acid commonly used in the production of cosmetics and soaps. The structure of lauric acid is shown below:

##STR00002##

[0073] As used herein reference to a fatty acid or fatty acid ester by the nomenclature C.sub.x is reference to a fatty acid or fatty acid ester with x carbon atoms in a main chain or backbone. For example, C.sub.8 to C.sub.16 fatty acids and/or fatty acid esters have a main chain of 8 to 16 carbon atoms. The fatty acids or fatty acid esters may be saturated or unsaturated. Saturated fatty acid or fatty acid esters are preferred.

[0074] The term androgen refers to a class of compounds that bind to androgen receptors. Androgens are typically steroid hormones and include, for example, testosterone, dihydrotestosterone and androstenedione.

[0075] The terms treating or treatment refer to administering to a subject a therapeutically effective amount of an active such that the subject has an improvement in the condition to be treated (e.g. dry eye). Treatment may prevent worsening of the condition, improve the condition, but may not provide a complete cure for the condition. Efficacy of treatment may be determined by clinical assessment including the Schirmer test without anaesthesia, tear breakup time (TBUT), phenol thread test, corneal staining or tear film triglyceride levels.

[0076] The terms preventing or prevention refer to administering to a subject a therapeutically effective amount of an active, such that the signs and/or symptoms of a condition (e.g. dry eye) are averted, delayed or significantly reduced in frequency in the subject, relative to a subject who does not receive the composition. Prevention does not require that the condition or symptoms are permanently avoided. In addition, the term prevention is used in its clinical sense to mean inhibit a disease, condition or disorder from occurring, rather than in an absolute sense of making it impossible for the disease, condition or disorder to ever occur in a given subject. Hence, inhibition of progression to disease, disorder or reduced new disease or disorder amounts to prevention within the meaning of this specification, even if there is pre-existing disease or disorder.

[0077] The terms therapeutically effective amount or effective amount refer to an amount of an active that results in an improvement or remediation of the symptoms of a disease or condition.

[0078] The term ophthalmic device refers to an object that resides in or on the eye. The device may provide optical correction or may be cosmetic. Ophthalmic devices include but are not limited to contact lenses (including soft contact lenses), intraocular lenses, onlay lenses, ocular inserts, punctal plugs, and optical inserts. The ophthalmic devices include contact lenses, such as soft contact lenses, made from silicone elastomers or hydrogels, which include, but are not limited, to silicone hydrogels and fluorohydrogels. The ophthalmic devices may be single-use devices e.g. single-use or daily contact lenses.

[0079] The term administering or administration means placing the active, composition or ophthalmic device onto the surface of the eye, or in the eye and/or ocular adnexa for example, lid margins, puncta, skin around the eye lids of a subject or administering it orally. Typically such a device (for example, a soft contact lens) is in contact with the anterior surface of the subject's eye for a length of time such as 8 to 16 hours daily. Alternatively, the active or composition may be placed into or onto an ocular insert as a method of drug delivery. Typically such an ocular insert is inserted into the space between the lids and the sclera (fornix) and gradually releases the drug. Alternatively, a biodegradable collagen lens soaked in the active or composition may be placed onto the surface of the eye, or inserted into the eye, of a subject. Typically the collagen lens slowly dissolves and improves patient symptoms. Alternatively, the active or composition may be incorporated into an ointment as a method of drug delivery. Typically, the ointment may be applied into the space between the lids and the sclera of the eye or applied onto the lid margins.

[0080] As used herein without substantially altering the dynamic commensal microbial community of the eye means without substantially altering the growth, viability, numbers, relative amounts and/or types of commensal bacteria, fungi or viruses commonly found or pre-existing in the eye. Typically, the commensal bacteria referred to are those bacterial types at levels commonly found in a healthy eye. Determining the bacterial component of the dynamic commensal microbial community associated with the eye to assess if it is substantially altered, may be by any suitable method including by taking an ocular swab of a subject and then (a) plating the bacteria from the swab onto agar plates to determine number of colonies, or (b) sequencing 16s ribosomal DNA or RNA. 16S rRNA gene sequences contain hypervariable regions that can provide species-specific signature sequences useful for bacterial identification.

[0081] In some embodiments, the minimal antibacterial activity is a 10% or 5% reduction numbers of total bacteria, or of a specific type of commensal bacteria, as measured by any suitable method including those described herein.

[0082] As used herein while permitting bacterial growth means that there is sufficiently low bactericidal or bacteriostatic activity so that bacteria, particularly commensal bacteria of the eye, are capable of growth. Determining bacterial growth can be by any suitable method including those described herein, including as per Example 1.

[0083] The subject is a subject that that has one or more of the following: suffers from dry eye disorder, is at risk of suffering from dry eye disorder, is at particular risk if dry eye disorder is developed, is a contact lens wearer and a suitable candidate for wearing contact lenses. The subject may suffer from or be at risk of suffering from other disease states disclosed herein. The subject may be a human or an animal subject. The subject is preferably human. A subject may be identified as suffering from or at risk of developing a dry eye disorder using any one of the following assessment methods: Schrimer test without anaesthesia, tear break-up time (TBUT), lipid layer appearance, phenol thread test, corneal staining, telanglectasia, lip wiper epithellopathy, gland expressibility, meibography, intraocular pressure and Ocular Surface Disease Index (OSDI) questionnaire to assess the subject's perception of dry eye severity.

[0084] Certain compositions of the present invention may be ophthalmic compositions, which are compositions suitable for administration to the eye. Examples of ophthalmic compositions are suspensions, ointments, gels, sprays, creams, sustained release formulations and/or solutions suitable for application as an eye drop. In certain embodiments, the composition may be applied directly to a contact lens and/or otherwise be a contact lens care solution in which the contact lens is soaked, prior to being fitted to the subject's eye. Without being bound by any theory or particular mode of action, it is believed that that this would allow for the active to be absorbed into the matrix of the contact lens or coated onto or into the surface of the contact lens, then slowly released into or onto the treatment area, particularly the eyelid and/or upper tarsal conjunctiva, once fitted to the eye.

[0085] Aqueous solutions (including those released from soft contact lenses) are typically useful, based on ease of formulation, as well as a subject's ability to easily administer such compositions by means of instilling one to two drops of the solution in the affected eyes. In the case of contact lenses, the administration of the solution is simplified in that the contact lens and the solution are applied in the one step. However, the compositions may also be suspensions, viscous or semi-viscous gels, or other types of solid or semi-solid compositions such as ointments and creams. The ointments have the advantage that they are slowly absorbed and thus provide for sustained release.

[0086] In the case of a spray, the composition may be applied to the inside of the eyelid. The composition disclosed herein may also be applied as a solution whereby soft contact lenses, including silicone hydrogel lenses, may absorb the solution or coat the surface and then release it when fitted on the eye. The contact lens maintains the solution in contact with the eye-lid when the wearer blinks, as opposed to eye drops or a spray which may be relatively quickly drained off the eye by the normal tear action.

[0087] A variety of carriers may be used in the compositions disclosed herein including one or more of the following: water, mixtures of water and water-miscible solvents, such as C.sub.1- to C.sub.7-alkanols; vegetable oils or mineral oils comprising from 0.5 to 5% non-toxic water-soluble polymers; gelling products, such as gelatin, alginates, pectins, tragacanth, karaya gum, xanthan gum, carrageenan, agar and acacia, and their derivatives; starch derivatives, such as starch acetate and hydroxypropyl starch; cellulose and its derivatives and also other synthetic products, such as polyvinyl alcohol, polyvinylpyrrolidone, polyvinyl methyl ether, polyethylene oxide, cross-linked polyacrylic acid, such as neutral Carbopol, or, mixtures of those polymers; naturally-occurring phosphatide, for example, lecithin, or condensation products of an alkylene oxide with fatty acids, for example polyoxyethylene stearate, or condensation products of ethylene oxide with long chain aliphatic alcohols, for example heptadecaethyleneoxycetanol, or condensation products of ethylene oxide with partial esters derived from fatty acids and a hexitol such as polyoxyethylene sorbitol monooleate, or condensation products of ethylene oxide with partial esters derived from fatty acids and hexitol anhydrides, for example polyethylene sorbitan mono-oleate.

[0088] Dispersible powders and granules suitable for preparation of an aqueous suspension by the addition of water provide the active ingredient in admixture with a dispersing or wetting agent, suspending agent and one or more preservatives. Suitable dispersing or wetting agents and suspending agents are exemplified by those mentioned herein.

[0089] The composition according to the present invention may comprise at least one gelling agent. Gelling agents suitable for use in pharmaceutical compositions are known to those of ordinary skill in the art and include, for example one or more of the following: xanthan gum and its derivatives; carbomer and its derivatives; acrylate based copolymers and cross polymers; sodium polyacrylate and its derivatives; cellulose and its derivatives; and starch and agar and their derivatives.

[0090] In certain embodiments, the selection of the gelling agent may involve selecting a gelling agent that provides a clear gel, a substantially clear gel, or an acceptably clear gel. The amount of gelling agent added to the composition may be readily determined by one of ordinary skill in the art with a minimum of experimentation, and will depend upon factors known to those skilled in the art, such as the properties of the gelling agent and the desired properties of the composition.

[0091] Additional ingredients that may be included in the compositions of the invention include surfactant, anti-oxidants, tonicity enhancers, preservatives, stabilizers, non-toxic excipients, demulcents, sequestering agents, pH adjusting agents, co-solvents, viscosity building agents or combinations thereof.

[0092] For the adjustment of the pH, for example, to a physiological pH, buffers may be useful. The pH of the present solutions typically may be maintained within the range of between 6.5 to 8.0. Other ranges may also be used, for example, between 7.2 to 7.5, between 6.8 to 7.2 or between 7.3 to 7.5. Selecting a pH or pH range that is compatible, or substantially compatible, with the ocular surface is typically desired. Suitable buffers may be added, such as one or more of the following: boric acid; sodium borate; potassium citrate; citric acid; sodium bicarbonate; and TRIS, disodium edetate (EDTA) and various phosphate buffers (including combinations of NaCl, KCl, Na.sub.2HPO.sub.4, NaH.sub.2PO.sub.4 and KH.sub.2PO.sub.4) and mixtures thereof. In certain embodiments, the buffer used contains concentrations of about NaCl 8 g/L, KCl 0.2 g/L, Na.sub.2HPO.sub.41.15 g/L and KH.sub.2PO.sub.4 0.2 g/L.

[0093] Tonicity is adjusted if needed typically by tonicity enhancing agents. Such agents may, for example, be of ionic and/or non-ionic type. Examples of ionic tonicity enhancers are alkali metal or earth metal halides, such as, for example one or more of the following: CaCl.sub.2, KBr, KCl, LiCl, NaI, NaBr or NaCl, Na.sub.2SO.sub.4 and boric acid. Non-ionic tonicity enhancing agents are, for example, urea, glycerol, sorbitol, mannitol, propylene glycol, dextrose or combinations thereof. In certain embodiments, the aqueous solutions may be adjusted with tonicity agents to approximate the osmotic pressure of normal lachrymal fluids.

[0094] In certain embodiments, the compositions of the invention additionally comprise a preservative. A preservative may typically be selected from a quaternary ammonium compound such as benzalkonium chloride (N-benzyl-N(C.sub.8-C.sub.18-alkyl)-N,N-trimethylammonium chloride), benzoxonium chloride or the like. Examples of preservatives different from quaternary ammonium salts are alkyl-mercury salts of thiosalicylic acid, such as, for example, thiomersal, phenylmercuric nitrate, phenylmercuric acetate or phenylmercuric borate, sodium perborate, sodium chlorite, parabens, such as, for example, methylparaben or propylparaben, sodium benzoate, salicylic acid, alcohols, such as, for example, chlorobutanol, benzyl alcohol or phenyl ethanol, guanidine derivatives, such as, for example, chlorohexidine or polyhexamethylene biguanide, sodium perborate, Germal or sorbic acid. In certain embodiments, preservatives such quaternary ammonium compounds, in particular benzalkonium chloride or its derivative such as Polyquad, alkyl-mercury salts and parabens may be used. Other suitable preservatives include polymyxin B sulphate and Purite. Where appropriate, a sufficient amount of preservative is added to the ophthalmic composition to ensure protection against secondary contamination during use caused by bacteria and fungi. In certain embodiments, the compositions of this invention do not include a preservative, is are preservative free. Such formulations would be useful for subjects who wear contact lenses.

[0095] In certain embodiments, the compositions additionally may comprise a surfacant. A surfactant may typically be selected from but not limited to Sodium Lauryl Sulphate BP, Sorbitan esters: Spans, Sorbitan monooleate, Polyoxyethylene glycol sorbitan alkyl esters: Polysorbate Block copolymers of polyethylene glycol and polypropylene glycol: Poloxamers and the quaternary ammonium and pyridinium cationic surfactants.

[0096] In other embodiments, the compositions additionally may comprise an anti-oxidants. An anti-oxidant may typically be selected from but not limited to: glutathione, vitamin C, vitamin A, and vitamin E, ascorbic acid and tocopherols, gallates, Glucam E-20 Butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT).

[0097] The compositions disclosed herein may comprise further non-toxic excipients, such as, for example, emulsifiers, wetting agents or fillers, such as, for example, the polyethylene glycols designated 200, 300, 400 and 600, or Carbowax designated 1000, 1500, 4000, 6000 and 10000. The amount and type of excipient added is in accordance with the particular requirements.

[0098] Other compounds may also be added to the compositions of the present invention to increase the viscosity of the carrier. Examples of viscosity enhancing agents include, but are not limited to: polysaccharides, chondroitin sulfate and its salts, dextrans, various polymers of the cellulose family; vinyl polymers; acrylic acid polymers and/combinations thereof.

[0099] In certain embodiments, the composition may be administered in ways that are deemed suitable by a person of ordinary skill in the art. The composition may be administered topically or orally. The composition of the invention may be administered in single or multiple doses and for various length of times until the disease or condition is either completely treated or until the desired level of treatment has been achieved. The person of ordinary skill in the art will recognise that the dosage amount, dosage regimen and length of treatment may depend on factors such as, for example, the disease type, the location, the severity of the disease or disorder, need to alleviate symptoms and the health of the subject. In the case of a contact lens care solution, the composition may be administered once a day (when the contact lens is applied). Alternatively, the contact lens may be stored in the care solution (e.g. overnight) whilst not being worn by the subject. In the case of eye drops, the composition may be administered every two to four hours or more frequently for example every half hourly when subject has severe symptoms. In the case of ointment or cream, the composition may be administered every two to four hours. When administered orally, the composition may for example, be taken one to two times a day.

[0100] In certain embodiments, the ophthalmic device containing the C.sub.8 to C.sub.16 fatty acids and/or related fatty acid esters, for example, glycerol monolaurate and/or lauric acid, may be prepared by contacting the ophthalmic device with a solution containing the C.sub.8 to C.sub.16 fatty acids and/or related fatty acid esters. Where there is a combination of more than one fatty acid and/or fatty acid ester the ophthalmic device may be contacted with either one solution or a series of solutions containing one or more of the fatty acids or fatty acid esters. Similarly if the ophthalmic device additionally contains androgen or androgen analogue and/or an anti-inflammatory agent, the ophthalmic device may be contacted with a single solution containing or a series of solutions containing one or more of the fatty acids and/or fatty acid ester and androgen, androgen analogue and/or anti-inflammatory agent. The above actives may be contacted with the ophthalmic device prior to selling or delivering the ophthalmic device to a subject (e.g. adding the active(s) to one or more solutions prior to sealing the package, and subsequently sterilizing the package) or during the preparation of the ophthalmic device. Where one or more active ingredient is contacted to the ophthalmic device prior to selling or delivering the ophthalmic device, the other actives may be contacted to the ophthalmic device during preparation of the ophthalmic device. As discussed herein, in certain embodiments, one or more of the actives are incorporated into liposomes which are attached to the device (such as a lens) and which then permit the actives to be released during wearing of the device.

[0101] Sterilization can take place at different temperatures and periods of time. In certain embodiments, sterilization is carried out using filter sterilization.

[0102] The solutions that are used in one or more of the disclosed methods may be water-based (i.e. aqueous) solutions. Typical solutions include saline solutions, other buffered solutions, deionized water or combinations thereof. For example, an aqueous solution is deionized water or saline solution containing salts including sodium chloride, sodium borate, sodium phosphate, sodium hydrogen phosphate, sodium dihydrogenphosphate, the corresponding potassium salts of the same or combinations thereof. These ingredients are generally combined to form buffered solutions that include an acid and its conjugate base, so that addition of acids and bases cause a relatively small change in pH. The buffered solutions may additionally include 2-(N-morpholino)ethanesulfonic acid (MES), sodium hydroxide, 2,2-bis(hydroxymethyl)-2,2,2-nitrilotriethanol,n-tris(hydroxymethyl)methyl-2-aminoethanesulfonic acid, citric acid, sodium citrate, sodium carbonate, sodium bicarbonate, acetic acid, sodium acetate, ethylenediamine tetraacetic acid and the like and combinations thereof. For example, the solution is a borate buffered or phosphate buffered saline solution or deionized water. For example, the solution contains about NaCl 8 g/L, KCl 0.2 g/L, Na.sub.2HPO.sub.4 1.15 g/L and KH.sub.2PO.sub.4 0.2 g/L buffer.

[0103] The kit or article of manufacture may comprise a container and a label or package insert on or associated with the container. Suitable containers include, for example, bottles, vials, syringes, blister pack, tubes etc. The containers may be formed from a variety of materials such as metal, glass or plastic. The container holds the composition which is effective for treating the condition and may have a sterile access port (for example the container may be an intravenous solution bag or a vial having a stopper piercable by a hypodermic injection needle). The label or package insert indicates that the composition is used for treating the condition of choice. In certain embodiments, the label or package insert includes instructions for use and indicates that the therapeutic composition may be used to prevent, reduce and/or treat dry eye. Where the composition comprises C.sub.8 to C.sub.12 fatty acid and/or fatty acid ester, an additional container may comprise androgen or androgen analogue and/or an anti-inflammatory agent. Alternatively, the anti-inflammatory agent may be contained in a separate container.

[0104] The kit may comprise (a) a C.sub.8 to C.sub.16 fatty acid or fatty acid ester, a composition or contact lens care solution as described above; and (b) a second container comprising a solution that is suitable for application to the eye, carriers, excipients, and the like. The kit in this embodiment of the invention may further comprise one or more package inserts. The inserts, for example, indicate how the C.sub.8 to C.sub.16 fatty acid and/or fatty acid ester composition and the excipient may be used to prevent, reduce and/or treat dry eye, and provide instructions for use of the kit.

[0105] The second container may comprise a solution that is suitable for application to the eye (e.g. an aqueous solution) and/or pharmaceutically-acceptable buffers, such as bacteriostatic water for injection (BWFI), phosphate-buffered saline, Ringer's solution and dextrose solution. It may further include other materials desirable from a commercial and user standpoint, including other buffers, diluents, filters, needles, and syringes. It will be understood that the invention disclosed and defined in this specification extends to all alternative combinations of two or more of the individual features mentioned or evident from the text or drawings. All of these different combinations constitute various alternative aspects of the invention.

EXAMPLES

[0106] The present invention will now be more fully described with reference to the accompanying examples and drawings. It should be understood, however, that the description following is illustrative only and should not be taken in any way as a restriction on the generality of the invention described above.

Example 1

[0107] One aspect of this invention is inhibition of lipase activity without substantial antibacterial activity. This example illustrates one readily available assay for lipase activity and bacterial growth in certain conditions; especially concentration of active, time and bacterial species. In the following example, lipase activity and bacterial growth has been assayed in four different strains of bacteria following treatment with various concentrations of glycerol monolaurate or lauric acid.

[0108] The bacterial strains S. aureus 020 & 134, and S. epidermidis 024 & 025 were grown at 37 C. in TSB treated with 0, 6.25 or 12.5 g/ml of glycerol monolaurate or lauric acid as well as in TSB extraction of glycerol monolaurate ointment prior to assay of bacterial growth and lipase activity. After incubation for 24 h, bacterial growth was determined by measuring the optical density of cultures using a spectrophotometer at a wavelength of 660 nm. Lipase activity by test bacterial strains under various treatments were assessed by examining the lipase activity in bacterial culture supernatants with a QuantiChrom Lipase Assay Kit. The results of the experiment are presented in Tables 1-4 below. The data show that glycerol monolaurate inhibits lipase activity by approximately 16-88% (Table 1), lauric acid inhibits lipase activity by approximately 46-72% (Table 2), and extractions of glycerol monolaurate ointment of composition 14 (contents outlined below) inhibit lipase activity by approximately 51-77% (Tables 3 and 4), when used at concentrations that do not substantially inhibit growth of the bacterial strains.

TABLE-US-00001 TABLE 1 Glycerol monolaurate Inhibition of Strain (g/ml) Growth Lipase activity S. aureus 020 5 1% 16% 7.5 0 29% 10 4% 50% 12.5 4% 63% 15 2% 73% 17.5 0 88% S. aureus 134 10 0 25% 12.5 0 38% 15 1% 49% 17.5 0 63% S. epidermidis 024 6.25 0 46% 12.5 0 70% S. epidermidis 025 6.25 0 48% 12.5 0 72%

TABLE-US-00002 TABLE 2 Lauric acid Inhibition of Strain (g/ml) Growth Lipase activity S. epidermidis 024 6.25 0 46% 12.5 0 70% S. epidermidis 025 6.25 0 48% 12.5 0 72%

TABLE-US-00003 TABLE 3 Ointment Inhibition of Strain extraction in TSB Growth Lipase production S. aureus 020 GML0.01% + 0 71% TT0.02% GML0.025% + 0 77% TT0.02% * TTtestosterone, GMLGlycerol monolaurate, TSBTryptone Soy Broth

TABLE-US-00004 TABLE 4 Ointment Inhibition of Strain extraction in TSB Growth Lipase activity S. aureus 020 GML0.025% 4% 51% GML0.05% 2% 59% * GMLGlycerol monolaurate, TSBTryptone Soy Broth

Example 2

[0109] In this example, lipase and bacterial activity has been similarly assayed in five different strains of bacteria (S. epi001, S. epi024, S. epi025, S. aur020 and S. aur134). The bacterial strains were treated with 0, 3.125, 6.25, 12.5 or 25 g/ml of glycerol monolaurate or lauric acid and grown in TSB at 0.37 C. After incubation for 24 h, both bacterial growth and lipase production were determined. FIG. 1 shows the results of the bacterial growth assay for the strains treated with glycerol monolaurate. FIG. 2 the results of the bacterial growth assay for the strains treated with lauric acid. FIG. 3 shows the results of the lipase production assay for the strains treated with glycerol monolaurate. FIG. 4 shows the results of the lipase production assay for the strains treated with lauric acid. FIG. 5 shows the percentage reduction of lipase production for each test strain and treatment.

Example 3

[0110] The following tables provide several examples of compositions, according to certain embodiments. The compositions contain either glycerol monolaurate and/or caprylic acid and/or lauric acid and/or monocaprin with or without androgen, with or without an anti-inflammatory agent, buffer (NaOH/HCl) and a tonicity agent (sodium chloride). Compositions 1, 2 and 4 to 7 contain a preservative (chlorobutanol although benzalkonium chloride or alkyldimethylbenzylammonium chloride could also be used). Composition 3 and 8 is a preservative free preparation containing glycerol monolaurate and composition 9 is a preservative free preparation containing lauric acid. Composition 10 is a preservative free preparation containing glycerol monolaurate and androgen and composition 11 is a preservative free preparation containing lauric acid and androgen. Composition 12 is a preservative free preparation containing glycerol monolaurate and androgen and an anti-inflammatory agent. Composition 13 is a preservative free preparation containing lauric acid and androgen and an antiinflammatory agent. Composition 14 is an ointment formulation with glycerol monolaurate and composition 15 is an ointment formulation with lauric acid. Composition 16 is an ointment formulation with glycerol monolaurate and androgen and composition 17 is an ointment formulation with lauric acid and androgen. Composition 18 is an ointment formulation with glycerol monolaurate and androgen and anti-inflammatory agent and composition 19 is an ointment formulation with lauric acid and androgen and anti-inflammatory agent. Composition 20 is another example of an ointment formulation with glycerol monolaurate and androgen and anti-inflammatory agent. Composition 21 is another example of an ointment formulation with lauric acid and androgen and anti-inflammatory agent. Composition 22 is another example of an ointment formulation with glycerol monolaurate and androgen and anti-inflammatory agent in a different preservative. Composition 23 is another example of an ointment formulation with lauric acid and androgen and anti-inflammatory agent with a different preservative.

Composition 1: Topical Drops Containing Glycerol Monolaurate

[0111]

TABLE-US-00005 Ingredient Concentration (wt %) Glycerol monolaurate 0.005% Androgen .sup.1% Caprylic capric triglyceride .sup.5% Chlorobutanol 0.5% Sorbitan monooleate 0.5% Potassium dihydrogen orthophosphate 0.2% (KH.sub.2PO.sub.4) di-sodium hydrogen orthophosphate 1.15% (anhydrous Na.sub.2HPO.sub.4) Potassium chloride (KCl) 0.2% Sodium Chloride 0.8% pH 6-8 Purified water Quantity sufficient

Composition 2: Topical Drops Containing Lauric Acid

[0112]

TABLE-US-00006 Ingredient Concentration (wt %) Lauric acid 0.01% Androgen .sup.1% Caprylic capric triglyceride .sup.5% Chlorobutanol 0.5% Sorbitan monooleate 0.5% Potassium dihydrogen orthophosphate 0.2% (KH.sub.2PO.sub.4) di-sodium hydrogen orthophosphate 1.15% (anhydrous Na.sub.2HPO.sub.4) Potassium chloride (KCl) 0.2% Sodium Chloride 0.8% pH 6-8 Purified water Quantity sufficient

Composition 3: Unit Dose Preservative-Free Preparation

[0113]

TABLE-US-00007 Ingredient Concentration (wt %) Glycerol monolaurate etc 0.005% Caprylic capric triglyceride .sup.5% Sorbitan monooleate 0.5% Potassium dihydrogen orthophosphate 0.2% (KH.sub.2PO.sub.4) di-sodium hydrogen orthophosphate 1.15% (anhydrous Na.sub.2HPO.sub.4) Potassium chloride (KCl) 0.2% Sodium Chloride 0.8% pH 6-8 Purified water Quantity sufficient

Composition 4: Topical Drops Containing Glycerol Monolaurate

[0114]

TABLE-US-00008 Ingredient Concentration (%, w/v) Glycerol monolaurate 0.005% Testosterone 0.02% Chlorobutanol 0.3% Sorbitan monooleate 0.05% Potassium dihydrogen orthophosphate 0.2% (KH.sub.2PO.sub.4) di-sodium hydrogen orthophosphate 1.15% (anhydrous Na.sub.2HPO.sub.4) Potassium chloride (KCl) 0.2% Sodium Chloride 0.8% pH 6-8 Purified water Quantity sufficient

Composition 5: Topical Drops Containing Glycerol Monolaurate and Lauric Acid

[0115]

TABLE-US-00009 Ingredient Concentration (%, w/v) Glycerol monolaurate 0.005% Lauric acid 0.005% Testosterone 0.02% Chlorobutanol 0.3% Sorbitan monooleate 0.05% Potassium dihydrogen orthophosphate 0.2% (KH.sub.2PO.sub.4) di-sodium hydrogen orthophosphate 1.15% (anhydrous Na.sub.2HPO.sub.4) Potassium chloride (KCl) 0.2% Sodium Chloride 0.8% pH 6-8 Purified water Quantity sufficient

Composition 6: Topical Drops Containing Lauric Acid and Monocaprin

[0116]

TABLE-US-00010 Ingredient Concentration (%, w/v) Lauric acid 0.005% Monocaprin 0.005% Testosterone 0.02% Chlorobutanol 0.3% Sorbitan monooleate 0.05% Potassium dihydrogen orthophosphate 0.2% (KH.sub.2PO.sub.4) di-sodium hydrogen orthophosphate 1.15% (anhydrous Na.sub.2HPO.sub.4) Potassium chloride (KCl) 0.2% Sodium Chloride 0.8% pH 6-8 Purified water Quantity sufficient

Composition 7: Topical Drops Containing Lauric Acid

[0117]

TABLE-US-00011 Ingredient Concentration (%, w/v) Lauric acid 0.005% Testosterone 0.02% Chlorobutanol 0.3% Sorbitan monooleate 0.05% Potassium dihydrogen orthophosphate 0.2% (KH.sub.2PO.sub.4) di-sodium hydrogen orthophosphate 1.15% (anhydrous Na.sub.2HPO.sub.4) Potassium chloride (KCl) 0.2% Sodium Chloride 0.8% pH 6-8 Purified water Quantity sufficient

Composition 8: Unit Dose Preservative-Free Preparation Containing Glycerol Monolaurate

[0118]

TABLE-US-00012 Ingredient Concentration (%, w/v) Glycerol monolaurate 0.005% Caprylic capric triglyceride .sup.5% Sorbitan monooleate 0.05% Potassium dihydrogen orthophosphate 0.2% (KH.sub.2PO.sub.4) di-sodium hydrogen orthophosphate 1.15% (anhydrous Na.sub.2HPO.sub.4) Potassium chloride (KCl) 0.2% Sodium Chloride 0.8% pH 6-8 Purified water Quantity sufficient

Composition 9: Unit Dose Preservative-Free Preparation Containing Lauric Acid

[0119]

TABLE-US-00013 Ingredient Concentration (%, w/v) Lauric acid 0.005% Caprylic capric triglyceride 5% Sorbitan monooleate 0.05% Potassium dihydrogen orthophosphate 0.2% (KH.sub.2PO.sub.4) di-sodium hydrogen orthophosphate 1.15% (anhydrous Na.sub.2HPO.sub.4) Potassium chloride (KCl) 0.2% Sodium Chloride 0.8% pH 6-8 Purified water Quantity sufficient

Composition 10: Unit Dose Preservative-Free Preparation Containing Glycerol Monolaurate and Testosterone

[0120]

TABLE-US-00014 Ingredient Concentration (%, w/v) Glycerol monolaurate 0.005% Testosterone 0.02% Caprylic capric triglyceride 5% Sorbitan monooleate 0.05% Potassium dihydrogen orthophosphate 0.2% (KH.sub.2PO.sub.4) di-sodium hydrogen orthophosphate 1.15% (anhydrous Na.sub.2HPO.sub.4) Potassium chloride (KCl) 0.2% Sodium Chloride 0.8% pH 6-8 Purified water Quantity sufficient

Composition 11: Unit Dose Preservative-Free Preparation Containing Lauric Acid and Testosterone

[0121]

TABLE-US-00015 Ingredient Concentration (%, w/v) Lauric acid 0.005% Testosterone 0.02% Caprylic capric triglyceride 5% Sorbitan monooleate 0.05% Potassium dihydrogen orthophosphate 0.2% (KH.sub.2PO.sub.4) di-sodium hydrogen orthophosphate 1.15% (anhydrous Na.sub.2HPO.sub.4) Potassium chloride (KCl) 0.2% Sodium Chloride 0.8% pH 6-8 Purified water Quantity sufficient

Composition 12: Unit Dose Preservative-Free Preparation Containing Glycerol Monolaurate, Testosterone, and Anti-Inflammatory Agent

[0122]

TABLE-US-00016 Ingredient Concentration (%, w/v) Glycerol monolaurate 0.005% Testosterone 0.02% alpha-linolenic acid 0.2% Caprylic capric triglyceride 5% Sorbitan monooleate 0.05% Potassium dihydrogen orthophosphate 0.2% (KH.sub.2PO.sub.4) di-sodium hydrogen orthophosphate 1.15% (anhydrous Na.sub.2HPO.sub.4) Potassium chloride (KCl) 0.2% Sodium Chloride 0.8% pH 6-8 Purified water Quantity sufficient

Composition 13: Unit Dose Preservative-Free Preparation Containing Lauric Acid, Testosterone, and Anti-Inflammatory Agent

[0123]

TABLE-US-00017 Ingredient Concentration (%, w/v) Lauric acid 0.005% Testosterone 0.02% alpha-linolenic acid (Omega 3 fatty acids) 0.2% Caprylic capric triglyceride 5% Sorbitan monooleate 0.05% Potassium dihydrogen orthophosphate 0.2% (KH.sub.2PO.sub.4) di-sodium hydrogen orthophosphate 1.15% (anhydrous Na.sub.2HPO.sub.4) Potassium chloride (KCl) 0.2% Sodium Chloride 0.8% pH 6-8 Purified water Quantity sufficient

Composition 14: Topical Ointment Containing Glycerol Monolaurate

[0124]

TABLE-US-00018 Ingredient Concentration (%, w/w) Glycerol monolaurate 0.05% Sorbitan monooleate 0.05% Butylated Hydroxytolune 0.03% Olive oil 30% Ophthalmic ointment base Quantity sufficient (lanolin anhydrous 10%, mineral oil light 10%, petroleum white 80%)

Composition 15: Topical Ointment Containing Lauric Acid

[0125]

TABLE-US-00019 Ingredient Concentration (%, w/w) Lauric acid 0.05% Sorbitan monooleate 0.05% Butylated Hydroxytolune 0.03% Olive oil 30% Ophthalmic ointment base Quantity sufficient (lanolin anhydrous 10%, mineral oil light 10%, petroleum white 80%)

Composition 16: Topical Ointment Containing Glycerol Monolaurate and Testosterone

[0126]

TABLE-US-00020 Ingredient Concentration (%, w/w) Glycerol monolaurate 0.05% Testosterone 0.02% Sorbitan monooleate 0.05% Butylated Hydroxytolune 0.03% Olive oil 30% Ophthalmic ointment base Quantity sufficient (lanolin anhydrous 10%, mineral oil light 10%, petroleum white 80%)

Composition 17: Topical Ointment Containing Lauric Acid and Testosterone

[0127]

TABLE-US-00021 Ingredient Concentration (%, w/w) Lauric acid 0.05% Testosterone 0.02% Sorbitan monooleate 0.05% Butylated Hydroxytolune 0.03% Olive oil 30% Ophthalmic ointment base Quantity sufficient (lanolin anhydrous 10%, mineral oil light 10%, petroleum white 80%)

Composition 18: Topical Ointment Containing Glycerol Monolaurate, Testosterone and Anti-Inflammatory Agent

[0128]

TABLE-US-00022 Ingredient Concentration (%, w/w) Glycerol monolaurate 0.05% Testosterone 0.02% alpha-linolenic acid 0.2% Sorbitan monooleate 0.05% Butylated Hydroxytolune 0.03% Olive oil 30% Ophthalmic ointment base Quantity sufficient (lanolin anhydrous 10%, mineral oil light 10%, petroleum white 80%)

Composition 19: Topical Ointment Containing Lauric Acid, Testosterone and Anti-Inflammatory Agent

[0129]

TABLE-US-00023 Ingredient Concentration (%, w/w) Lauric acid 0.05% Testosterone 0.02% alpha-linolenic acid 0.2% Sorbitan monooleate 0.05% Butylated Hydroxytolune 0.03% Olive oil 30% Ophthalmic ointment base Quantity sufficient (lanolin anhydrous 10%, mineral oil light 10%, petroleum white 80%)

Composition 20: Topical Ointment Containing Glycerol Monolaurate

[0130]

TABLE-US-00024 Ingredient Concentration (%, w/w) Glycerol monolaurate 0.05% Testosterone 0.02% alpha-linolenic acid 0.2% Vit E 2.5% Olive oil 30% Ophthalmic ointment base Quantity sufficient (lanolin anhydrous 10%, mineral oil light 10%, petroleum white 80%)

Composition 21: Topical Ointment Containing Lauric Acid

[0131]

TABLE-US-00025 Ingredient Concentration (%, w/w) Lauric acid 0.05% Testosterone 0.02% alpha-linolenic acid 0.2% Vit E 2.5% Olive oil 30% Ophthalmic ointment base Quantity sufficient (lanolin anhydrous 10%, mineral oil light 10%, petroleum white 80%)

Composition 22: Topical Ointment Containing Glycerol Monolaurate

[0132]

TABLE-US-00026 Ingredient Concentration (%, w/w) Glycerol monolaurate 0.05% Testosterone 0.02% alpha-linolenic acid 0.2% Vit E 1% Caprylic capric triglyceride 5% Olive oil 25% Ophthalmic ointment base Quantity sufficient (lanolin anhydrous 10%, mineral oil light 10%, petroleum white 80%)

Composition 23: Topical Ointment Containing Lauric Acid

[0133]

TABLE-US-00027 Ingredient Concentration (%, w/w) Lauric acid 0.05% Testosterone 0.02% alpha-linolenic acid 0.2% Vit E 1% Caprylic capric triglyceride 5% Olive oil 25% Ophthalmic ointment base Quantity sufficient (lanolin anhydrous 10%, mineral oil light 10%, petroleum white 80%)

[0134] Other exemplary non-limiting embodiments are described in the numbered paragraphs below. Any reference to a numbered paragraph is reference to a paragraph within this section. [0135] 1. A method for treating a dry eye disorder in a subject by administering an amount of one or more fatty acids and/or fatty acid esters therapeutically effective to inhibit lipase activity without substantially altering the dynamic microbial community of the eye. [0136] 2. The method of paragraph 1 wherein the fatty acids and/or fatty acid esters are C.sub.8 to C.sub.16 fatty acids and/or fatty acid esters. [0137] 3. The method of paragraph 1 wherein the fatty acids and/or fatty acid esters are C.sub.10 to C.sub.14 fatty acids and/or fatty acid esters [0138] 4. The method of one or more of the proceeding paragraphs, wherein the fatty acids and/or fatty acid esters are one or more of the following fatty acids and/or fatty acid esters: C.sub.8, C.sub.10, C.sub.11, C.sub.12, C.sub.14, glycerol monolaurate, lauric acid, capric acid, caprylic acid, myristic acid or combinations thereof. [0139] 5. The method of one or more of the proceeding paragraphs, wherein the fatty acid and/or fatty acid ester is glycerol monolaurate, lauric acid or a combination thereof. [0140] 6. The method of one or more of the preceding paragraphs further comprising administering a therapeutically effective amount of androgen. [0141] 7. The method of paragraph 6, wherein the androgen is selected from one or more of the following: dehydroepiandrosterone (DHEA), androsterone, testosterone and dihydrotestosterone. [0142] 8. The method of one of or more of the preceding paragraphs further comprising administering a therapeutically effective amount of an anti-inflammatory agent. [0143] 9. The method of paragraph 8, wherein the anti-inflammatory agent is selected from one or more of the following: azithromycin, cyclosporine A, omega-3 fatty acids and transforming growth factor beta (TGF-). [0144] 10. The method of one of or more of the preceding paragraphs wherein the administration is topically to the eye. [0145] 11. The method of one of or more of the preceding paragraphs wherein the concentration of fatty acids and/or fatty acid esters is about 0.01 to 50 g/ml in the eye drops or associated with the contact lens. [0146] 12. The method of one of or more of the preceding paragraphs wherein the concentration of fatty acids and/or fatty acid esters is about 0.00001% to 0.005% by weight of the total volume of the eye drops. [0147] 13. The method of paragraph 10, wherein the topical administration is in the form of an ointment, cream, eye drops or released from an ophthalmic device. [0148] 14. The method of paragraph 12, wherein the ophthalmic device is a contact lens. [0149] 15. The method of one or more of the proceeding paragraphs, wherein the amount of glycerol monolaurate included in the eye drops or associated with the contact lenses is in a concentration of about 0.01 to 50 g/ml. [0150] 16. The method of one or more of proceeding paragraphs, wherein the amount of lauric acid included in the eye drops or associated with the contact lenses is in a concentration of about 0.01 to 50 g/ml. [0151] 17. The method of one or more of proceeding paragraphs, wherein the amount of the fatty acids and/or fatty acid eaters included in the ointment or the cream is in a concentration of about 0.005% to 0.05% weight of the total weight of the ointment or the cream. [0152] 18. The method of one or more of the proceeding paragraphs, wherein the amount of glycerol monolaurate included in the ointment or the cream is in a concentration of about 0.005% to 0.05% by weight of the total weight of the ointment or the cream. [0153] 19. The method of one or more of the proceeding paragraphs, wherein the amount of lauric acid included in the eye drops or associated with the contact lenses is in a concentration of about 2.5 to about 25 g/ml. [0154] 20. The methods of one or more of the proceeding paragraphs, wherein the administration is oral. [0155] 21. The method of one or more of the preceding paragraphs wherein the administration is to alleviate symptoms of a dry eye or for preventing the dry eye disorder in the subject. [0156] 22. A composition for treating a dry eye disorder in a subject, wherein the composition comprises an amount of one or more fatty acids and/or fatty acid esters therapeutically effective to inhibit lipase activity without substantially altering the dynamic microbial community of the eye. [0157] 23. A composition for treating a dry eye disorder in a subject, the composition comprising a therapeutically effective amount of: one or more fatty acids and/or fatty acid esters and an androgen, wherein the composition is effective to inhibit lipase activity without substantially altering the dynamic microbial community of the eye. [0158] 24. A composition for treating a dry eye disorder in a subject, the composition comprising a therapeutically effective amount of: one or more fatty acids and/or fatty acid esters; an androgen and an anti-inflammatory agent, wherein the composition is effective to inhibit lipase activity without substantially altering the dynamic microbial community of the eye. [0159] 25. A composition for treating a dry eye disorder in a subject, the composition comprising a therapeutically effective amount of: one or more fatty acids and/or fatty acid esters and an anti-inflammatory agent, wherein the composition is effective to inhibit lipase activity without substantially altering the dynamic microbial community of the eye. [0160] 26. A composition for treating a dry eye disorder in a subject, the composition comprising: one or more fatty acids and/or fatty acid esters and the concentration of one or more fatty acids and/or fatty acid esters in the composition is about 0.01 to about 50 g/ml; and an amount of androgen that is about 0.05% to about 3% by weight of the total weight of the composition, wherein the composition is effective to inhibit lipase activity without substantially altering the dynamic microbial community of the eye. [0161] 27. A composition for treating a dry eye disorder in a subject, the composition comprising: one or more fatty acids and/or fatty acid esters and the concentration of one or more fatty acids and/or fatty acid esters in the composition is about 2.5 to about 25 g/ml; an amount of androgen that is about 0.05% to about 3% by weight of the total weight of the composition and an anti-inflammatory agent that is about 0.001% to about 5% by weight of the total weight of the composition, wherein the composition is effective to inhibit lipase activity without substantially altering the dynamic microbial community of the eye. [0162] 28. A composition for treating a dry eye disorder in a subject, the composition comprising: one or more fatty acids and/or fatty acid esters and the concentration of one or more fatty acids and/or fatty acid esters in the composition is about 2.5 to about 25 g/ml and an anti-inflammatory agent that is about 0.001% to about 5% by weight of the total weight of the composition, wherein the composition is effective to inhibit lipase activity without substantially altering the dynamic microbial community of the eye. [0163] 29. A cream or ointment composition for treating a dry eye disorder in a subject, the composition comprising: one or more fatty adds and/or fatty acid esters that is about 0.005% to about 0.05% by weight of the total weight of the composition; and an amount of androgen that is about 0.05% to about 3% by weight of the total weight of the composition, wherein the composition is effective to inhibit lipase activity without substantially altering the dynamic microbial community of the eye. [0164] 30. A composition for treating a dry eye disorder in a subject, the composition comprising: one or more fatty acids and/or fatty acid esters and that is about 0.005% to about 0.05% by weight of the total weight of the composition; an amount of androgen that is about 0.05% to about 3% by weight of the total weight of the composition and an anti-inflammatory agent that is about 0.001% to about 5% by weight of the total weight of the composition, wherein the composition is effective to inhibit lipase activity without substantially altering the dynamic microbial community of the eye. [0165] 31. A composition for treating a dry eye disorder in a subject, the composition comprising: one or more fatty acids and/or fatty acid esters that is about 0.005% to about 0.05% by weight of the total weight of the composition; and an anti-inflammatory agent that is about 0.001% to about 5% by weight of the total weight of the composition, wherein the composition is effective to inhibit lipase activity without substantially altering the dynamic microbial community of the eye. [0166] 32. A composition according to one or more of the proceeding paragraphs further comprises a therapeutically effective amount of androgen. [0167] 33. A composition according to paragraph 32 wherein the androgen is selected from one or more of the following: dehydroepiandrosterone (DHEA), androsterone, testosterone and dihydrotestosterone. [0168] 34. A composition according to one or more of the proceeding paragraphs further comprises a therapeutically effective amount of an anti-inflammatory agent. [0169] 35. A composition according to paragraph 34 wherein the anti-inflammatory agent is selected from one or more of the following: azithromycin, cyclosporine A, omega-3 fatty acids and transforming growth factor beta (TGF-). [0170] 36. A composition according to one or more of the proceeding paragraphs, wherein the composition is suitable for topical administration to an eye. [0171] 37. The composition of one of or more of the preceding paragraphs wherein the concentration of fatty acids and/or fatty acid esters is about 0.01 to 50 g/ml in the eye drops or associated with the contact lens. [0172] 38. A composition according to one or more of the proceeding paragraphs, wherein the fatty acids and/or fatty acid esters are C.sub.8 to C.sub.16 fatty acids and/or fatty acid esters. [0173] 39. A composition according to one or more of the proceeding paragraphs, wherein the fatty acids and/or fatty acid esters are C.sub.10 to C.sub.14 fatty acids and/or fatty acid esters. [0174] 40. The composition of one or more of the proceeding paragraphs, wherein the fatty acids and/or fatty acid esters are one or more of the following fatty acids and/or fatty acid esters: C.sub.8, C.sub.10, C.sub.11, C.sub.12, C.sub.14, glycerol monolaurate, lauric acid, capric acid, caprylic acid, myristic acid or combinations thereof. [0175] 41. A composition according to one or more of the proceeding paragraphs, wherein the fatty acid and/or related fatty acid ester is glycerol monolaurate, lauric acid or a combination thereof. [0176] 42. A composition according to one or more of the proceeding paragraphs further comprises a therapeutically effective amount of androgen. [0177] 43. A composition according to paragraph 42 wherein the androgen is selected from one or more of the following: dehydroepiandrosterone (DHEA), androsterone, testosterone and dihydrotestosterone. [0178] 44. A composition according to one or more of the proceeding paragraphs further comprises a therapeutically effective amount of an anti-inflammatory agent. [0179] 45. A composition according to paragraph 44 wherein the anti-inflammatory agent is selected from one or more of the following: azithromycin, cyclosporine A, omega-3 fatty acids and transforming growth factor beta (TGF-). [0180] 46. A composition according to one or more of the proceeding paragraphs, wherein the composition is suitable for topical administration to an eye. [0181] 47. The composition of one of or more of the preceding paragraphs wherein the concentration of fatty acids and/or fatty acid esters is about 0.01 to 50 g/ml in the eye drops or associated with the contact lens. [0182] 48. The composition of one of or more of the preceding paragraphs wherein the concentration of fatty acids and/or fatty acid esters is about 0.00001% to 0.005% by weight of the total volume of the eye drops. [0183] 49. A composition according to paragraph 46 wherein the topical administration is in the form of an ointment, cream, eye drops or released from an ophthalmic device. [0184] 50. A composition according to paragraph 49 wherein the ophthalmic device is a contact lens. [0185] 51. A composition according to one or more of the above composition paragraphs, wherein the amount of glycerol monolaurate included in eye drops or associate with the contact lenses is in a concentration of about 0.01 to 50 g/ml. [0186] 52. A composition according to one or more of the proceeding paragraphs, wherein the amount of lauric acid included in eye drops or associated with the contact lenses is in a concentration of about 0.01 to 50 g/ml. [0187] 53. A composition according to one or more of proceeding paragraphs, wherein the amount of the fatty acids and/or fatty acid esters included in the ointment or the cream is in a concentration of about 0.005% to 0.05% weight of the total weight of the ointment or the cream. [0188] 54. A composition according to one or more of the above composition claims, wherein the composition is suitable for oral administration. [0189] 55. A composition for use in a method of treating a dry eye disorder wherein the method comprises administering the composition to a subject, wherein the composition comprises an amount of one or more fatty acids or fatty acid esters therapeutically effective to inhibit lipase activity without substantially altering the dynamic microbial community of the eye. [0190] 56. The composition for use in the method of one or more of the preceding claims, wherein the method further comprises administering a therapeutically effective amount of androgen and/or a therapeutically effective amount of an anti-inflammatory agent. [0191] 57. The composition for use in the method of one or more of the preceding claims wherein the eye disorder is dry eye. [0192] 58. The composition for use in the method of one or more of the preceding claims wherein the method comprises administering the glycerol monolaurate and lauric acid in the form of eye drops or released from a contact lens.

[0193] Additionally, the disclosure has been described with reference to particular embodiments. However, it may be readily apparent to those skilled in the art that it is possible to embody the disclosure in specific forms other than those of the embodiments described above. The embodiments are merely illustrative and should not be considered restrictive.