WO2025165681A1 - Serum compositions with additive for ocular delivery in animals - Google Patents

Abstract

A composition for topical ophthalmic delivery in companion animals can include a blood-derived serum and an additive. The additive can include at least one of an antibiotic, an antihistamine, a vitamin, or a lysed white blood cell product.

Description

SERUM COMPOSITIONS WITH ADDITIVE FOR OCULAR

DELIVERY IN ANIMALS

RELATED APPLICATIONS

[0001] This application claims the benefit of U.S. Provisional Application No. 63/627,205 filed on 31 January 2024, now pending (hereinafter the ’205 Application). The contents of the priority application (z.e., the ’205 Application) are incorporated herein by reference in their entirety.

FIELD

[0002] The present disclosure relates generally to compositions for ocular delivery in animals, including methods of manufacture and apparatuses for preparing the same.

BACKGROUND

[0003] In the veterinary field, serum-based lubricants are known to effectively mitigate corneal degradation and ulcer development, while also tending to stabilize the cornea scaffolding. Additionally, serum-based lubricant products can be beneficial for certain other conditions, such as indolent ulcers, corneal trauma, allergic conjunctivitis, KCS (dry eye), and post-operative care.

[0004] The foregoing serum-based lubricants, however, are limited in their application of a wider variety of ocular conditions. In addition, serum-based lubricants (and especially autologous serums) are typically time intensive — and expensive — to make on an individual animal patient basis. Transmission of species-specific diseases and conditions is also a risk with allogeneic serums from presumed healthy donors. For these or other reasons, many veterinarians use over-the-counter eye drop solutions that are reasonably effective, but substantially less effective than their serum counterpart solutions. Accordingly, there is a constant need for serum-based solutions that can be combined with other therapeutic elements and made readily available for consumers in a cost-effective manner.

[0005] The subject matter claimed herein is not limited to examples that solve any disadvantages or that operate only in environments such as those described above. Rather, this background is only provided to illustrate one example technology area where some examples described herein may be practiced.

SUMMARY

[0006] An aspect of the present disclosure relates to a composition for topical ophthalmic delivery in companion animals. The composition can include a blood-derived serum and an antibiotic. In some examples, the antibiotic comprises an active ingredient from the fluoroquinolone family. In some examples, the antibiotic comprises an active ingredient that includes ciprofloxacin or levofloxacin. In one example, the composition includes a ratio of the blood-derived serum relative to the antibiotic that is between about 2 to 1 (2: 1) to about 10 to 1 (10: 1). In certain implementations, the blood-derived serum comprises bovine serum.

[0007] Another aspect of the present disclosure relates to a composition for topical ophthalmic delivery in companion animals in which the composition includes a blood-derived serum and an eye lubricant. In particular examples, the eye lubricant can include sodium hyaluronate. In some examples, the eye lubricant can include hyaluronic acid. In at least one example, the composition includes a ratio of the blood-derived serum relative to the eye lubricant that is between about 2 to 1 (2: 1) to about 10 to 1 (10: 1). In one example, the blood- derived serum can include bovine serum.

[0008] Yet another aspect of the present disclosure relates to a composition for topical ophthalmic delivery in companion animals in which the composition includes a blood-derived serum and an antihistamine. In some examples, the antihistamine can include pheniramine maleate. In particular examples, the composition includes a ratio of the blood-derived serum relative to the eye lubricant that is between about 2 to 1 (2: 1) to about 10 to 1 (10:1). In one example, the blood-derived serum can include bovine serum.

[0009] One aspect of the present disclosure relates to a composition for topical ophthalmic delivery in companion animals in which the composition includes a blood-derived serum and a vitamin. In some examples, the vitamin includes vitamin Bl. In particular examples, the composition includes a ratio of the blood-derived serum relative to the vitamin that is between about 2 to 1 (2: 1) to about 10 to 1 (10: 1). In one example, the blood-derived serum can include bovine serum.

[0010] Another aspect of the present disclosure relates to a composition for topical ophthalmic delivery in companion animals in which the composition includes a blood-derived serum and a lysed white blood cell product. In particular examples, the lysed white blood cell product includes a protein derived from the lysed white blood cell. In one example, the blood- derived serum can include bovine serum.

[0011] Yet another aspect of the present disclosure relates to a composition for topical ophthalmic delivery in companion animals in which the composition includes a blood-derived serum and an additive. The additive can include at least one of an antibiotic, an antihistamine, a vitamin, or a lysed white blood cell product.

[0012] Additional aspects of the present disclosure include a method of manufacturing any and all compositions described, referred to, exemplified, or shown. In particular examples, the method of manufacture includes one or more steps for mixing, product separation, storage, or packaging.

[0013] Other aspects of the present disclosure include an apparatus for manufacturing any and all compositions described, referred to, exemplified, or shown. In particular examples, the apparatus is configured to perform one or more steps of mixing, product separation, storage, or packaging.

BRIEF DESCRIPTION OF THE DRAWINGS

[0014] The disclosure will be readily understood by the following detailed description in conjunction with the accompanying drawings, wherein like reference numerals designate like structural elements, and in which:

[0015] FIG. 1 illustrates example raw materials for preparing and packaging at least a portion of one or more compositions of the present disclosure;

[0016] FIG. 2 illustrates an example fill station for preparing and packaging at least a portion of one or more compositions of the present disclosure;

[0017] FIG. 3 illustrates additional example raw materials for preparing and packaging at least a portion of one or more compositions of the present disclosure;

[0018] FIG. 4 illustrates an example eye dropper bottle being filled with an example composition (or a portion thereof) according to one or more examples of the present disclosure; and

[0019] FIG. 5 illustrates an example package including multiple eye dropper bottles filled with an example composition (or a portion thereof) according to one or more examples of the present disclosure.

DETAILED DESCRIPTION

[0020] Reference will now be made in detail to representative examples illustrated in the accompanying drawings. It should be understood that the following descriptions are not intended to limit the examples to one preferred example. To the contrary, it is intended to cover alternatives, modifications, and equivalents as can be included within the spirit and scope of the described examples as defined by the appended claims. [0021] The following disclosure relates to an eye drop solution for veterinarian use in companion animals, such as dogs, cats, and horses. The term companion animals should be interpreted as non-food chain animals that are not typically used for human consumption. The eye drop solution can include a blood-derived serum and an additive. A blood-derived serum can refer to the fluid and solvent component of blood that does not play a role in clotting. In other terms, blood-derived serum can be defined as blood plasma without the clotting factors (or plasma without fibrinogen). Serum can, in particular, include plasma proteins, electrolytes, and immunoglobulins. In certain examples, the blood-derived serum includes bovine serum (e.g., to impart a compatible cross-species advantage over typical autologous or allogeneic serums). By using bovine serum, for instance, transmission of species specific diseases or conditions can be mitigated.

[0022] Additionally, various additives can be implemented with the blood-derived serum. At least one of the additive or the blood-derived serum can constitute an active ingredient of a composition set forth in the present disclosure. An active ingredient can refer to an agent or a mixture of agents that causes a desired therapeutic effect.

[0023] In some examples a therapeutic effect can be an ameliorating effect that includes any therapeutically beneficial result in the treatment of a condition. For instance, an ameliorating effect can include a lessening in the severity or progression of a condition, remission, or a cure thereof.

[0024] In certain examples, a therapeutic effect can be a preventative effect or a prophylactic effect. The term “preventing” is art-recognized to include administration of a pharmaceutical or other remedy which reduces the frequency of, or delays the onset of, symptoms of a medical condition in a subject relative to a subject which does not receive the composition.

[0025] In some cases, compositions of the present disclosure can also be implemented as an adjunctive or add-on treatment. Such treatment can include any treatment given to bolster or enhance the effectiveness of a previous treatment, in particular in cases where the first treatment proved not to be fully effective. Likewise, an adjunctive or add-on treatment can include treatment given to bolster or enhance the effectiveness of a different treatment or drug (e.g., in a combined treatment).

[0026] A person of ordinary skill in the art will appreciate that compositions of the present disclosure can be administered with a “therapeutically effective dose” or “effective amount,” which terms mean a dose or amount that produces the desired effect for which it is administered. The exact dose or amount will depend on the purpose of the treatment.

[0027] As mentioned, the compositions of the present disclosure can include various additives. In some examples, an additive includes an antibiotic. In other examples, the additive includes an antihistamine. Yet another example of an additive includes a vitamin. In certain examples, the additive can include an eye lubricant. Furthermore, other examples of an additive include a lysed white blood cell product.

[0028] The present disclosure also relates to one or more methods of manufacturing a composition as disclosed herein. The present disclosure also relates to one or more apparatuses used to manufacture a composition as disclosed herein.

[0029] At least a portion of these or other examples are discussed below with reference to FIGS. 1-5. However, a person of ordinary skill in the art will readily appreciate that the detailed description given herein with respect to these figures is for explanatory purposes only and should not be construed as limiting. Furthermore, as used herein, a system, a method, an article, a component, a feature, or a sub-feature including at least one of a first option, a second option, or a third option should be understood as referring to a system, a method, an article, a component, a feature, or a sub-feature that can include one of each listed option (e.g., only one of the first option, only one of the second option, or only one of the third option), multiple of a single listed option (e.g., two or more of the first option), two options simultaneously (e.g., one of the first option and one of the second option), or combination thereof e.g., two of the first option and one of the second option).

[0030] FIG. 1 illustrates raw materials 100 for preparing and packaging at least a portion of one or more compositions of the present disclosure, according to one example. As shown, the raw materials 100 can include a blood-derived serum 102, a container 104, and a funnel 106. In some examples, the blood-derived serum 102 can include serum obtained from one or more donors. Such donors can be various species of donors, including cattle. In certain implementations, the blood-derived serum 102 is unfiltered serum.

[0031] The blood-derived serum 102 can be poured into the container 104. In some examples, the pouring process can include using the funnel 106 to guide the blood-derived serum 102 into the container 104.

[0032] Any of the features, components, and/or parts, including the arrangements and configurations thereof shown in FIG. 1 can be included, either alone or in any combination, in any of the other examples of devices, features, components, and parts shown in the other figures described herein. Likewise, any of the features, components, and/or parts, including the arrangements and configurations thereof shown and described with reference to the other FIGS, can be included, either alone or in any combination, in the example of the devices, features, components, and parts shown in FIG. 1.

[0033] FIG. 2 illustrates an example fill station 200 for preparing and packaging at least a portion of one or more compositions of the present disclosure. As shown, the fill station 200 can include the container 104 filled with the blood-derived serum 102. In addition, the fill station 200 can include a dispenser 202 that can attach (e.g, threadably attach) to the container

104. Various types of dispensers can be utilized. In some examples, the dispenser 202 includes a pump. In particular examples, the dispenser 202 includes calibrated dispensers that can dispense specific, predetermined volume amounts of the blood-derived serum 102. The predetermined volume amount to dispense can be adjusted as desired.

[0034] Any of the features, components, and/or parts, including the arrangements and configurations thereof shown in FIG. 2 can be included, either alone or in any combination, in any of the other examples of devices, features, components, and parts shown in the other figures described herein. Likewise, any of the features, components, and/or parts, including the arrangements and configurations thereof shown and described with reference to the other FIGS, can be included, either alone or in any combination, in the example of the devices, features, components, and parts shown in FIG. 2.

[0035] FIG. 3 illustrates additional example raw materials 300 for preparing and packaging at least a portion of one or more compositions of the present disclosure. As shown, the additional example raw materials 300 can include caps 302, nozzles 304, and bottles 306. The bottles 306 can include a variety of different shapes, sizes, and volumes. In particular implementations, the bottles 306 can range from about 2 ml size bottles to about 100 ml size bottles, about 5 ml size bottles to about 50 ml size bottles, or about 10 ml size bottles to about 30 ml size bottles.

[0036] The nozzles 304 can be inserted over an opening defined by a top portion of the bottles 306. Various size (or flow rate) of nozzles can be utilized. In some examples, the nozzles are about 0.01 ml dropper nozzles to about 1 ml dropper nozzles, about 0.02 ml dropper nozzles to about 0.5 ml dropper nozzles, or about 0.03 ml dropper nozzles to about 0.05 ml dropper nozzles.

[0037] The caps 302 can attach to the bottles 306 in a position that at least partially covers or surrounds the nozzles 304. In particular, the caps 302 can be snap fit, threadably engaged with, or otherwise removable attached to the bottles 306. [0038] Any of the features, components, and/or parts, including the arrangements and configurations thereof shown in FIG. 3 can be included, either alone or in any combination, in any of the other examples of devices, features, components, and parts shown in the other figures described herein. Likewise, any of the features, components, and/or parts, including the arrangements and configurations thereof shown and described with reference to the other FIGS, can be included, either alone or in any combination, in the example of the devices, features, components, and parts shown in FIG. 3.

[0039] FIG. 4 illustrates an example eye dropper bottle being filled with an example composition (or a portion thereof) according to one or more examples of the present disclosure. As shown, the blood-derived serum 102 is being dispensed into the bottle 306 via the dispenser 202. The dispenser 202 (and/or a user) can fill the bottle 306 with the blood-derived serum 102 up to a specified volume amount.

[0040] Any of the features, components, and/or parts, including the arrangements and configurations thereof shown in FIG. 4 can be included, either alone or in any combination, in any of the other examples of devices, features, components, and parts shown in the other figures described herein. Likewise, any of the features, components, and/or parts, including the arrangements and configurations thereof shown and described with reference to the other FIGS, can be included, either alone or in any combination, in the example of the devices, features, components, and parts shown in FIG. 4.

[0041] FIG. 5 illustrates an example package 500 including multiple eye dropper bottles 502 assembled and filled with an example composition (or a portion thereof) according to one or more examples of the present disclosure. The eye dropper bottles 502 can include the constituent components described above in relation to the foregoing figures.

[0042] The package 500 can include various materials, sizes, shapes, and configurations of packaging. As shown, the package 500 can include a cardboard box configuration with rows and columns of the eye dropper bottles 502. In particular examples, the package 500 can include separate storage spaces for individually housing (and protecting) the eye dropper bottles 502. The package 500 can be conveniently shipped and/or stored (e.g., frozen or refrigerated) as an individual box or in bulk.

[0043] Any of the features, components, and/or parts, including the arrangements and configurations thereof shown in FIG. 5 can be included, either alone or in any combination, in any of the other examples of devices, features, components, and parts shown in the other figures described herein. Likewise, any of the features, components, and/or parts, including the arrangements and configurations thereof shown and described with reference to the other FIGS, can be included, either alone or in any combination, in the example of the devices, features, components, and parts shown in FIG. 5.

[0044] It will be appreciated that the foregoing components, processes, and apparatuses described above in relation to FIGS. 1-5 can be modified for different methods and implementations. The processes, in particular, are merely illustrative, and alternative embodiments may omit, add to, reorder, and/or modify any aspect of the process flow shown, described, related to, or inferred by FIGS. 1-5. For instance, various aspects described above can be machine operated or robotically operated. Additionally or alternatively, various aspects described above can be implemented as part of an assembly line, conveyor system, or other automated/semi-automated system. In specific implementations, various aspects described above can be performed in one or more batches, or else performed according to various manufacturing methods (e.g., FIFO or first in, first out manufacturing).

[0045] The foregoing components, processes, and apparatuses described above in relation to FIGS. 1-5 can also be adapted for combining one or more additives to a serum to achieve a novel composition. In one example, an additive of the present disclosure includes an antibiotic. The antibiotic can include an antimicrobial substance active in fighting (e.g., killing or inhibiting growth of) bacteria. Some examples of an antibiotic can include oxytetracycline, clindamycin, polymyxin, neomycin, gramicidin, tobramycin, gentamicin sulfate, bacitracin, fluoroquinolones (e.g., ciprofloxacin, levofloxacin, moxifloxacin, ofloxacin, gemifloxacin, and delafloxacin), etc.

[0046] In these or other examples, a blood-derived serum combined with an antibiotic can treat infections while also providing eye lubrication. Some example bacterial infections that can be treated by the disclosed blood-derived serum combined with an antibiotic include blepharitis, corneal ulcers, pink eye, keratitis, conjunctivitis, other A. aerogenes, Rickettsiae, E. coli, and streptococci. Various dosages or potencies can be implemented and at various different time intervals. As used herein, the term potency refers to a measure of biological activity expressed in terms of a dose (e.g., a recommended dose, a suggested dose, a required dose, a minimum dose, or a maximum dose) to produce a pharmacological effect of a given intensity. In specific examples, a potency can refer to a quantitative potency value relative to a carrier substance, medium, or formulation. To illustrate, example potencies of the antibiotic can include about 0.1% to about 1% antibiotic, about 0.2% to about 0.5% antibiotic, or about 0.3% antibiotic.

[0047] These or other potencies of the antibiotic (including an associated carrier substance, medium, or formulation — as applicable) can be added in many different ratios relative to a blood-derived serum to form a combined antibiotic-blood derived serum composition. Some example ratios of the antibiotic relative to a blood-derived serum (when combined and formed into a composition) can include about 1 part antibiotic to about 1 part blood-derived serum (hereafter expressed in the form “X: Y”), about 1 :2 to about 1 : 10, about 1 :3 to about 1 :8, about 1 :4 to about 1 :6, about 2:1 to about 10: 1, about 3: 1 to about 8:1, or about 4: 1 to about 6: 1.

[0048] Further, in some implementations, the antibiotic can be released (e.g, into the bloodstream of the animal and/or local ocular tissue of the animal) within a predetermined time interval, such as within about five seconds to about five hours, about thirty seconds to about five hours, about fifteen minutes to about five hours, about twenty-five minutes to about four hours, about thirty minutes to about three hours, about sixty minutes to about two hours, or about one hour.

[0049] In another example, an additive includes an antihistamine. An antihistamine can include a drug class that targets histamine receptors (e.g., as a receptor antagonist or inverse agonist) of an animal. Some examples of an antihistamine can include diphenhydramine, loratadine, chlorphenamine, cinnarizine, hydroxyzine, promethazine, acrivastine, cetirizine, fexofenadine, pyrilamine maleate, pheniramine maleate, tripelennamine, etc.

[0050] In these or other examples, a blood-derived serum combined with an antihistamine can treat allergic reactions, cold symptoms, motion sickness, and/or vomiting. Various dosages or potencies can be implemented and at various different time intervals. Example potencies of the antihistamine can include about 0.1% to about 1% antihistamine, about 0.2% to about 0.5% antihistamine, or about 0.3% antihistamine.

[0051] These or other potencies of the antihistamine (including an associated carrier substance, medium, or formulation — as applicable) can be added in many different ratios relative to a blood-derived serum to form a combined antihistamine-blood derived serum composition. Some example ratios of the antihistamine relative to a blood-derived serum (when combined and formed into a composition) can include about 1 part antihistamine to about 1 part blood-derived serum (hereafter expressed in the form “X:Y”), about 1 :2 to about 1 : 10, about 1 :3 to about 1 :8, about 1 :4 to about 1 :6, about 2: 1 to about 10: 1, about 3: 1 to about 8: 1, or about 4: 1 to about 6: 1.

[0052] Further, in some implementations, the antihistamine can be released (e.g., into the bloodstream or local ocular tissue of the animal) within a predetermined time interval, such as within about five seconds to about five hours, about thirty seconds to about five hours, about fifteen minutes to about five hours, about twenty -five minutes to about four hours, about thirty minutes to about three hours, about sixty minutes to about two hours, or about one hour.

[0053] In some examples, an additive can include an eye lubricant. An eye lubricant can include a substance that cushions, moistens, hydrates, or soothes eyes. An eye lubricant can also be osmoprotectant and/or bioprotectant (e.g., to help stabilize ocular cells and/or maintain or restore the tear film). Some examples of an eye lubricant can include hyaluronic acid, sodium hyaluronate, viscoadaptive hyaluronan, viscoadaptive biopolymers, etc.

[0054] In these or other examples, a blood-derived serum combined with an eye lubricant can treat acute or seasonal dry eyes. Various dosages or potencies can be implemented and at various different time intervals. Example potencies of an eye lubricant (e.g., hyaluronic acid) can include about 0.1% to about 1% eye lubricant, about 0.2 % to about 0.5 % eye lubricant, or about 0.25% eye lubricant.

[0055] These or other potencies of the eye lubricant (including an associated carrier substance, medium, or formulation — as applicable) can be added in many different ratios relative to a blood-derived serum to form a combined eye lubricant-blood derived serum composition. Some example ratios of the eye lubricant relative to a blood-derived serum (when combined and formed into a composition) can include about 1 part eye lubricant to about 1 part blood-derived serum (hereafter expressed in the form “X:Y”), about 1 :2 to about 1 : 10, about 1 :3 to about 1 :8, about 1 :4 to about 1:6, about 2: 1 to about 10: 1, about 3 : 1 to about 8: 1, or about 4: 1 to about 6: 1.

[0056] Further, in some implementations, the eye lubricant can be released or activated in the eye within a predetermined time interval, such as within about one second to about five hours, about thirty seconds to about five hours, about fifteen minutes to about five hours, about twenty-five minutes to about four hours, about thirty minutes to about three hours, about sixty minutes to about two hours, or about one hour. [0057] In yet another example, an additive can include a vitamin, mineral, protein, amino acid, fats and fatty acids, and/or a supplement. A vitamin can include a variety of essential nutrients and organic substances that an animal can use or produce to live. Vitamins can be either fat soluble or water soluble. Examples of vitamins can include vitamin A, B vitamins (including Thiamin or vitamin Bl), vitamin C, vitamin D, vitamin E, vitamin K, choline, etc. Examples of a mineral can include magnesium, potassium, sulphur, sodium phosphorous, calcium, chloride, iron, zinc, copper, selenium, iodine, chromium, fluorine, cobalt, molybdenum, boron, and manganese. Examples of a protein can include casein, whey, and collagen. Examples of an amino acid can include arginine, histidine, isoleucine, leucine, lysine, methionine, cysteine, phenylalanine, threonine, tryptophan, valine, taurine, etc. Examples of fats and fatty acids can include linoleic acid, arachidonic acid, alpha-linoleic acid, eicosapentaenoic acid, and docosahexaenoic acid. Examples of a supplement can include antioxidants, fish oil, organ meat, glucosamine, probiotics, etc.

[0058] In these or other examples, a blood-derived serum combined with a vitamin (or other element mentioned above) can treat and/or prevent a host of different diseases and conditions. Various dosages or potencies can be implemented and at various different time intervals. Example potencies of a vitamin can vary by vitamin, animal species, breed, and/or weight (e.g., for thiamine administered to canines, about 0.5mg to about Img per pound about every twenty- four fours).

[0059] These or other potencies of the vitamin (including an associated carrier substance, medium, or formulation — as applicable) can be added in many different ratios relative to a blood-derived serum to form a combined vitamin-blood derived serum composition. Some example ratios of the vitamin relative to a blood-derived serum (when combined and formed into a composition) can include about 1 part vitamin to about 1 part blood-derived serum (hereafter expressed in the form “X:Y”), about 1 :2 to about 1 : 10, about 1 :3 to about 1 :8, about 1 :4 to about 1 :6, about 2:1 to about 10: 1, about 3: 1 to about 8:1, or about 4: 1 to about 6: 1.

[0060] Further, in some implementations, the vitamin can be released (e.g., into the bloodstream or local ocular tissue of the animal) within a predetermined time interval, such as within about one second to about five hours, about thirty seconds to about five hours, about fifteen minutes to about five hours, about twenty -five minutes to about four hours, about thirty minutes to about three hours, about sixty minutes to about two hours, or about one hour.

[0061] In a further example, an additive includes a lysed white blood cell product. The term “lysed cell” refers to a burst or ruptured cell. In some examples, a lysed cell can leave behind one or more products of interest. Accordingly, a lysed white blood cell product can include one or more elements extracted from the lysing process. In particular implementations, a lysed white blood cell product can include proteins. As examples, protein products from lysed white blood cells can include antibody proteins. Some specific examples of protein products from lysed white blood cells can include Myeloperoxidase, bactericidal/permeability-increasing protein (BPI), defensins, and the serine proteases neutrophil elastase, Proteinase 3 and cathepsin G, Alkaline phosphatase, lysozyme, NADPH oxidase, collagenase, lactoferrin, histaminase, cathelicidin, Cathepsin, gelatinase, collagenase, IL-IRA, Alpha 2-M, and sTNF.

[0062] White blood cells can be lysed in a variety of ways (e.g., upon separating the white blood cells from other blood components). In some examples, the lysis method can include mechanical approaches (e.g., utilizing a wareing blender polytron with rotating blades that can grind and disperse cells). In another example, the lysis method can include liquid homogenization (e.g., utilizing a Dounce homogenizer, a Potter-Elvehjem homegenizer, a French press, etc.) in which cell or tissue suspensions are sheared by forcing them through a narrow space. Yet another example lysis method can include sonication (e.g., utilizing a sonicator) that can implement high frequency sound waves to shear cells. Still another example lysis method can include freeze-thaw methods (e.g., utilizing a free or dry ice with ethanol) in which repeated cycles of freezing and thawing disrupt cells through ice crystal formation. Further, another example lysis method can include manual grinding methods (e.g., utilizing mortar and pestle) that involve grinding tissue that is frozen in liquid nitrogen. In some examples, a lysis method can include detergent-based methods that utilize particular types and concentrations of detergents, buffers, salts and reducing agents to provide results for particular species and types of cells. Enzymatic digestion and osmotic shock are additional examples of lysis methods.

[0063] In these or other examples, a blood-derived serum combined with a lysed white blood cell product can treat various conditions and/or generally stimulate the immune system of an animal. Various dosages or potencies can be implemented and at various different time intervals. Example potencies of a lysed white blood cell product can range from about 0.001% to about 5%, about 0.01% to about 1%, about 0.1% to about 0.5%, or about 0.3%.

[0064] These or other potencies of the lysed white blood cell product (including an associated carrier substance, medium, or formulation — as applicable) can be added in many different ratios relative to a blood-derived serum to form a combined lysed white blood cell product-blood derived serum composition. Some example ratios of the lysed white blood cell product relative to a blood-derived serum (when combined and formed into a composition) can include about 1 part lysed white blood cell product to about 1 part blood-derived serum (hereafter expressed in the form “X: Y”), about 1 :2 to about 1 : 10, about 1 :3 to about 1 :8, about 1 :4 to about 1 :6, about 2:1 to about 10: 1, about 3: 1 to about 8:1, or about 4: 1 to about 6: 1.

[0065] Further, in some implementations, the lysed white blood cell product can be released (e.g., into the bloodstream or local ocular tissue of the animal) within a predetermined time interval, such as within about one second to about five hours, about thirty seconds to about five hours, about fifteen minutes to about five hours, about twenty-five minutes to about four hours, about thirty minutes to about three hours, about sixty minutes to about two hours, or about one hour.

[0066] In particular implementations, an additive can include a combination of the foregoing examples. Furthermore, additional or alternative additives are herein contemplated. For instance, an additive can include homeopathic remedies, herbal remedies, corticosteroids, glucocorticoids, nonsteroidal anti-inflammatory drugs, pain reliever drugs, anticholinergics, analgesic, pH balancers, ocular hypertension drugs, glaucoma drugs, carbonic anhydrase inhibitors, beta blockers, antioxidants, immunosuppressive drugs, etc. In some examples, an additive can include transporter-delivery aids, including nanoparticles, nanomicelles, liposomes, microemulsions and/or enzymes (e.g., to allow delivery of one or more active ingredients notwithstanding various static and dynamic barriers). Static ocular barriers to delivery can include different layers of cornea, sclera, and retina including blood aqueous and blood-retinal barriers. Dynamic ocular barriers to delivery can include choroidal and conjunctival blood flow, lymphatic clearance, and tear dilution. An additive with transporterdelivery aid functionality can also aid ocular delivery despite efflux pumps.

[0067] It will also be appreciated that additive(s) and the blood-derived serum can be combined in various ways to form a suspension, colloid, solution (e.g., liquid solution), gel, bioadhesive gel, fibrin sealant, or other form-factor for topical ophthalmic delivery (e.g., ocular application on or around the eye). Examples of topical ophthalmic delivery can include eye drops placed onto the eye surface, ointment applied on or around the eye, etc.

[0068] Alternatively, the foregoing embodiments can be modified for intraocular delivery in the eyeball itself or surrounding tissue (e.g., via hypodermic needle injection). In another alternative example, the foregoing embodiments can be modified for implementation with a patch, adhesive (e.g., bioadhesive gel), tape, gauze, electrospun fibers, or a biocompatible polymer. For instance, a combination of a blood-derived serum and an additive can be applied on (or embedded within) a patch that can be adhered over an animal’s eye or eye lid. In certain implementations of this embodiment, the combination of a blood-derived serum and an additive (e.g., the active ingredients) are implemented with a transmucosal patch such that the active ingredients enter the animal’s blood stream through or across a mucous membrane, such as a tear duct or tear film.

[0069] The foregoing description, for purposes of explanation, used specific nomenclature to provide a thorough understanding of the described examples. However, it will be apparent to a person of ordinary skill in the art that the specific details are not required in order to practice the described examples. Thus, the foregoing descriptions of the specific examples described herein are presented for purposes of illustration and description. They are not intended to be exhaustive or to limit the examples to the precise forms disclosed.

[0070] It will be apparent to one of ordinary skill in the art that many modifications and variations are possible in view of the above teachings. Indeed, various inventions have been described herein with reference to certain specific aspects and examples. However, they will be recognized by those skilled in the art that many variations are possible without departing from the scope and spirit of the inventions disclosed herein. Specifically, those inventions set forth in the claims below are intended to cover all variations and modifications of the inventions disclosed without departing from the spirit of the inventions. The terms “including” or “includes” as used in the specification shall have the same meaning as the term “comprising.”

The term “about” should be interpreted as +/- 10%, unless otherwise specified.

Claims

CLAIMS What is claimed is:

1. A composition for topical ophthalmic delivery in companion animals, the composition comprising: a blood-derived serum; and an antibiotic.

2. The composition of claim 1, wherein the antibiotic comprises an active ingredient from the fluoroquinolone family.

3. The composition of claim 1, wherein the antibiotic comprises an active ingredient that includes ciprofloxacin or levofloxacin.

4. The composition of claim 1, wherein the composition comprises a ratio of the blood-derived serum relative to the antibiotic that is between about 2 to 1 (2:1) to about 10 to 1 (10:1).

5. The composition of claim 1, wherein the blood-derived serum comprises bovine serum.

6. A composition for topical ophthalmic delivery in companion animals, the composition comprising: a blood-derived serum; and an eye lubricant.

7. The composition of claim 6, wherein the eye lubricant comprises sodium hyaluronate.

8. The composition of claim 6, wherein the eye lubricant comprises hyaluronic acid.

9. The composition of claim 6, wherein the composition comprises a ratio of the blood-derived serum relative to the eye lubricant that is between about 2 to 1 (2: 1) to about 10 to 1 (10: 1).

10. The composition of claim 6, wherein the blood-derived serum comprises bovine serum.

11. A composition for topical ophthalmic delivery in companion animals, the composition comprising: a blood-derived serum; and an antihistamine.

12. The composition of claim 11, wherein the antihistamine comprises pheniramine maleate.

13. The composition of claim 11, wherein the composition comprises a ratio of the blood-derived serum relative to the antihistamine that is between about 2 to 1 (2: 1) to about 10 to 1 (10: 1).

14. The composition of claim 11, wherein the blood-derived serum comprises bovine serum.

15. A composition for topical ophthalmic delivery in companion animals, the composition comprising: a blood-derived serum; and a vitamin.

16. The composition of claim 15, wherein the vitamin includes vitamin Bl.

17. The composition of claim 15, wherein the composition comprises a ratio of the blood-derived serum relative to the vitamin that is about 2 to 1 (2: 1) to about 10 to 1 (10: 1).

18. The composition of claim 15, wherein the blood-derived serum comprises bovine serum.

19. A composition for topical ophthalmic delivery in companion animals, the composition comprising: a blood-derived serum; and a lysed white blood cell product.

20. The composition of claim 19, wherein the lysed white cell product includes a protein.

21. The composition of claim 19, wherein the blood-derived serum comprises bovine serum.

22. A composition for topical ophthalmic delivery in companion animals, the composition comprising: a blood-derived serum; and an additive.

23. The composition of claim 22, wherein the additive includes at least one of an antibiotic, an antihistamine, a vitamin, or a lysed white blood cell product.

24. A method of manufacturing any and all compositions described, referred to, exemplified, or shown in the present disclosure.

25. The method of claim 24, including one or more steps for mixing, product separation, storage, or packaging.

26. An apparatus for manufacturing any and all compositions described, referred to, exemplified, or shown in the present disclosure.

27. The apparatus of claim 26, wherein the apparatus performs one or more steps of mixing, product separation, storage, or packaging.