Compositions comprising lactoperoxidase and iodide salt and their use for the treatment of equine gastric ulcer syndrome

Abstract

A composition containing lactoperoxidase and one or more iodized salts is used to treat equine gastric ulcer syndrome.

Description

Technical Field

[0001] This invention relates to pharmaceutical compositions for the treatment or prevention of equine gastric ulcer syndrome. In particular, this invention relates to pharmaceutical compositions for the treatment of equine scaly gastric ulcers and / or equine glandular gastric ulcers. The invention also provides a feed additive or feed supplement composition that can be used for the treatment, including the preventative treatment of equine gastric ulcer syndromes such as equine scaly gastric ulcers and / or equine glandular gastric ulcers.

[0002] The present invention also relates to pharmaceutical compositions for treating gastrointestinal bacterial infections in mammals. These compositions are particularly effective in treating bacterial infections in mammals such as lambs, calves, humans, pigs, and horses. Suitably, the mammal may be a monogastric mammal. The present invention also provides a feed additive or feed supplement composition that can be used to treat (including preventative treatment) gastrointestinal bacterial infections in animals.

[0003] The present invention also provides animal feed comprising the feed additive or feed supplement compositions disclosed herein. The disclosed compositions can be used to improve gastrointestinal bacterial infections without the need for antibiotics.

[0004] Furthermore, the compositions of the present invention can be used to treat gastric ulcers, particularly gastric ulcers in horses, cats, and dogs. Background Technology

[0005] Equine gastric ulcer syndrome (EGUS) describes the development of ulcers in the lining of the stomach in horses. The severity of the ulcers varies, ranging from mild inflammation of the stomach wall to severe ulcers and bleeding; gastric perforation can lead to colic and sudden death.

[0006] The horse's stomach consists of two distinct regions, the squamous and glandular mucosa, separated by folded edges. The glandular mucosa, located ventrally, comprises gastric glands that secrete hydrochloric acid, pepsinogen, histamine, mucus, and sodium bicarbonate. The dorsal side of the stomach is covered by squamous epithelium. The glandular mucosa is located approximately in the lower two-thirds of the stomach, while the squamous mucosa is located in the upper third. Gastric ulcers are classified according to the location of the ulcer / lesion: Equine glandular gastric ulcer (EGGD) refers to disease of the glandular portion of the stomach, and equine squamous gastric ulcer (ESGD) refers to disease of the squamous mucosa portion. Equine gastric ulcer syndrome (EGUS) is a general term encompassing diseases of any part of the stomach.

[0007] Gastric ulcers are ulcers that form on the lining of the stomach. These are very common in horses, with an estimated 50-90% suffering from them. EGUS (excessive gastric ulcers) is likely a major cause of poor performance in racehorses due to the high prevalence of ulcers. The causes of ulcers are varied: racehorses are typically fed a grain-rich diet and have long fasting periods between meals during exercise; exercise has been shown to increase stomach acid production and reduce blood flow to the gastrointestinal tract, which, combined with reduced saliva production and confinement, is believed to contribute to gastric ulcers. Increased severity of gastric ulcers is associated with an increased risk of colic.

[0008] As mentioned above, EGUS is very common in high-performance horses and increases significantly in horses undergoing training. EGUS is thought to be caused by an imbalance between mucosal aggressive factors such as hydrochloric acid, pepsin, bile acids, and organic acids and mucosal protective factors such as mucus and bicarbonate.

[0009] Current treatment strategies follow the "no acid, no ulcer" motto, focusing on neutralizing existing stomach acid or blocking the secretion of new stomach acid to increase gastric pH. Stomach acid production can be inhibited by using proton pump inhibitors such as rabeprazole, lansoprazole, dexlansoprazole, tretinoin, omeprazole, and esomeprazole.

[0010] EGUS can be treated by protecting the damaged gastric mucosa with mucosal protectants such as sucralfate (oral) and misoprostol (injection), neutralizing gastric acid with antacids such as magnesium hydroxide, or by inhibiting acid production with oral proton pump inhibitors (PPIs) or histamine type 2 (H2) receptor antagonists such as ranitidine.

[0011] This treatment method has several drawbacks. Mucosal protectants must be continuously present and applied to all sites of the ulcer to promote healing. This requires high doses of mucosal protectants and frequent administration, with sucralfate and misoprostol administered at least twice daily. Similarly, antacids must be continuously present in the stomach, and in sufficient quantities to neutralize the large amounts of continuously produced gastric HCl. The most effective approach is to inhibit acid production. Currently, there is an approved drug for treating equine gastric ulcers, namely omeprazole, which reduces gastric acid secretion.

[0012] US200220202797A1 describes a method for treating and / or preventing gastric ulcers, the method comprising administering by injection a therapeutically effective amount of a composition comprising: a) a first agent selected from medium-chain triglycerides and long-chain triglycerides; and b) a second agent comprising a proton pump inhibitor or a pharmaceutically or veterinarily acceptable salt, wherein the composition is adapted to sustainably release a therapeutically effective amount of the proton pump inhibitor to a subject in need. The proton pump inhibitor is omeprazole.

[0013] EP2925335B1 relates to a composition for preventing rebound ulcers in horses after administration of omeprazole, or for treating equine gastric ulcer syndrome in horses in need, comprising administering to the horse a therapeutically effective amount of the composition, wherein the composition comprises: (i) a preparation obtained from sea buckthorn, wherein the preparation obtained from sea buckthorn is a concentrate, metabolite, component or extract of sea buckthorn fruit, or a combination thereof, (ii) glutamine and (iii) aloe vera extract, pectin and lecithin.

[0014] Helicobacter pylori species are associated with gastric and duodenal ulcers in humans, but reports indicate that Helicobacter pylori is not associated with EGUS in horses.

[0015] The field of nutritional supplements continues to evolve, and the use of oils rich in omega-3 is becoming increasingly popular. A recent study evaluating supplements from thoroughbred horses showed that long-chain polyunsaturated fatty acids from fish are superior in preventing ESGD and altering inflammatory profiles compared to combined polyunsaturated fatty acids from a corn and flaxseed blend.

[0016] The use of omeprazole in humans has been associated with complications, including increased risk of rebound hyperacidity, antibiotic-associated and nonspecific diarrhea, and increased risk of fractures. There are also concerns that omeprazole may increase the risk of fractures in horses. Therefore, long-term use of omeprazole for the prevention of EGUS is not recommended. Having an effective, low-cost alternative treatment and prevention protocol would be advantageous, such as administering EGUS orally to horses for the management, treatment, and / or prevention of EGUS. This invention provides such a solution.

[0017] Lactoperoxidase (LPO) is a peroxidase secreted by the mammary glands, salivary glands, and other mucosal glands. LPO catalyzes the oxidation of several inorganic and organic substrates via hydrogen peroxide. For example, lactoperoxidase catalyzes the oxidation of thiocyanate to hypothiocyanate, bromide to hypobromide, and iodide to hypoiodide by hydrogen peroxide. These oxidases typically have short lifespans but possess potent bactericidal activity.

[0018] The lactoperoxidase system involves the use of lactoperoxidase, thiocyanate, and hydrogen peroxide as chemical preservatives in raw milk where refrigeration is not possible. Lactoperoxidase catalyzes the oxidation of thiocyanate ions to hypothiocyanate in the presence of hydrogen peroxide. The acidity and hypothiocyanate ions in milk are considered to be the cause of the antibacterial effect of the lactoperoxidase system.

[0019] The exact mechanism supporting the antibacterial properties of the LPO system remains unclear. Many experimental protocols have been described, some reporting bacterial inhibition, but bacteria typically regenerate after a period of time, thus the observed effect is bacteriostatic rather than bactericidal.

[0020] International Patent Application Publication No. WO2012 / 140272 relates to a composition for killing microorganisms, comprising reactive oxygen species or components capable of producing reactive species, said composition being capable of delivering reactive oxygen species to a level of at least 0.4 mmol / L within 24 hours. Example compositions include potassium iodide, lactoperoxidase, and glucose oxidase. Glucose oxidase is an oxidoreductase that catalyzes the oxidation of glucose to produce hydrogen peroxide and D-gluconic acid-δ-lactone. The composition can be used to treat bacterial infections or to control bacterial contamination, thereby avoiding the use of antibiotics. Such infections include mastitis, tuberculosis, cystic fibrosis, and other lung infections, as well as contamination that may be caused by biofilm formation on surfaces such as medical devices. However, the composition is also suitable for treating viral, yeast, or fungal infections, or controlling contamination by such organisms.

[0021] U.S. Patent No. 5066497 discloses an antibacterial solution comprising 0.01% to 2% iodine derived from a povidone-iodine complex and approximately 0.5% to 5% hydrogen peroxide as a nascent oxygen source. The solution is described as having practical applications in the treatment of mastitis.

[0022] Currently, commercial applications based on lactoperoxidase systems include mouthwash, toothpaste, food preservatives, and disinfectants. These applications are primarily based on inhibiting microbial growth, rather than killing cells and completely eliminating bacterial communities in various environments.

[0023] US Patent No. 5,607,681 discloses a composition comprising iodide anion, thiocyanate anion, D-glucose, glucose oxidase, and lactoperoxidase. These compositions are described as having preservative effects, capable of preventing microbial spoilage of various products, such as cosmetics, toiletries, and pharmaceutical preparations; household and industrial preparations, such as detergents; and foods, such as milk and dairy products, and animal feed. The patent describes antimicrobial activity for up to 72 hours but does not describe any therapeutic applications of the system.

[0024] Wet mouth disease (WMD) is a term used to describe a range of clinical symptoms in newborn lambs. These symptoms include excessive salivation, bloating, meconium retention, lethargy, and inability to suckle. It is caused by infection and colonization of the small intestine by *E. coli*, which grows rapidly and releases toxins. The disease is believed to be caused by poor hygiene, such as ingestion of *E. coli* from the ewe's wool while the lamb is searching for its udder, or through soiled bedding, leading to bacterial infection and delayed or insufficient intake of colostrum in the first few hours of life. This is particularly problematic in densely populated indoor environments, where wet mouth disease can lead to severe losses, with morbidity sometimes reaching 24% and mortality rates as high as 83% (Eales FA, Small J, Gilmour JS, Donachie W, FitzSimons J, Dingwall WS. A fieldstudy of watery mouth: clinical, epidemiological, biochemical, haematological and bacteriological observations. Vet Rec. 1986 Nov 29;119(22):543-7). Wet mouth disease is usually treated by administering antibiotics to affected lambs. For example, lambs can be treated with neomycin, streptomycin, and / or amoxicillin. In addition, lambs are often given antibiotics prophylactically to prevent bacterial infections, such as E. coli infection.

[0025] Escherichia coli infection, or colibacillosis, is a major disease in pigs, typically causing illness and death in newborn and recently weaned pigs. It is becoming a leading disease of clinical and economic importance in the swine industry. The most common treatment for E. coli infection is the use of antibiotics, both as a preventative measure and as an early intervention. Due to concerns about rising antibiotic resistance and its transfer through the food chain, alternative solutions are needed. Furthermore, a common method for controlling E. coli infection in newly weaned piglets in the swine industry is the addition of zinc oxide to their diets; zinc oxide can be included at a rate of 3 wt% of the feed intake. Once the labeled products are exhausted by July 2022, the EU will ban the use of large amounts of zinc oxide (e.g., more than 1 wt% based on feed intake) as a feed additive in pig diets, thus necessitating an alternative approach to address bacterial infections in piglets.

[0026] WO02 / 054872 describes a liquid antimicrobial composition comprising (i) a mixture of iodide anions and thiocyanate anions, (ii) periodic acid or an alkali metal salt thereof, and optionally a peroxidase. The composition can be used as a microbial agent.

[0027] WO2008045696A2 describes a therapeutic composition for treating vaginal diseases, which utilizes a peroxidase-producing enzyme and a peroxidase. The composition may specifically include lactoperoxidase and glucose oxidase.

[0028] This document describes compositions, treatment methods, feed additives, and feed supplements. The compositions can be used to treat, prevent, improve, or reduce the effects of EGUS, including EGGD and / or EGSD. Furthermore, the compositions of this invention can be used to treat, prevent, and / or improve wet snout disease in lambs, as well as E. coli infection and diarrhea and scour in pigs and / or calves, particularly dairy calves. The compositions can be used to reduce the effects of bacterial infections on mammals, particularly on animals such as lambs, cattle, especially calves, such as dairy calves, pigs, horses, and humans. Summary of the Invention

[0029] In one aspect, the present invention provides a composition, such as a pharmaceutical composition, comprising: lactoperoxidase, iodized salt, and a pharmaceutically acceptable carrier and / or excipient, for the treatment or prevention of equine gastric ulcer syndrome (EGUS), optionally wherein equine gastric ulcer syndrome includes equine squamous gastric ulcer (ESGD) and / or equine glandular gastric ulcer (EGGD).

[0030] The composition is used to treat EGUS, such as ESGD and / or EGGD, in equines (e.g., horses and / or ponies). These horses may be high-performance horses, such as racehorses, show jumping horses, hunting horses, eventing horses, or recreational horses or ponies.

[0031] The composition may not contain peroxides or peroxide sources. Suitablely, the treatment does not include the application of peroxides or peroxide sources.

[0032] The composition may be free of thiocyanate or a thiocyanate source. Suitablely, the treatment does not include the application of thiocyanate or a thiocyanate source.

[0033] Appropriately, the weight ratio of lactoperoxidase to iodized salt is 1:10 to 10:1, preferably 1:3 to 3:1, most preferably 1:1.3 to 1.3:1, for example about 1:1.

[0034] Iodized salt can be selected from sodium iodide, potassium iodide, lithium iodide, ammonium iodide, calcium iodide, cesium iodide, hydrogen iodide, rhodium iodide, and combinations thereof, with sodium iodide and / or potassium iodide being preferred, and potassium iodide being more preferred.

[0035] The composition is suitable for oral dosage forms, such as solid dosage forms, like tablets or powders, or liquid dosage forms, including suspensions. The composition is formulated for oral administration.

[0036] The composition may also contain vitamin C.

[0037] The composition may contain two or more excipients.

[0038] The composition may contain one or more of the following: magnesium stearate, lactose, glucose, microcrystalline cellulose, starch (corn), silicon dioxide, titanium dioxide, zinc oxide, colostrum, hydroxypropyl methylcellulose, stearic acid, sodium starch glycolate, gelatin, talc, sucrose, calcium stearate, and povidone. For example, the composition may contain magnesium stearate, microcrystalline cellulose, zinc oxide, and colostrum.

[0039] Appropriately, treatment or prevention of equine gastric ulcer syndrome, such as equine squamous gastric ulcer and / or equine glandular gastric ulcer, includes daily administration of at least 0.24 mmol of iodized salt and at least 40 mg of lactoperoxidase. Preferably, treatment includes daily administration of at least 0.36 mmol of iodized salt and at least 60 mg of lactoperoxidase. More preferably, treatment includes daily administration of at least 0.48 mmol of iodized salt and at least 80 mg of lactoperoxidase.

[0040] For example, the treatment may include administering 40 mg of iodized salt and at least 40 mg of lactoperoxidase daily, preferably, the treatment includes administering at least 60 mg of iodized salt and at least 60 mg of lactoperoxidase daily, and more preferably, the treatment includes administering at least 80 mg of iodized salt and at least 80 mg of lactoperoxidase daily.

[0041] Appropriately, treatment may include daily administration of 0.24 mmol to 1.2 mmol of iodized salt, for example, 0.36 mmol to 1.2 mmol of iodized salt, or 0.48 mmol to 1.2 mmol of iodized salt. Appropriately, treatment may include daily administration of 0.24 mmol to 0.6 mmol of iodized salt, for example, 0.36 mmol to 0.6 mmol of iodized salt, or 0.48 mmol to 0.6 mmol of iodized salt. For example, treatment may include daily administration of 0.24 mmol to 0.51 mmol of iodized salt, for example, 0.36 mmol to 0.51 mmol of iodized salt, or 0.48 mmol to 0.51 mmol of iodized salt.

[0042] For example, treatment may include administering 40 to 200 mg of iodized salt daily, such as 60 to 200 mg of iodized salt daily, or 80 to 200 mg of iodized salt daily. Treatment may also include administering 40 to 100 mg of iodized salt daily, such as 60 to 100 mg of iodized salt daily, or 80 to 100 mg of iodized salt daily. Treatment may also include administering 40 to 85 mg of iodized salt daily. For example, when treatment includes administering a composition containing potassium iodide, treatment may include administering 40 to 200 mg of potassium iodide daily, preferably 40 to 100 mg of potassium iodide salt daily, such as 60 to 100 mg of potassium iodide salt daily, and optionally 80 to 100 mg of potassium iodide salt daily. Most preferably, treatment includes administering 40 to 85 mg of the potassium salt daily.

[0043] Treatment may include administering 40 to 200 mg of lactoperoxidase daily, for example, 60 to 200 mg of lactoperoxidase daily, or 80 to 200 mg of lactoperoxidase daily. Optionally, treatment may include administering 40 to 100 mg of lactoperoxidase daily, for example, 60 to 100 mg of lactoperoxidase daily, or 80 to 100 mg of lactoperoxidase daily. Most preferably, treatment may include administering 40 to 85 mg of lactoperoxidase daily.

[0044] The treatment may include daily administration of 0.24 mmol to 1.2 mmol of iodized salt and 40 to 200 mg of lactoperoxidase, for example, daily administration of 0.24 mmol to 0.6 mmol of iodized salt and 40 to 100 mg of lactoperoxidase, for example, daily administration of 0.36 mmol to 0.6 mmol of iodized salt and 60 to 100 mg of lactoperoxidase, optionally daily administration of 0.48 mmol to 0.6 mmol of iodized salt and 80 to 100 mg of lactoperoxidase. Further optionally, the treatment may include daily administration of 0.24 mmol to 0.51 mmol of iodized salt and 40 to 85 mg of lactoperoxidase.

[0045] Suitablely, the treatment may include daily administration of 40 to 200 mg of iodized salt and 40 to 200 mg of lactoperoxidase, for example, daily administration of 60 to 200 mg of iodized salt and 60 to 200 mg of lactoperoxidase, optionally, daily administration of 80 to 200 mg of iodized salt and 80 to 200 mg of lactoperoxidase. Suitablely, the treatment may include daily administration of 40 to 100 mg of iodized salt and 40 to 100 mg of lactoperoxidase, for example, daily administration of 60 to 100 mg of iodized salt and 60 to 100 mg of lactoperoxidase, for example, daily administration of 80 to 100 mg of iodized salt and 80 to 100 mg of lactoperoxidase. More suitablely, the treatment may include daily administration of 40 to 85 mg of iodized salt and 40 to 85 mg of lactoperoxidase.

[0046] Suitablely, the treatment lasts for at least four weeks, preferably at least eight weeks, and more preferably at least 12 weeks. Most preferably, the treatment includes daily application of the composition, for example, daily application during training of equines (such as horses). The treatment may include daily application of the composition for at least four days a week, preferably at least five days a week.

[0047] Compositions for the treatment and / or prevention of EGUS, such as pharmaceutical compositions, such as EGSD and / or EGGD as described herein, may be formulated as one or more unit doses.

[0048] The unit dose of the composition may contain lactoperoxidase in a content of 0.5 mg to 200 mg, for example 1 mg to 100 mg, preferably 5 mg to 50 mg, more preferably 8 mg to 20 mg, for example 8 mg to 12 mg.

[0049] The unit dose of the composition may contain iodized salt in a content of 0.003 mmol to 1.2 mmol, for example 0.006 mmol to 0.6 mmol, preferably 0.030 mmol to 0.30 mmol, more preferably 0.048 mmol to 0.072 mmol.

[0050] For example, a unit dose of the composition may contain iodized salt in a content of 0.5 mg to 200 mg, such as 1 mg to 100 mg, preferably 5 mg to 50 mg, more preferably 8 mg to 20 mg, such as 8 mg to 12 mg.

[0051] The unit dose of the composition may contain about 0.5 wt% to about 15 wt%, preferably about 0.5 wt% to about 5 wt%, more preferably about 1 wt% to about 2 wt%, for example about 1 wt% to 1.5 wt% of lactoperoxidase.

[0052] The unit dose of the composition may contain iodized salt in a content of about 0.5 wt% to about 15 wt%, preferably about 0.5 wt% to about 5 wt%, more preferably about 1 wt% to about 2 wt%, for example about 1 wt% to 1.5 wt%.

[0053] Locally, each unit dose of the composition comprises lactoperoxidase in an amount of about 8 mg to about 20 mg, and in an amount of about 0.5 wt% to about 5 wt% based on the total weight of the unit dose, and wherein the iodized salt is potassium iodide, said potassium iodide in an amount of about 8 mg to about 20 mg, and in an amount of about 0.5 wt% to about 5 wt% based on the total weight of the unit dose, and wherein said composition optionally contains vitamin C, and optionally contains zinc oxide. Optionally, at least 5 unit doses are administered daily, optionally at least 6 unit doses are administered daily, optionally at least 8 unit doses are administered daily, preferably at least 10 unit doses are administered daily.

[0054] Adjust the number of dosing units to achieve the desired dose. For example, if a unit contains 8 mg of lactoperoxidase and 8 mg of potassium iodide, administer 10 units to achieve a daily dose of 80 mg of lactoperoxidase and 80 mg of potassium iodide.

[0055] Suitably, the composition contains about 8 mg to about 20 mg per unit dose of lactoperoxidase at a content of about 0.5 wt% to about 5 wt% based on the total weight of the unit dose, and wherein the iodized salt is potassium iodide at a content of about 8 mg to about 20 mg at a content of about 0.5 wt% to about 5 wt% based on the total weight of the unit dose, and wherein the composition optionally contains vitamin C and optionally contains zinc oxide, and is administered at least 6 unit doses daily, optionally at least 8 unit doses daily, preferably at least 10 unit doses daily.

[0056] For example, the unit dose of the composition may contain about 8 mg to about 12 mg of lactoperoxidase in a content of about 0.5 wt% to about 5 wt% based on the total weight of the unit dose, the iodized salt being potassium iodide in a content of about 8 mg to about 12 mg in a content of about 0.5 wt% to about 5 wt% based on the total weight of the unit dose, and wherein the composition optionally contains vitamin C and optionally contains zinc oxide, and is administered at least 6 unit doses daily, optionally at least 8 unit doses daily, preferably at least 10 unit doses daily.

[0057] The compositions described herein, such as pharmaceutical compositions, may be formulated as feed additives or feed supplements as described herein.

[0058] In another aspect, the present invention provides a combination for treating equine gastric ulcer syndromes such as equine squamous gastric ulcer and / or equine glandular gastric ulcer, the combination comprising: lactoperoxidase and iodized salt; wherein the lactoperoxidase and iodized salt are applied sequentially or simultaneously to the horse or foal.

[0059] Appropriately, the relative weight ratio of lactoperoxidase to iodized salt is 1:10 to 10:1, preferably about 1:2 to 2:1, and more preferably about 1:1.3 to 1.3:1.

[0060] The combination is used to treat EGUS, such as ESGD and / or EGGD in equines (e.g., horses and / or ponies). These horses may be high-performance horses, such as racehorses, show jumping horses, hunting horses, eventing horses, or recreational horses or ponies.

[0061] Suitablely, the combination does not contain peroxides or peroxide sources. Suitablely, the treatment does not include the application of peroxides or peroxide sources.

[0062] Suitablely, the combination does not contain thiocyanate or a thiocyanate source. Suitablely, the treatment does not include the administration of thiocyanate or a thiocyanate source.

[0063] Iodized salt can be selected from sodium iodide, potassium iodide, lithium iodide, ammonium iodide, calcium iodide, cesium iodide, hydrogen iodide, rhodium iodide, and combinations thereof, with sodium iodide and / or potassium iodide being preferred, and potassium iodide being more preferred.

[0064] The combination may involve administering one or more oral dosage forms. Oral dosage forms may be solid dosage forms, such as tablets or powders, or liquid dosage forms, including suspensions.

[0065] The combination may also contain vitamin C.

[0066] The combination may contain one or more excipients. For example, one or more oral dosage forms may contain one or more excipients.

[0067] For example, a combination of one or more oral dosage forms may contain one or more of the following: magnesium stearate, lactose, glucose, microcrystalline cellulose, starch (corn), silicon dioxide, titanium dioxide, zinc oxide, colostrum, hydroxypropyl methylcellulose, stearic acid, sodium starch glycolate, gelatin, talc, sucrose, calcium stearate, and povidone. For instance, the composition may contain magnesium stearate, microcrystalline cellulose, zinc oxide, and colostrum.

[0068] For example, a combination of one or more oral dosage forms may contain one or more flavoring agents, sweeteners, and / or colorings.

[0069] As described above, treatment for equine gastric ulcer syndrome, such as equine squamous gastric ulcer and / or equine glandular gastric ulcer, appropriately comprises daily administration of at least 0.24 mmol of iodized salt and at least 40 mg of lactoperoxidase. Preferably, the treatment comprises daily administration of at least 0.36 mmol of iodized salt and at least 60 mg of lactoperoxidase. More preferably, the treatment comprises daily administration of at least 0.48 mmol of iodized salt and at least 80 mg of lactoperoxidase. For example, the treatment may comprise daily administration of 40 mg of iodized salt and at least 40 mg of lactoperoxidase. Preferably, the treatment comprises daily administration of at least 60 mg of iodized salt and at least 60 mg of lactoperoxidase. More preferably, the treatment comprises daily administration of at least 80 mg of iodized salt and at least 80 mg of lactoperoxidase.

[0070] Appropriately, treatment may include daily administration of 0.24 mmol to 1.2 mmol of iodized salt, for example, 0.36 mmol to 1.2 mmol of iodized salt, or 0.48 mmol to 1.2 mmol of iodized salt. Appropriately, treatment may include daily administration of 0.24 mmol to 0.6 mmol of iodized salt, for example, 0.36 mmol to 0.6 mmol of iodized salt, or 0.48 mmol to 0.6 mmol of iodized salt. For example, treatment may include daily administration of 0.24 mmol to 0.51 mmol of iodized salt, for example, 0.36 mmol to 0.51 mmol of iodized salt, or 0.48 mmol to 0.51 mmol of iodized salt.

[0071] For example, treatment may include administering 40 to 200 mg of iodized salt daily, such as 60 to 200 mg of iodized salt daily, or 80 to 200 mg of iodized salt daily. Treatment may also include administering 40 to 100 mg of iodized salt daily, such as 60 to 100 mg of iodized salt daily, or 80 to 100 mg of iodized salt daily. Treatment may also include administering 40 to 85 mg of iodized salt daily. For example, when treatment includes administering a composition containing potassium iodide, treatment may include administering 40 to 200 mg of potassium iodide daily, preferably 40 to 100 mg of potassium iodide salt daily, such as 60 to 100 mg of potassium iodide salt daily, and optionally 80 to 100 mg of potassium iodide salt daily. Most preferably, treatment includes administering 40 to 85 mg of potassium salt daily.

[0072] Treatment may include administering 40 to 200 mg of lactoperoxidase daily, for example, 60 to 200 mg of lactoperoxidase daily, or 80 to 200 mg of lactoperoxidase daily. Optionally, treatment may include administering 40 to 100 mg of lactoperoxidase daily, for example, 60 to 100 mg of lactoperoxidase daily, or 80 to 100 mg of lactoperoxidase daily. Most preferably, treatment may include administering 40 to 85 mg of lactoperoxidase daily.

[0073] Treatment may include daily administration of 0.24 mmol to 1.2 mmol of iodized salt and 40 to 200 mg of lactoperoxidase, for example, daily administration of 0.24 mmol to 0.6 mmol of iodized salt and 40 to 100 mg of lactoperoxidase, for example, daily administration of 0.36 mmol to 0.6 mmol of iodized salt and 60 to 100 mg of lactoperoxidase, optionally daily administration of 0.48 mmol to 0.6 mmol of iodized salt and 80 to 100 mg of lactoperoxidase. Further optionally, treatment may include daily administration of 0.24 mmol to 0.51 mmol of iodized salt and 40 to 85 mg of lactoperoxidase.

[0074] Suitablely, the treatment may include daily administration of 40 to 200 mg of iodized salt and 40 to 200 mg of lactoperoxidase, for example, daily administration of 60 to 200 mg of iodized salt and 60 to 200 mg of lactoperoxidase, optionally, daily administration of 80 to 200 mg of iodized salt and 80 to 200 mg of lactoperoxidase. Suitablely, the treatment may include daily administration of 40 to 100 mg of iodized salt and 40 to 100 mg of lactoperoxidase, for example, daily administration of 60 to 100 mg of iodized salt and 60 to 100 mg of lactoperoxidase, for example, daily administration of 80 to 100 mg of iodized salt and 80 to 100 mg of lactoperoxidase. More suitably, the treatment may include preferably daily administration of 40 to 85 mg of iodized salt and 40 to 85 mg of lactoperoxidase.

[0075] Appropriately, the treatment lasts for at least 4 weeks, preferably at least 8 weeks, and more preferably at least 12 weeks. Most preferably, the treatment is administered daily, for example, daily during the training of equines (such as horses).

[0076] The combination may contain at least 0.24 mmol of iodized salt and at least 40 mg of lactoperoxidase. Preferably, the combination may contain at least 0.36 mmol of iodized salt and at least 60 mg of lactoperoxidase; more preferably, the combination may contain at least 0.48 mmol of iodized salt and at least 80 mg of lactoperoxidase.

[0077] Suitablely, the combination comprises 0.24 mmol to 1.2 mmol of iodized salt, preferably 0.24 to 0.60 mmol of iodized salt, more preferably 0.24 mmol to 0.51 mmol of iodized salt.

[0078] For example, the combination may contain 40 to 200 mg of iodized salt, preferably 40 to 100 mg of iodized salt, more preferably 40 to 85 mg of iodized salt. Suitably, the combination may contain 40 to 200 mg of potassium iodide, preferably 40 to 100 mg of potassium iodide, more preferably 40 to 85 mg of potassium iodide.

[0079] Suitable, the combination contains 40 to 200 mg of lactoperoxidase, preferably 40 to 100 mg of lactoperoxidase, more preferably 40 to 85 mg of lactoperoxidase.

[0080] For example, the combination may contain at least 40 mg of iodized salt and at least 40 mg of lactoperoxidase. Preferably, the combination may contain at least 60 mg of iodized salt and at least 60 mg of lactoperoxidase. More preferably, the combination contains at least 80 mg of iodide and at least 80 mg of lactoperoxidase.

[0081] Preferably, the combination is applied daily. As described herein, the combination can be formulated as a feed additive.

[0082] The present invention also discloses a method for treating and / or preventing EGUS, optionally wherein the EGUS is EGSD or EGGD, the method comprising administering to an animal in need the compositions or combinations disclosed herein, preferably daily or for a period of time disclosed herein.

[0083] The present invention also discloses a feed additive composition or dietary / feed supplement composition comprising: lactoperoxidase and iodized salt, wherein the composition does not contain peroxide or peroxide source; and wherein the composition does not contain thiocyanate or thiocyanate source; wherein the content of lactoperoxidase is at least 40 mg, and wherein the content of iodized salt is at least 0.24 mmol.

[0084] Optionally, the weight ratio of lactoperoxidase to iodized salt is in the range of 1:2 to 2:1, for example, 1:1.3 to 1.3:1.

[0085] Iodized salt can be selected from sodium iodide, potassium iodide, lithium iodide, ammonium iodide, calcium iodide, cesium iodide, hydrogen iodide, rhodium iodide, and combinations thereof, with sodium iodide and / or potassium iodide being preferred, and potassium iodide being more preferred.

[0086] The composition may be in tablet, powder, or oral suspension form.

[0087] The feed additive composition or feed supplement composition may contain at least 0.24 mmol of iodized salt and at least 40 mg of lactoperoxidase, preferably at least 0.36 mmol of iodized salt and at least 60 mg of lactoperoxidase, more preferably at least 0.48 mmol of iodized salt and at least 80 mg of lactoperoxidase.

[0088] The feed additive composition or feed supplement composition may contain 0.24 mmol to 1.2 mmol of iodized salt, preferably 0.24 mmol to 0.6 mmol of iodized salt. Optionally, the feed additive contains 0.36 mmol to 1.2 mmol of iodide salt, for example 0.36 mmol to 0.6 mmol of iodized salt, most preferably 0.24 mmol to 0.51 mmol of iodide salt.

[0089] For example, a feed additive composition or feed supplement composition may contain 40 to 200 mg of iodized salt, preferably 40 to 120 mg of iodized salt, such as 40 to 100 mg of iodized salt, and most preferably 40 to 85 mg of iodized salt. For example, when the iodized salt contains potassium iodide, the feed additive composition or feed supplement composition may contain 40 to 200 mg of potassium iodide, preferably 40 to 120 mg of potassium iodide, such as 40 to 100 mg of potassium iodide, and most preferably 40 to 85 mg.

[0090] The feed additive composition or feed supplement composition may contain 40 to 200 mg of lactoperoxidase, preferably 40 to 120 mg of lactoperoxidase, for example 40 to 100 mg of lactoperoxidase, and most preferably 40 to 85 mg of lactoperoxidase.

[0091] Feed additive compositions or feed supplement compositions can be formulated into unit dosage forms. Feed additive compositions or feed supplement compositions can be administered as one or more unit doses. Preferably, the feed additive compositions or feed supplement compositions are administered daily to equines (e.g., horses or ponies).

[0092] Suitable, a unit dose of feed additive composition or feed supplement composition may contain 5 to 20 mg of lactoperoxidase, preferably 8 to 15 mg of lactoperoxidase, more preferably 8 to 12 mg of lactoperoxidase.

[0093] The feed additive composition or feed supplement composition may contain, for example, lactoperoxidase in amounts of about 0.5 wt% to about 15 wt% based on the total weight of the unit dose, preferably about 0.5 wt% to about 5 wt%, more preferably about 1 wt% to about 2 wt%, such as about 1 wt% to about 1.5 wt% of the total weight of the unit dose.

[0094] Suitable, a unit dose of feed additive composition or feed supplement composition may contain 5 to 20 mg of lactoperoxidase, preferably 8 to 15 mg of lactoperoxidase, more preferably 8 to 12 mg of lactoperoxidase, and wherein the lactoperoxidase content is from about 0.5 wt% to about 5 wt% based on the total weight of the unit dose, preferably from 1 wt% to about 2 wt% based on the total weight of the unit dose.

[0095] A unit dose of a feed additive composition or feed supplement composition may contain 0.03 mmol to 0.12 mmol of iodized salt, preferably 0.048 mmol to 0.09 mmol of iodized salt, more preferably 0.048 mmol to 0.072 mmol of iodized salt.

[0096] The feed additive composition or feed supplement composition may contain, per unit dose, iodized salt in an amount of about 0.5 wt% to about 15 wt% based on the total weight of the unit dose, preferably about 0.5 wt% to about 5 wt%, more preferably about 1 wt% to about 2 wt%, for example about 1 wt% to about 1.5 wt%.

[0097] Suitably, the feed additive composition or feed supplement composition contains 0.03 mmol to 0.12 mmol of iodized salt per unit dose, preferably 0.048 mmol to 0.09 mmol of iodized salt, more preferably 0.048 mmol to 0.072 mmol of iodized salt, and the iodized salt content is from about 0.5 wt% to about 5 wt% of the total weight per unit dose, preferably from 1 wt% to about 2 wt% of the total weight per unit dose.

[0098] For example, a unit dose of a feed additive composition or feed supplement composition may contain 5 to 20 mg of lactoperoxidase and 0.03 mmol to 0.12 mmol of iodized salt, wherein the lactoperoxidase content is from about 0.5 wt% to about 5 wt% of the total weight of the unit dose, and wherein the iodized salt content is from about 0.5 wt% to about 5 wt% of the total mass of the unit dose.

[0099] In a particularly preferred aspect, the feed additive composition or feed supplement composition comprises 8 to 15 mg of lactoperoxidase and 0.048 mmol to 0.09 mmol of iodized salt per unit dose, wherein the lactoperoxidase content is from about 0.5 wt% to about 5 wt% (even more preferably from about 1 wt% to about 2 wt%) based on the total weight of the unit dose, and wherein the iodized salt content is from about 0.5 wt% to about 5 wt% (even more preferably from about 1 wt% to about 2 wt%) based on the total mass of the unit dose.

[0100] Appropriately, the feed additive composition or feed supplement composition contains one or more of the following: flavoring agent, sweetener, and coloring agent.

[0101] The number of unit doses of the feed additive composition to be applied will depend on the total dose for the animal (e.g., an equine). For example, if a total dose of at least 80 mg of lactoperoxidase and 80 mg of iodized salt is required, and the unit dose of the feed additive composition contains 8 mg of lactoperoxidase and 8 mg of iodized salt, then 10 unit doses of the feed additive composition need to be applied to achieve the required total dose (80 mg LPO and 80 mg of iodized salt, such as KI).

[0102] Optionally, the feed additive composition contains about 8 mg to about 12 mg per unit dose of lactoperoxidase at a content of about 0.5 wt% to about 5 wt% based on the total weight of the unit dose, the iodized salt is potassium iodide at a content of about 8 mg to about 12 mg at a content of about 0.5 wt% to about 5 wt% based on the total weight of the unit dose, and the composition optionally contains vitamin C and optionally contains zinc oxide, and is administered at least 6 unit doses daily, optionally at least 8 unit doses daily, preferably at least 10 unit doses daily.

[0103] The present invention provides a composition, for example a pharmaceutical composition for treating wet mouth disease in lambs, the composition comprising lactoperoxidase, iodized salt and a pharmaceutically acceptable carrier and / or excipient, wherein the composition does not contain peroxide or peroxide source, and wherein the composition does not contain thiocyanate or thiocyanate source.

[0104] The composition may contain lactoperoxidase and iodized salt in a weight ratio of 1:10 to 10:1, preferably 1:3 to 3:1, and most preferably 1:1.3 to 1.3:1.

[0105] Iodized salt may be selected, for example, from sodium iodide, potassium iodide, lithium iodide, ammonium iodide, calcium iodide, cesium iodide, hydrogen iodide, rhodium iodide, and combinations thereof, with sodium iodide and / or potassium iodide being preferred, and potassium iodide being more preferred.

[0106] Suitablely, the treatment (WMD in lambs) comprises administering at least 8 mg of lactoperoxidase and at least 0.048 mmol of iodized salt to the lamb. Preferably, the treatment comprises administering at least 10 mg of lactoperoxidase and at least 0.060 mmol of iodized salt to the lamb. Suitablely, the composition of the invention is administered within 48 hours after birth, preferably within 12 hours after birth, more preferably within 6 hours after birth, most preferably within 3 hours after birth, for example within 2 hours after birth.

[0107] The treatment may include administering 8 mg to 200 mg of lactoperoxidase to the lamb, preferably 8 mg to 100 mg of lactoperoxidase, more preferably 8 mg to 50 mg of lactoperoxidase, for example 8 mg to 20 mg of lactoperoxidase, preferably 8 mg to 12 mg of lactoperoxidase.

[0108] The treatment may include administering 0.048 mmol to 1.2 mmol of iodized salt to the lamb, preferably 0.048 mmol to 0.6 mmol of iodized salt, more preferably 0.048 mmol to 0.3 mmol of iodized salt, such as 0.048 to 0.12 mmol of iodized salt, preferably 0.048 mmol to 0.072 mmol of iodized salt.

[0109] Suitablely, the treatment comprises administering to the lamb 8 mg to 200 mg of lactoperoxidase, preferably 8 mg to 100 mg of lactoperoxidase, more preferably 8 mg to 50 mg of lactoperoxidase, such as 8 mg to 20 mg of lactoperoxidase, and administering to the lamb 0.048 mmol to 1.2 mmol of iodized salt, preferably 0.048 mmol to 0.6 mmol of iodized salt, more preferably 0.048 mmol to 0.3 mmol of iodized salt, such as 0.048 to 0.12 mmol of iodized salt, most preferably 0.048 mmol to 0.072 mmol of iodized salt.

[0110] For example, treatment may include administering 8 mg to 200 mg of lactoperoxidase and 0.048 mmol to 1.2 mmol of iodized salt to the lamb. The treatment may include administering 8 mg to 100 mg of lactoperoxidase and 0.048 mmol to 0.6 mmol of iodized salt to the lamb, preferably 8 g to 50 mg of lactoperoxidase and about 0.048 mmol to 0.3 mmol of iodized salt, such as 8 mg to 20 mg of lactoperoxidase and 0.048 mmol to 0.12 mmol of iodized salt.

[0111] This invention discloses a composition for treating wet mouth disease in lambs, such as a pharmaceutically acceptable composition comprising lactoperoxidase, iodized salt, and a pharmaceutically acceptable carrier and / or excipient, wherein the composition does not contain peroxide or peroxide source, and wherein the composition does not contain thiocyanate or thiocyanate source, wherein the lactoperoxidase content is at least 8 mg and the iodized salt content is at least 0.048 mmol.

[0112] The composition may contain 8 mg to 200 mg of lactoperoxidase administered to lambs, preferably 8 mg to 100 mg of lactoperoxide, more preferably 8 mg to 50 mg of lactoperoxide, such as 8 mg to 20 mg of lactoperoxidase, and most preferably 8 mg and 12 mg of lactoperoxidase.

[0113] The composition may contain 0.048 mmol to 1.2 mmol of iodized salt applied to lambs, preferably 0.048 mmol to 0.6 mmol of iodized salt, more preferably 0.048 mmol to 0.3 mmol of iodized salt, for example 0.048 to 0.12 mmol of iodized salt, and most preferably 0.048 mmol to 0.072 mmol of iodized salt.

[0114] Suitablely, the composition comprises 8 mg to 200 mg of lactoperoxidase and 0.048 mmol to 1.2 mmol of iodized salt, preferably 8 mg to 100 mg of lactoperoxidase and 0.048 mmol to 0.6 mmol of iodized salt, more preferably 8 mg to 50 mg of lactoperoxidase and 0.048 mmol to 0.3 mmol of iodized salt, for example 8 mg to 20 mg of lactoperoxidase and 0.048 mmol / 0.12 mmol of iodized salt.

[0115] The composition used is suitable for administration within 48 hours after birth of lambs, preferably within 12 hours after birth, more preferably within 6 hours after birth, and most preferably within 3 hours after birth.

[0116] Therefore, the present invention also provides a method for treating wet mouth disease in lambs, comprising administering the composition disclosed herein to the lambs preferably within 48 hours after birth.

[0117] The composition may be provided in unit dosage forms, preferably solid dosage forms, such as tablets, or powder dosage forms, such as powders. It should be understood that the number of unit doses to be administered is determined by the required therapeutic amount. For example, to provide a treatment of 8 mg LPO and 8 mg KI, a unit dose containing 8 mg LPO and 8 mg potassium iodide is required; to provide a treatment of 16 mg LPO and 16 mg KI, two unit doses are required, each containing 8 mg LPO and 8 mg KI.

[0118] The content of lactoperoxidase can be from 0.5 mg to 200 mg, for example from 1 mg to 150 mg, preferably from 1 mg to 100 mg. For example, a unit dose of the pharmaceutical composition may contain 0.5 mg to 200 mg of lactoperoxidase, for example from 1 mg to 150 mg, preferably from 1 mg to 100 mg.

[0119] The iodized salt content can be from 0.5 mg to 200 mg, for example, from 1 mg to 100 mg, preferably from 5 mg to 50 mg, more preferably from 8 mg to 20 mg, for example, from 8 mg to 12 mg. For example, a unit dose of the pharmaceutical composition can contain 0.5 mg to 200 mg, for example, from 1 mg to 100 mg, preferably from 5 mg to 50 mg, more preferably from 8 mg to 20 mg, for example, from 8 mg to 12 mg of iodized salt.

[0120] The content of lactoperoxidase is from about 0.5 wt% to about 15 wt% based on the total weight of the composition, preferably from about 0.5 wt% to about 5 wt%, more preferably from about 1 wt% to about 2 wt%, for example from about 1 wt% to about 1.5 wt%.

[0121] Iodized salt, preferably potassium iodide, is present in a content of about 0.5 wt% to about 15 wt% based on the total weight of the composition, preferably about 0.5 wt% to about 5 wt%, more preferably about 1 wt% to about 2 wt%, for example about 1 wt% to about 1.5 wt%.

[0122] Preferably, the composition is formulated for oral administration. Preferably, the composition is formulated as a tablet.

[0123] Appropriately, treatment includes administering the pharmaceutical composition within 48 hours of birth, preferably within 12 hours of birth, and most preferably within 6 hours of birth.

[0124] Preferably, the composition comprises 8 to 12 mg of lactoperoxidase and 8 to 12 mg of iodized salt.

[0125] Suitable, the composition further does not contain oxidizing agents, such as inorganic oxidizing agents, for example periodic acid or its salts.

[0126] Suitablely, the present invention provides a composition, for example a pharmaceutical composition for treating wet mouth disease in lambs, the composition comprising lactoperoxidase, iodized salt, and a pharmaceutically acceptable carrier and / or excipient, wherein the iodized salt is preferably sodium iodide or potassium iodide, wherein the lactoperoxidase content is 8 to 20 mg, preferably 8 to 12 mg, and wherein the iodized salt content is 0.048 mmol to 0.12 mmol, preferably 0.048 mmol to 0.072 mmol, wherein the composition does not contain peroxide or peroxide source, and wherein the composition does not contain thiocyanate or thiocyanate source.

[0127] For example, the present invention provides a composition, such as a pharmaceutical composition for treating wet mouth disease in lambs, the composition comprising lactoperoxidase, potassium iodide and a pharmaceutically acceptable carrier and / or excipient, wherein the lactoperoxidase content is 8 to 20 mg, preferably 8 to 12 mg, the potassium iodide content is 8 mg to 20 mg, preferably 8 mg to 12 mg, wherein the composition is free of peroxides or peroxide sources, and wherein the composition is free of thiocyanate or thiocyanate sources.

[0128] Optionally, the composition is administered within 48 hours after birth, preferably within 12 hours after birth, and most preferably within 6 hours after birth.

[0129] The present invention also provides a pharmaceutical composition for treating swine diarrhea or scour, the composition comprising lactoperoxidase, iodized salt, and a pharmaceutically acceptable carrier and / or excipient, wherein the composition does not contain peroxide or peroxide source, and wherein the composition does not contain thiocyanate or thiocyanate source. Swine may suffer from Escherichia coli infection.

[0130] The pharmaceutical composition may contain lactoperoxidase and iodized salt in a weight ratio of 1:10 to 10:1, preferably 1:3 to 3:1, most preferably 1:1.3 to 1.3:1, for example about 1:1.

[0131] Iodized salt may be selected, for example, from sodium iodide, potassium iodide, lithium iodide, ammonium iodide, calcium iodide, cesium iodide, hydrogen iodide, rhodium iodide, and combinations thereof, with sodium iodide and / or potassium iodide being preferred, and potassium iodide being more preferred.

[0132] The pharmaceutical composition may be provided in unit dosage form, preferably in solid dosage form, such as powder dosage form.

[0133] Treatment appropriately comprises administering to pigs at least 8 mg of lactoperoxidase and at least 0.048 mmol of iodized salt daily (post-weaning). Preferably, treatment comprises administering to pigs at least 10 mg of lactoperoxidase and at least 0.060 mmol of iodized salt daily. Preferably, treatment comprises administering to pigs at least 20 mg of lactoperoxidase and at least 0.12 mmol of iodized salt daily. Appropriately, the composition of the present invention is administered daily post-weaning (i.e., once the pig has ceased suckling), for 7 days, optionally for 14 days.

[0134] For example, treatment may include daily administration of 10 mg to 200 mg of lactoperoxidase, such as 10 mg to 100 mg daily, preferably 10 mg to 50 mg. For example, daily from day 1 to day 7 or from day 1 to day 14 after weaning.

[0135] For example, treatment may include daily administration of 0.006 mmol to 1.2 mmol of iodized salt, such as 0.006 mmol to 0.6 mmol daily, preferably 0.006 mmol to 0.3 mmol. For example, from day 1 to day 7 or from day 1 to day 14 after weaning.

[0136] Preferably, the composition is formulated for oral administration. Preferably, the composition is formulated as a powder.

[0137] Appropriately, the composition is used for weaned pigs, i.e., once the pigs have stopped suckling their mother's milk.

[0138] Appropriately, treatment may involve applying the composition to pigs that are at least 28 days old.

[0139] Appropriately, the treatment comprises administering the composition to the pigs daily. Preferably, the treatment comprises administering the drug composition to the pigs daily for at least 14 days.

[0140] Preferably, the composition comprises 8 to 50 mg of lactoperoxidase and 8 to 50 mg of potassium iodide. More preferably, it comprises 10 to 40 mg of lactoperoxidase and 10 to 40 mg of potassium iodide.

[0141] The composition can be provided in unit dosage forms. Unit dosage forms can be solid formulations, such as tablets or powders, or liquid formulations, including suspensions. Preferably, the unit dosage form is a powder or liquid formulation, which advantageously can be added to the pig's feed / water, making administration easier than direct application.

[0142] The unit dose of the composition for treating swine diarrhea or scour suitably contains 0.5 mg to 200 mg, for example 1 mg to 100 mg, preferably 8 mg to 50 mg of lactoperoxidase.

[0143] The unit dose of the composition for treating swine diarrhea or scour suitably contains 0.003 mmol to 1.2 mmol, for example 0.006 mmol to 0.6 mmol, preferably 0.048 mmol to 0.3 mmol of iodized salt.

[0144] Suitably, the unit dose of the composition for treating swine diarrhea or scour comprises 0.5 mg to 200 mg of lactoperoxidase and 0.003 mmol to 1.2 mmol of iodized salt. For example, the unit dose of the composition comprises 1 mg to 100 mg of lactoperoxidase and 0.006 mmol to 0.6 mmol of iodized salt. Preferably, the unit dose of the composition comprises 8 mg to 50 mg of lactoperoxidase and 0.048 mmol to 0.3 mmol of iodized salt.

[0145] It should be understood that the number of unit doses to be administered is determined by the required therapeutic dose. For example, to provide a treatment dose of 8 mg LPO and 8 mg KI, a single unit dose containing 8 mg LPO and 8 mg potassium iodide is required. To provide a treatment dose of 16 mg LPO and 16 mg KI, two unit doses are required, each containing 8 mg LPO and 8 mg KI. To provide a (daily) therapeutic dose of 20 mg LPO and 20 mg KI, a single unit dose containing 20 mg LPO and 20 mg potassium iodide is required (daily treatment).

[0146] Suitable, the composition further does not contain oxidizing agents, such as inorganic oxidizing agents, for example periodic acid or its salts.

[0147] Suitable, the composition is applied daily after weaning (e.g., at least 28 days old) for at least 7 days, preferably at least 14 days.

[0148] The present invention also provides a composition, such as a pharmaceutical composition, for treating diarrhea or scour in calves, preferably dairy calves, said composition comprising lactoperoxidase, iodized salt and a pharmaceutically acceptable carrier and / or excipient, said composition not containing peroxide or peroxide source, and said component not containing thiocyanate or thiocyanate source.

[0149] The composition may contain lactoperoxidase and iodized salt in a weight ratio of 1:10 to 10:1, preferably 1:3 to 3:1, most preferably 1:1.3 to 1.3:1, for example about 1:1.

[0150] Iodized salt may be selected, for example, from sodium iodide, potassium iodide, lithium iodide, ammonium iodide, calcium iodide, cesium iodide, hydrogen iodide, rhodium iodide, and combinations thereof, with sodium iodide and / or potassium iodide being preferred, and potassium iodide being more preferred.

[0151] Treatment appropriately comprises administering at least 8 mg of lactoperoxidase and at least 0.048 mmol of iodized salt to the calf daily. Preferably, treatment comprises administering at least 10 mg of lactoperoxidase and at least 0.060 mmol of iodized salt to the calf daily. Appropriately, the composition of the present invention is administered from the first day to the seventh day (day 1 to day 7) of the calf's life, preferably from day 1 to day 30, more preferably from day 1 to day 60.

[0152] For example, treatment may include administering 10 mg to 200 mg of lactoperoxidase daily, such as 10 mg to 100 mg daily, preferably 10 mg to 50 mg. For example, from day 1 to day 7, or from day 1 to day 30, or from day 1 to day 60.

[0153] For example, treatment may include administering 0.006 mmol to 1.2 mmol of iodized salt daily, such as 0.006 mmol to 0.6 mmol daily, preferably 0.006 mmol to 0.3 mmol. For example, from day 1 to day 7, or from day 1 to day 30, or from day 1 to day 60.

[0154] The pharmaceutical composition may be provided in unit dosage forms. The unit dosage form may be a solid dosage form, such as a tablet or powder, or a liquid dosage form, including a suspension. Preferably, the unit dosage form is a powder or liquid dosage form, which advantageously can be added to calf milk, thereby making administration easier than direct administration.

[0155] The unit dose of the composition may contain 0.5 mg to 200 mg of lactoperoxidase, for example 1 mg to 100 mg, preferably 8 mg to 50 mg, more preferably 8 mg to 20 mg of lactoperoxidase.

[0156] The unit dose of the composition may contain iodized salt in a content of 0.003 mmol to 1.2 mmol, for example 0.006 mmol to 0.6 mmol, preferably 0.048 mmol to 0.3 mmol, more preferably 0.048 mmol to 0.12 mmol.

[0157] Appropriately, each unit dose may contain 8 mg to 20 mg of lactoperoxidase and 0.048 mmol to 0.3 mmol of iodized salt. For example, each unit dose may contain 8 mg to 20 mg of lactoperoxidase and 8 mg to 20 mg of potassium iodide.

[0158] It should be understood that the number of unit doses to be administered is determined by the required therapeutic dose. For example, to provide treatment with 8 mg LPO and 8 mg KI, a single unit dose containing 8 mg LPO and 8 mg potassium iodide is required; to provide treatment with 16 mg LPO and 16 mg KI, two unit doses are required, each containing 8 mg LPO and 8 mg KI.

[0159] Suitable, the composition further does not contain oxidizing agents, such as inorganic oxidizing agents, for example periodic acid or its salts.

[0160] Appropriately, the composition is applied to calves, preferably dairy calves, once daily, for example, once daily for the first 7 days after their birth, preferably once daily for the first 30 days after their birth, and more preferably once daily for the first 60 days after their birth.

[0161] Appropriately, the treatment comprises administering the composition to the calf daily. Preferably, the treatment comprises administering the composition to the calf once daily from 1 to 7 days of age, more preferably from 1 to 30 days of age, and even more preferably from 1 to 60 days of age.

[0162] In a particularly preferred embodiment, the composition for treating diarrhea or scour in calves comprises 8 to 12 mg of lactoperoxidase and 8 to 12 mg of potassium iodide.

[0163] The present invention further provides a pharmaceutical composition comprising lactoperoxidase, iodized salt, and a pharmaceutically acceptable carrier and / or excipient, wherein the composition does not contain peroxide or peroxide source, and wherein the composition does not contain thiocyanate or thiocyanate source, for the treatment or prevention of gastrointestinal bacterial infections in mammals.

[0164] The pharmaceutical composition may contain lactoperoxidase and iodized salt in a weight ratio of 1:10 to 10:1, preferably 1:3 to 3:1, most preferably 1:1.3 to 1.3:1, for example about 1:1.

[0165] Iodized salt may be selected, for example, from sodium iodide, potassium iodide, lithium iodide, ammonium iodide, calcium iodide, cesium iodide, hydrogen iodide, rhodium iodide, and combinations thereof, with sodium iodide and / or potassium iodide being preferred, and potassium iodide being more preferred.

[0166] The pharmaceutical composition may be provided in unit dosage form, preferably in solid dosage form, such as tablets, or in powder form, such as powder.

[0167] The content of lactoperoxidase is from 0.5 mg to 200 mg, for example from 1 mg to 150 mg, preferably from 1 mg to 100 mg. For example, a unit dose of the pharmaceutical composition may contain 0.5 mg to 200 mg, for example from 1 mg to 150 mg, preferably from 1 mg to 100 mg of lactoperoxidase.

[0168] The iodized salt contains 0.003 mmol to 1.2 mmol, for example 0.006 mmol to 0.6 mmol, preferably 0.03 mmol to 0.3 mmol, more preferably 0.048 mmol to 0.12 mmol, for example 0.048 mmol to 0.072 mmol.

[0169] The iodized salt contains 0.5 mg to 200 mg, for example 1 mg to 100 mg, preferably 5 mg to 50 mg, more preferably 8 mg to 20 mg, for example 8 mg to 12 mg. For example, a unit dose of the pharmaceutical composition may contain 0.5 mg to 200 mg, for example 1 mg to 100 mg, preferably 5 mg to 50 mg, more preferably 8 mg to 20 mg, for example 8 mg to 12 mg of iodized salt.

[0170] The content of lactoperoxidase is from about 0.5 wt% to about 15 wt% based on the total weight of the composition, preferably from about 0.5 wt% to about 5 wt%, more preferably from about 1 wt% to about 2 wt%, for example from about 1 wt% to about 1.5 wt%.

[0171] Iodized salt, preferably potassium iodide, is present in a content of about 0.5 wt% to about 15 wt% based on the total weight of the composition, preferably about 0.5 wt% to about 5 wt%, more preferably about 1 wt% to about 2 wt%, for example about 1 wt% to about 1.5 wt%.

[0172] Suitable, the composition further does not contain oxidizing agents, such as inorganic oxidizing agents, for example periodic acid or its salts.

[0173] The composition can be formulated for oral administration.

[0174] The bacterial infection may be caused by intestinal bacteria.

[0175] Bacterial infection could be caused by Escherichia coli or Salmonella, or by Streptococcus, such as Streptococcus equi.

[0176] Mammals can be sheep, pigs, horses, cats, dogs, or humans.

[0177] Appropriately, mammals are monogastric mammals.

[0178] Mammals may be lambs infected with E. coli, for example, lambs may have wet mouth disease.

[0179] The mammal could be a pig. For example, a pig could be infected with E. coli. The pig in question may be infected with intestinal E. coli.

[0180] The mammal could be a horse. For example, a horse could be infected with E. coli and / or Streptococcus equi. A horse could also have EGUS, such as EGSD and / or EGGD.

[0181] In another aspect, the present invention provides a feed additive or feed supplement composition comprising: Lactoperoxidase and iodized salt, wherein the composition does not contain peroxide or peroxide source, and wherein the mixture does not contain thiocyanate or thiocyanate source.

[0182] In another aspect, the present invention provides an animal feed comprising the feed additive or feed supplement composition described herein.

[0183] In another aspect, the present invention provides the compositions described herein for treating gastric ulcers, particularly gastric ulcers in dogs, cats, and equines (e.g., horses).

[0184] The present invention also provides a composition for oral administration, such as a pharmaceutical composition, comprising: lactoperoxidase, iodized salt, and a pharmaceutically acceptable carrier and / or excipient, wherein the composition does not contain peroxide or peroxide source; and wherein the composition does not contain thiocyanate or thiocyanate source; wherein the weight ratio of lactoperoxidase to iodized salt is in the range of 1:1.3 to 1.3:1.

[0185] Iodized salt can be selected from sodium iodide, potassium iodide, lithium iodide, ammonium iodide, calcium iodide, cesium iodide, hydrogen iodide, rhodium iodide, and combinations thereof, with sodium iodide and / or potassium iodide being preferred, and potassium iodide being more preferred.

[0186] Suitable, the composition further does not contain oxidizing agents, such as inorganic acids, for example periodic acid or its salts.

[0187] The composition can be formulated into solid doses, such as tablets or powders, or into liquid doses, such as suspensions.

[0188] Preferably, the composition comprises two or more excipients. For example, the composition may comprise two or more of magnesium stearate, lactose, glucose, microcrystalline cellulose, starch (corn), silicon dioxide, titanium dioxide, zinc oxide, colostrum, hydroxypropyl methylcellulose, stearic acid, sodium starch glycolate, gelatin, talc, sucrose, calcium stearate, and povidone. For example, a pharmaceutical composition may comprise magnesium stearate, microcrystalline cellulose, and colostrum. Optionally, the composition further comprises zinc oxide.

[0189] Suitable, the composition comprises one or more of the following: flavoring agents, sweeteners, and colorings.

[0190] The content of lactoperoxidase is from 0.5 mg to 200 mg, for example from 1 mg to 150 mg, preferably from 1 mg to 100 mg.

[0191] The iodized salt content is from 0.003 mmol to 1.2 mmol, for example from 0.006 mmol to 1.2 mmol, for example from 0.006 mmol to 0.9 mmol, preferably from 0.006 mmol to 0.6 mmol. For example, the iodized salt content is from 0.5 mg to 200 mg, for example from 1 mg to 150 mg, preferably from 1 mg to 100 mg.

[0192] The composition is formulated in unit doses. Suitablely, one or more unit doses of the composition may be administered.

[0193] Suitablely, the unit dose of the composition may contain 5 to 20 mg of lactoperoxidase, preferably 8 to 15 mg of lactoperoxidase, more preferably 8 to 12 mg of lactoperoxidase.

[0194] Suitable, the composition per unit dose may contain 0.03 mmol to 0.12 mmol of iodized salt, preferably 0.048 mmol to 0.09 mmol of iodized salt, more preferably 0.048 mmol to 0.072 mmol of iodized salt.

[0195] For example, the unit dose of the composition may contain 5 mg to 20 mg of iodized salt, preferably 8 mg to 15 mg of iodized salt, more preferably 8 mg to 12 mg of iodized salt.

[0196] Suitable, the composition per unit dose contains 5 to 20 mg of lactoperoxidase, preferably 8 to 15 mg of lactoperoxidase, more preferably 8 to 12 mg of lactoperoxidase, and 0.03 mmol to 0.12 mmol of iodized salt, preferably 0.048 mmol to 0.09 mmol of iodized salt, more preferably 0.048 mmol to 0.072 mmol of iodized salt.

[0197] The content of lactoperoxidase is from about 0.5 to about 5 wt% of the total weight per unit dose, preferably from about 1 wt% to about 2 wt%, more preferably from about 1 wt% to about 1.5 wt%.

[0198] The iodized salt content is about 0.5 to about 5 wt% based on the total weight per unit dose, preferably about 1 wt% to about 2 wt%, more preferably about 1 wt% to about 1.5 wt%.

[0199] The oral administration composition can be administered in multiple unit doses. Suitablely, the composition can be administered daily in multiple unit doses.

[0200] Understandably, the number of unit doses to be administered is determined by the overall treatment to be provided. definition

[0201] Before further description, certain terms used in the specification, embodiments, and appended claims are collected herein. These definitions should be read in conjunction with the remainder of this disclosure and will be understood by those skilled in the art. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art.

[0202] As used herein, the terms “pharmaceutically acceptable carrier” or “pharmaceutically acceptable excipient” refer to any of the following: solvent, dispersion medium, coating, isotonic agent, and absorption delay agent, provided that they are compatible with drug administration. Those skilled in the art are familiar with the use of carriers and excipients for pharmaceutically active substances. Each carrier must be “acceptable,” meaning it is compatible with the test composition and its components and is harmless to the patient. Some examples of materials that can be used as pharmaceutically acceptable carriers include: (1) sugars, such as lactose, glucose, and sucrose; (2) starches, such as corn starch and potato starch; (3) cellulose and its derivatives, such as sodium carboxymethyl cellulose, ethyl cellulose, and cellulose acetate; (4) astragalus powder; (5) malt; (6) gelatin; (7) talc; (8) excipients, such as cocoa butter and suppository waxes; (9) oils, such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil, and soybean oil. (10) Diols, such as propylene glycol; (11) Polyols, such as glycerol, sorbitol, mannitol and polyethylene glycol; (12) Esters, such as ethyl oleate and ethyl laurate; (13) Agar; (14) Buffers, such as magnesium hydroxide and aluminum hydroxide; (15) Alginate; (16) Atherless water; (17) Isotonic saline; (18) Ringer's solution; (19) Ethanol; (20) Phosphate buffer solution; (21) Water; and (22) Other non-toxic and compatible substances used in pharmaceutical preparations.

[0203] In addition, the composition may contain other active compounds to provide supplemental, additional, or enhanced therapeutic functions.

[0204] As used herein, the term "pharmaceutical composition" refers to a composition comprising lactoperoxidase and iodized salt, as disclosed herein, formulated with one or more pharmaceutically acceptable carriers, wherein the composition does not contain hydrogen peroxide or a source of hydrogen peroxide.

[0205] The compositions of the present invention are for oral administration and therefore can be formulated into tablets, capsules, granules, powders, syrups, suspensions, liquids, effervescent tablets, etc. These formulations can be prepared by conventional methods, and the compositions can be mixed with any conventional additives, such as excipients, binders, disintegrants, lubricants, flavoring agents, solubilizers, suspending agents, emulsifiers, or coating agents, if desired.

[0206] The compositions of the present invention may include wetting agents, emulsifiers and lubricants, such as sodium dodecyl sulfate and magnesium stearate, as well as colorants, release agents, coating agents, sweeteners, flavoring agents and flavoring agents, and preservatives and antioxidants may be present in the formulation.

[0207] Formulations of the compounds and pharmaceutical compositions of the present invention suitable for oral administration may be capsules, sachets, pills, tablets, lozenges (using flavoring agents, typically sucrose and gum arabic or tragacanth), powders, granules, or as solutions or suspensions in aqueous or non-aqueous liquids, or as oil-in-water or water-in-oil emulsions, or as elixirs or syrups, or as lozenges (using inert matrices such as gelatin and glycerin, or sucrose and gum arabic), each formulation containing a predetermined amount of the target composition as the active ingredient. The compositions of the present invention may also be administered as pills, ointments, or pastes.

[0208] In oral solid dosage forms (capsules, tablets, pills, film-coated tablets, sugar-coated tablets, powders, granules, etc.), the test composition is mixed with one or more pharmaceutically acceptable carriers (such as sodium citrate or dicalcium phosphate) and / or any of the following: (a) fillers or extenders, such as sucrose, glucose, mannitol, starch, lactose, and / or silica; (b) binders, such as carboxymethyl cellulose, alginate, gelatin, polyvinylpyrrolidone, sucrose, and / or gum arabic; (c) preservatives. (d) Wetting agents, such as glycerin; (e) disintegrants, such as agar, calcium carbonate, potato or cassava starch, alginate, certain silicates, and sodium carbonate; (f) solution retarder, such as paraffin; (g) absorption promoters, such as quaternary ammonium compounds; (h) wetting agents, such as acetyl alcohol and glyceryl monostearate; (i) absorbents, such as kaolin and bentonite; (j) lubricants, such as talc, calcium stearate, magnesium stearate, solid polyethylene glycol, sodium dodecyl sulfate, and mixtures thereof; and (j) colorants. In the case of capsules, tablets, and pills, the composition may also contain a buffer. Similar types of solid compositions may also be used as fillers in soft-filled and hard-filled gelatin capsules, using lactose or lactose, and excipients such as high molecular weight polyethylene glycol.

[0209] Formulations and compositions may include micronized crystals of the disclosed compounds.

[0210] Tablets can be made by compression or molding, optionally with the addition of one or more excipients. Compressed tablets can be prepared using binders (e.g., gelatin or hydroxypropyl methylcellulose), lubricants, inert diluents, preservatives, disintegrants (e.g., sodium starch glycolate or croscarmellose sodium), surfactants, or dispersants. Molded tablets can be prepared by molding a mixture of the compositions of the invention wetted with an inert liquid diluent in a suitable machine. Tablets and other solid dosage forms, such as film-coated or sugar-coated tablets, capsules, pills, and granules, can optionally be scored or prepared with coatings and shells, such as enteric coatings and other coatings well known in the field of pharmaceutical formulations.

[0211] Orally administered liquid dosage forms include pharmaceutically acceptable emulsions, microemulsions, solutions, suspensions, syrups, and elixirs. In addition to the subject composition, liquid dosage forms may also contain inert diluents commonly used in the art, such as water or other solvents, solubilizers, and emulsifiers, such as ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butanediol, oils (particularly cottonseed oil, peanut oil, corn oil, germ oil, olive oil, castor oil, and sesame oil), glycerin, tetrahydrofurfuryl alcohol, polyethylene glycol and sorbitol fatty acid esters, cyclodextrins, and mixtures thereof.

[0212] In addition to the main composition, the suspension may also contain suspending agents such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol and polyoxyethylene sorbitol esters, microcrystalline cellulose, aluminum hydroxide, bentonite, agar and tragacanth gum, and mixtures thereof.

[0213] Throughout this specification, when a composition is described as having, including, or comprising a specific component, it is conceivable that the composition is also substantially composed of or consisting of said component. Similarly, when a process is described as having, including, or comprising specific process steps, these processes are also substantially composed of or consisting of said process steps. Unless otherwise stated, the order of steps or the sequence of certain actions is irrelevant as long as the invention remains operable. Furthermore, unless otherwise stated, two or more steps or actions may be performed simultaneously. Detailed Implementation

[0214] As described above, the present invention provides a pharmaceutical composition, combination, and / or feed additive / supplement for treating equine gastric ulcer syndrome, said composition comprising: lactoperoxidase, iodized salt, and a pharmaceutically acceptable carrier and / or excipient. Suitably, said composition does not contain peroxides or peroxide sources, and said composition does not contain thiocyanate or thiocyanate sources. Optionally, said composition further does not contain oxidizing agents, such as inorganic oxidizing agents, for example periodic acid or its salts. A method of treating equine gastric ulcer syndrome is also described, comprising administering the composition described herein to an equine in need, said composition comprising lactoperoxidase, iodized salt, and a pharmaceutically acceptable carrier and / or excipient.

[0215] The present invention further provides a pharmaceutical composition, combination, and / or feed additive / feed supplement for treating wet mouth disease in lambs, said composition comprising: lactoperoxidase, iodized salt, and a pharmaceutically acceptable carrier and / or excipient. The composition does not contain peroxides or peroxide sources, nor does it contain thiocyanate or thiocyanate sources. Suitably, the composition further does not contain oxidizing agents, such as inorganic oxidizing agents, for example periodic acid or its salts. A method of treating wet mouth disease in lambs is also described, comprising administering the composition described herein to lambs in need, said composition comprising lactoperoxidase, iodized salt, and a pharmaceutically acceptable carrier and / or excipient.

[0216] This invention also provides a pharmaceutical composition, combination, and / or feed additive / supplement for treating swine diarrhea or scour, said composition comprising: lactoperoxidase, iodized salt, and a pharmaceutically acceptable carrier and / or excipient. The composition does not contain peroxide or peroxide source, nor does it contain thiocyanate or thiocyanate source. Suitably, the composition further does not contain oxidizing agents, such as inorganic oxidizing agents, for example, periodic acid or a salt thereof. Suitably, the swine has Escherichia coli infection. This invention also describes a method for treating swine diarrhea or scour, comprising administering the composition described herein to swine (suitably, newly weaned swine (e.g., 28 days old, no longer suckling, if necessary)) the composition comprising lactoperoxidase, iodized salt, and a pharmaceutically acceptable carrier and / or excipient.

[0217] This invention also provides a pharmaceutical composition, combination, and / or feed additive / feed supplement for treating calf diarrhea or scour, preferably in dairy calves, said composition comprising: lactoperoxidase, iodized salt, and a pharmaceutically acceptable carrier and / or excipient. The composition does not contain peroxides or peroxide sources, nor does it contain thiocyanate or thiocyanate sources. Suitably, the composition further does not contain oxidizing agents, such as inorganic oxidizing agents, for example, periodic acid or its salts. This invention also discloses a method for treating calf diarrhea or scour, preferably in dairy calves, comprising administering to the calf in need the composition described herein, said composition comprising: lactoperoxidase, iodized salt, and a pharmaceutically acceptable carrier and / or excipient.

[0218] Furthermore, the present invention provides a pharmaceutical composition, combination, and / or feed additive / feed supplement comprising: lactoperoxidase, iodized salt, and a pharmaceutically acceptable carrier and / or excipient, wherein the composition does not contain a peroxide or a peroxide source, and wherein the composition also does not contain a thiocyanate or a thiocyanate source. Suitably, the composition further does not contain an oxidizing agent, such as an inorganic oxidizing agent, for example periodic acid or a salt thereof. The composition can be used to treat, prevent, and reduce the effects of gastrointestinal bacterial infections in mammals such as horses, lambs, pigs, calves, cats, dogs, and humans. Suitably, the gastrointestinal bacterial infection is an Escherichia coli or Streptococcus infection. The compositions of the present invention can be used for prophylactic treatment in mammals.

[0219] Although the lactoperoxidase system can be used to preserve milk and in other applications such as mouthwash and disinfectants, its use as a therapeutic agent in mammals is limited, particularly in monogastric mammals. This is partly due to the requirement of hydrogen peroxide, or a peroxide source, for the lactoperoxidase system to function.

[0220] As mentioned above, the lactoperoxidase system involves a combination of lactoperoxidase, thiocyanate ions or halide ions, and hydrogen peroxide or a hydrogen peroxide source. A major obstacle to the widespread adoption of lactoperoxidase systems for antibacterial therapy is the requirement for hydrogen peroxide.

[0221] Hydrogen peroxide is toxic to mammalian cells. It has three main mechanisms of toxicity: corrosive damage, oxygen formation, and lipid peroxidation. High concentrations of hydrogen peroxide are corrosive and can cause tissue damage. Ingestion of hydrogen peroxide leads to the production of large amounts of oxygen, a byproduct of its decomposition. This oxygen can enter the bloodstream, potentially causing venous or arterial gas embolism. It can also produce direct cytotoxic effects through lipid peroxidation, leading to tissue damage. Hydrogen peroxide generates oxygen free radicals, which have considerable physiological and pathological significance. Cell culture studies report cytotoxicity of hydrogen peroxide in concentrations ranging from 0.05 to 0.58 mmol / L (Rubin, R. and J. Farber (1984). "Mechanisms of the killing of cultured hepatocytes by hydrogen peroxide." ArchBiochem Biophys 228: 450-459; Ramp, W., R. Arnold, R. JE and J. Yancey (1987)). High concentrations of hydrogen peroxide can damage cell viability and reduce cell proliferation.

[0222] Advantageously, the present invention does not require exogenous hydrogen peroxide or another exogenous source of hydrogen peroxide. The compositions of the present invention do not contain peroxides or peroxide sources. For example, the compositions do not contain hydrogen peroxide or hydrogen peroxide derivatives. For example, the compositions do not contain oxidases, such as glucose oxidase, which would lead to the production of peroxides, such as hydrogen peroxide. The compositions of the present invention further do not contain oxidizing agents, such as inorganic oxidizing agents, such as periodic acid or its salts.

[0223] Several bacterial strains produce hydrogen peroxide, for example, to inhibit the growth of other microorganisms. Bacteria typically produce hydrogen peroxide under aerobic conditions.

[0224] Many areas of the mammalian body are potentially home to microorganisms that produce hydrogen peroxide. While some areas are inherently aerobic, thus allowing considerable levels of hydrogen peroxide to accumulate—such as the hydrogen peroxide produced by oral streptococci (Erttmann, S. and N. Gekara (2019) “Hydrogen peroxide release by bacteria suppresses inflammasome-dependent innate immunity” Nature Communications 10:3493)—anaerobic conditions are prevalent in many areas of the body where bacteria may be found, greatly reducing the capacity for hydrogen peroxide production and accumulation. This is especially true of the mammalian stomach.

[0225] For example, Fonty et al. (Fonty, G., P. Gouet, J.-P. Jouany and J.-P. Senaud (1987) "Establishment of the microflora and anaerobic fungi in the rumen of lambs" Journal of General Microbiology 133: 1835-1843) studied the development of the microbiome in lambs and sheep from birth. From birth to 2 days old, the lamb stomach was mainly colonized by strictly anaerobic bacteria, with a bacterial level of 10-1. 9 cfu / ml. During the first week of life, the number of strict anaerobes increases, while the total number of aerobic and facultative anaerobes decreases by 10-100 times.

[0226] Swords et al. (Swords, WE; Wu, CC; Champlin, FR; Buddington, RK) studied the microbiota of newborn piglets and noted that the number of aerobic bacteria increases in the first week after birth, during which time their numbers are significantly lower than those of anaerobic bacteria. Biol. Neon. 1993, 63, 191–200.

[0227] Therefore, the literature teaches that such an environment is not suitable for microbial-mediated hydrogen peroxide production.

[0228] The invention will be more easily understood by reviewing the following examples.

[0229] Lactoperoxidase is an enzyme whose activity is affected by many variables, including pH. Lactoperoxidase exhibits optimal activity at pH 6.0, with an activity range of pH 4.5 to 6.5. Outside this range, the enzyme's activity decreases significantly, thus reducing the ability of the lactoperoxidase system (lactooperoxidase, hydrogen peroxide, and thiocyanate / iodide) to oxidize thiocyanate or halide anions (such as iodides outside the aforementioned range).

[0230] The pH of the stomach is controlled by hydrochloric acid secreted by the gastric mucosa, which usually results in a stomach environment pH below 4.5 in various mammals, which is outside the optimal range for lactoperoxidase activity.

[0231] The lactoperoxidase system has been shown to be an effective antibacterial agent against E. coli, but this effect is only visible under specific conditions. Earnshaw et al. (Earnshaw RG, Banks JG, Francotte C, Defrise D. Inhibition of Salmonella typhimurium and E. coli (In an Infant Milk Formula by an Activated Lactoperoxidase System. J Food Prot. 1990 Feb;53(2):170-172.) demonstrated that the use of a lactoperoxidase system in the infant formula matrix leads to a prolonged lag phase in E. coli before exponential growth. Similarly, García-Graells et al. (García-Graells C, Valckx C, Michiels CW. Inactivation of Escherichia coli and Listeria innocua in milk by combined treatment with high hydrostatic pressure and the lactoperoxidase system. ApplEnviron Microbiol. 2000;66(10):4173-4179) showed that treatment with the LPO system on four different strains of E. coli produced an inhibitory effect, but no bactericidal effect was observed. Adamson and Carlsson (1982) (Lactoperoxidase and thiocyanate protect bacteria from hydrogen peroxide. Infection and Immunity. 1982, 35:1, 20-24) showed that *E. coli* is not killed by the lactoperoxidase system, but rather has an inhibitory effect under anaerobic conditions, and cells regenerate rapidly after the removal of lactoperoxidase. Therefore, the literature advises against using the lactoperoxidase system to treat *E. coli* infections, especially infections in anaerobic environments.

[0232] Furthermore, catalase is an enzyme that catalyzes the breakdown of hydrogen peroxide into water and oxygen. The role of catalase is to prevent damage from reactive oxygen species. *Escherichia coli* is a catalase-positive organism. Therefore, *E. coli* reduces hydrogen peroxide concentration through its catalase. Thus, it is not surprising that the use of lactoperoxidase systems against *E. coli* has had limited success, because the catalase produced by *E. coli* lowers the hydrogen peroxide concentration, thereby reducing the ability of thiocyanate or halide ions to be oxidized.

[0233] Earnshaw et al. (Earnshaw RG, Banks JG, Francotte C, Defrise D. Inhibition of Salmonella typhimurium and Escherichia coli in an Infant Milk Formula by an Activated Lactoperoxidase System. J Food Prot. 1990 Feb;53(2):170-172.) demonstrated that a lactoperoxidase system using a constant source of hydrogen peroxide generated from glucose / glucose oxidase has an inhibitory effect on *Escherichia coli*, while the addition of exogenous hydrogen peroxide (such as urea hydrogen peroxide adduct) outside the glucose / glucose peroxidase system results in a slight reduction in *E. coli* counts before the organism continues to grow exponentially. These results support the use of exogenous hydrogen peroxide to oxidize thiocyanate (or halide) ions in lactoperoxidase systems to produce an inhibitory effect. The observed differences in results may be due to the presence of catalase produced by *E. coli*.

[0234] Nevertheless, the inventors have found that compositions containing lactoperoxidase and iodized salt are useful in treating equine gastric ulcer syndrome. Furthermore, the compositions of the present invention containing lactoperoxidase and iodized salt do not contain hydrogen peroxide or a source of hydrogen peroxide. Suitably, the compositions further do not contain thiocyanate or a source of thiocyanate, and optionally, the compositions also do not contain other oxidizing agents, such as inorganic oxidizing agents, for example periodic acid or its salts. The compositions can be used to treat EGUS, such as EGGD and ESGD. In addition, the compositions can be used to treat wet snout disease in lambs, and diarrhea and / or scour in pigs and calves. Furthermore, the compositions are useful in treating gastrointestinal bacterial infections in mammals. The compositions of the present invention are particularly effective in treating equine squamous gastric ulcer (ESGD) and / or equine glandular gastric ulcer (EGGD), wet snout disease in lambs, Escherichia coli infection in pigs, and gastrointestinal bacterial infections in calves. The compositions of the present invention also have the potential to treat other bacterial infections in mammals, such as Escherichia coli infections in humans (especially infants) and gastric ulcers in cats, dogs, cattle (such as calves) and equines (such as horses).

[0235] In one aspect, the present invention provides a composition, such as a pharmaceutical composition, comprising: lactoperoxidase, iodized salt, and a pharmaceutically acceptable carrier and / or excipient, wherein the composition does not contain a peroxide or a peroxide source, nor does it contain a thiocyanate or a thiocyanate source.

[0236] Lactoperoxidase can be extracted from milk, and the commercial process for producing lactoperoxidase involves extracting an enzyme from milk. Lactoperoxidase is available from many food additive companies in Europe and the United States, such as Sigma-Aldrich. Suitablely, lactoperoxidase contains at least ≥200 units per mg, for example, ≥1000 units per mg. For example, each mg of lactoperoxidase may contain ≥200 units, one unit of which oxidizes 1.0 μmol of 2,2'-adiazonobis(3-ethylbenzothiazoline-6-sulfonic acid) per minute at 25°C and pH 5.5. Preferably, each mg of lactoperoxidase may contain ≥1000 units, of which 1000 units will oxidize 1.0 mmol of 2,2'-adiazonobis(3-ethylbenzothiazoline-6-sulfonic acid) within 5 minutes at pH 6.0 and 35°C.

[0237] The compositions of the present invention comprise iodized salts; for example, the compositions may comprise one or more iodized salts. Suitable iodized salts include sodium iodide, potassium iodide, lithium iodide, ammonium iodide, calcium iodide, cesium iodide, hydrogen iodide, rhodium iodide, and combinations thereof. The compositions of the present invention may comprise a single iodized salt or a combination of two or more iodized salts. For example, the compositions of the present invention may comprise a combination of two or more of sodium iodide, potassium iodide, lithium iodide, ammonium iodide, calcium iodide, cesium iodide, hydrogen iodide, and rhodium iodide.

[0238] Suitable, the weight ratio of lactoperoxidase to iodized salt is from 1:10 to 10:1. The weight ratio may vary depending on the mammal, for example, mammals of different sizes. Representative compositions for different animals within a specific size range are provided below. Furthermore, the weight ratio will vary depending on the iodized salt used. Preferably, the iodized salt is potassium iodide or sodium iodide. Here, the amount of iodized salt is also expressed in mmol.

[0239] The compositions of the present invention preferably comprise one or more carriers and / or excipients. Excipients may include, for example, fillers, diluents, binders, suspending agents, viscosity agents, coatings, flavoring agents, disintegrants, colorants, lubricants and flow aids, preservatives, and sweeteners.

[0240] Suitable excipients include one or more of magnesium stearate, lactose, glucose, microcrystalline cellulose, starch (corn), silicon dioxide, titanium dioxide, stearic acid, sodium starch glycolate, gelatin, talc, sucrose, calcium stearate, povidone, pregelatinized starch, croscarmellose, cellulose derivatives (such as hydroxypropyl methylcellulose, hydroxypropyl cellulose, or ethyl cellulose), calcium phosphate, zinc oxide, and croscarmellose. Particularly preferred examples include one or more of magnesium stearate, lactose, glucose, microcrystalline cellulose, starch (corn), silicon dioxide, titanium dioxide, stearic acid, sodium starch glycolate, gelatin, talc, sucrose, calcium stearate, and povidone.

[0241] Ideally, the composition does not contain more than 5 wt% zinc oxide based on the total weight of the composition. For example, a unit dose may contain less than 150 mg of zinc oxide. Preferably, based on the total weight of the unit dose, the unit dose contains zinc oxide in the range of about 0.01 wt% to about 5 wt%, more preferably about 0.01 wt% to about 1 wt%. For example, a unit dose may contain 1 to 10 mg of zinc oxide. Suitably, based on the total weight of the composition, a unit dose contains 0.01 wt% to about 5 wt%, preferably 0.01 wt% to 1 wt% of zinc oxide, wherein the unit dose contains 1 mg to 10 mg of zinc oxide.

[0242] Other particularly useful carriers include milk powder, colostrum (e.g., colostrum powder), whey protein, whey protein isolate, and β-lactoglobulin. Suitablely, the compositions of the present invention comprise milk powder and / or colostrum powder. Material

[0243] Lactoperoxidase is isolated from bovine milk. Lactoperoxidase activity (U / mg) is greater than 1000 units of ABTS activity (measured using UV-vis). 1000 units of ABTS activity (U): the amount of enzyme that oxidizes 1 mmol of ABTS in 5 minutes at pH 6.0 and 35°C. ABTS: 2,2'-bis(3-ethylbenzothiazoline-6-sulfonic acid).

[0244] Use commercially available iodized salt, such as potassium iodide and sodium iodide. Before preparation, sieve the salt to ensure uniform particle size.

[0245] Commercially available excipients, carriers, flavorings, sweeteners, and colorings can be used directly. Example

[0246] Equine gastric ulcer syndrome (EGUS) describes the development of ulcers in the lining of the stomach in horses. The severity of the ulcers varies, ranging from mild inflammation of the stomach wall to severe ulcers and bleeding; gastric perforation can lead to sudden death. As mentioned above, EGUS is usually treated with omeprazole (a proton pump inhibitor), which blocks the production of gastric acid. Gastric ulcers are classified according to the location of the ulcer / lesion: Equine glandular gastric ulcer (EGGD) refers to disease of the glandular portion of the stomach, and equine squamous gastric ulcer (ESGD) refers to disease of the squamous portion of the stomach. Equine gastric ulcer syndrome (EGUS) is a general term used to refer to diseases in any part of the stomach.

[0247] As mentioned above, EGUS is thought to be caused by an imbalance between mucosal invasive factors such as hydrochloric acid, pepsin, bile acids, and organic acids, and mucosal protective factors such as mucus and bicarbonate. Many factors contribute to ulcer formation, including fasting, gastric acid clearance (gastric motility and emptying), the invasiveness of gastric juices (acids, pepsin, bile acids, organic acids), and the desquamation process. Fermentation byproducts of carbohydrates may lead to the formation of volatile fatty acids, thus permanentizing hydrochloric acid-induced damage. Bacteria present in the stomach may also play a role in the occurrence and development of gastric ulcers. Lactic acid and volatile fatty acids (VFAs) are thought to play important roles in ulcer formation and progression. Lactic acid is produced by certain bacteria in the equine stomach. Lactic acid is thought to increase gastric permeability, allowing gastric acid to diffuse into the tissue layer immediately adjacent to the (deep) non-glandular mucosal stratum corneum, which in turn can lead to gastric ulcers and / or the exacerbation of existing ulcers. VFAs produced by gastric bacteria may play a similar role in reducing mucosal integrity.

[0248] Several lactic acid-producing bacteria, including Lactobacillus and Streptococcus, have been found in the equine stomach. Streptococcus bovis and Streptococcus equi are the predominant lactic acid-producing bacteria in the equine gastrointestinal tract. Other pathogenic bacteria are also present, including Clostridium perfringens and Clostridium botulinum. Other bacterial groups present in the stomach include Pseudomonas, Prevotella, Propionibacterium, Escherichia coli, Legionella, Voraxella, and Pastuerella. Despite the above, as stated in a recent review article by Vokes et al. (Animals 2023, 13, 1261. https: / / doi.org / 10.3390 / ani13071261), the relationship between bacteria and EGUS remains unclear, and the standard of care for treating EGUS is administration of omeprazole. A recent report suggests that there is no support for the use of antimicrobial agents to treat EGGD.

[0249] Furthermore, it has been reported that the combination of oral antibiotics and omeprazole for the treatment of EGUS did not improve the condition compared to omeprazole alone.

[0250] As mentioned above, the two types of gastric ulcers include squamous ulcers and glandular ulcers. Squamous ulcers occur in the upper part of the stomach, usually near the junction between the squamous and glandular tissues. Glandular ulcers occur in the lower part of the stomach when the protective mucus layer on the stomach wall ruptures.

[0251] Gastroscopy is used to diagnose and monitor stomach ulcers. This can determine the number and location of ulcers, as well as their severity.

[0252] Practitioners typically use a standard 5-point grading system to classify gastric ulcers in the glandular and squamous (non-glandular) areas of the stomach as 0 to 4.

[0253] The inventors hypothesized that lactoperoxidase and iodide sources could effectively treat EGUS. To evaluate the efficacy of the composition of this invention in treating EGUS, an animal study was conducted on five racehorses suffering from EGUS. Animals were administered 70 mg LPO and 60 mg KI tablets once daily (experimental group). The tablets also contained excipients. Control horses received no additives (control group). Endoscopic examinations were performed by a three-person team at weeks 0 (before the start of the trial), 2, 4, and 6, including a professional equine veterinarian. Horses were scored at these time points, and their clinical condition was recorded at the end of the trial.

[0254] The scores and comments on clinical conditions during the trial are summarized below:

[0255] In the experimental cohort, the ulcers of two of the three horses that completed the trial resolved, both with initial EGUS scores of 3 or higher (P3 and P4). The remaining horses that completed the trial (P2) were considered to have improved, with no ulcers in the glandular region of the stomach and only minor ulcers observed in the non-glandular (squamous) region of the stomach. The last horse in the experimental group died during the study, which was unrelated to the study itself. Similar to the other horses in the experimental group, this horse showed improvement in its EGUS score from week 0 to week 2.

[0256] The condition of the control horse did not improve after six weeks.

[0257] Advantageously, the compositions of the present invention have been shown to be effective in treating equine gastric ulcer syndrome, with improvements observed after treatment of both squamous and glandular ulcers. Unbound by conventional wisdom, it is believed that in the presence of lactoperoxidase in the equine stomach, iodides are oxidized by endogenous oxidants, which is thought to lead to the production of oxidized iodides such as hypoiodate (IO-) and hypoiodic acid (HOI). These species are potent nonspecific antimicrobial agents that may exert antimicrobial effects in the equine stomach, leading to a reduction in acids such as lactic acid and / or volatile fatty acids, and promoting ulcer healing.

[0258] Following the initial tests described above, several further tests were conducted.

[0259] EGUS Trial 2: A larger-scale study was conducted on 26 fully trained racehorses. Horses were examined the day before the start of the trial and 5 weeks after treatment. A cohort of 8 horses was also observed after 14 weeks. The trial involved the administration of daily doses of 66.4 mg LPO and 66.4 mg KI. The daily dose consisted of a solid oral dosage form containing tablets. An example tablet had the following composition:

[0260] Eight tablets were administered to each horse daily with their feed. The endoscopic results of EGUS trial 2 are shown in the table below:

[0261] The above data were used to evaluate the squamous mucosa of the test horses, i.e., the ESGD / ESGUS score. After 5 weeks, a significant reduction in ulcers was observed (approximately 49%), demonstrating the efficacy of the composition of the present invention in treating equine ulcerative gastritis syndrome. In one subgroup of 26 horses participating in the 5-week trial, administration continued for up to 14 weeks. After 14 weeks, the overall mean ESGD score decreased to 0.75. Furthermore, ulcer severity was reduced across the entire subgroup.

[0262] EGUS Trial 3: A study was conducted on 30 fully trained racehorses. The trial included 25 test horses and 5 control horses. Horses were examined one day before the start of the trial and 8 weeks after treatment. A subgroup of horses was also examined after 16 weeks. Control horses received no treatment / supplementation during the trial. The trial involved administering 83 mg LPO and 83 mg KI daily to the test horses. The daily dose consisted of a solid oral dosage form comprising tablets containing the composition of the present invention. The tablets used in the trial had the following components:

[0263] To achieve a dose of 83 mg lactoperoxidase and 83 mg potassium iodide, administer 10 tablets daily.

[0264] EGUS Trial 3 involved assessing ulcers in the squamous portion of the stomach in all horses and ulcers in the gastric gland portion in two horses (MH007 and MH010). The ESGD scores for each horse are shown in the table below:

[0265] After 8 weeks, a significant reduction in ulcers was observed, with a 46% decrease in the mean ESGD score. In the subgroup of experimental horses, ulcer reduction continued for 16 weeks. The mean ESGD score after 16 weeks was 0.8. In contrast, ulcers increased in the control group during the 8-week trial period.

[0266] The glandular ulcers in three experimental horses were also assessed:

[0267] Encouragingly, in two of the three horses with established EGGD scores, glandular ulceration was alleviated, with an observed average reduction of over 80%. This is a particularly desirable outcome given the standards of care for treating ESGD, where omeprazole has very limited efficacy in treating EGGD.

[0268] When tablets are administered together with pelleted feed, it is worth noting that the composition includes apple flavoring and sorbitol sweetener, which leads to tablets being preferred, meaning that horses prefer the taste of tablets to pelleted feed.

[0269] EGUS Trial 4: To further evaluate the efficacy of the composition of the present invention in treating EGGD, a further trial was conducted. In EGUS Trial 4, eight horses were evaluated over eight weeks. Of the eight horses involved in the trial, six were test horses, administered 83 mg LPO and 83 mg KI once daily with their feed, once daily, in 10 tablets (each tablet containing 8.3 mg LPO, 8.3 mg KI, and excipients). The tablets were similar to those used in EGUS Trial 3, although the excipient content was changed. The remaining two horses were control horses, monitored for eight weeks but receiving no treatment. ESGD and EGGD scores were measured before the start of the trial, after four weeks, and after eight weeks. The results are shown in the table below:

[0270] In the experimental horses, a 44% reduction in the average ESGD score was observed after 8 weeks. Furthermore, the EGGD score decreased by 60% over the 8-week period. In EGUS trial 4, the control horses participating in the trial did not have ulcers at the start of the trial but developed ulcers at the end. Reassuringly, the change in excipient did not alter the efficacy of the treatment.

[0271] In another trial, EGUS Trial 5, four horses were assessed with lower daily doses of LPO and KI over three weeks. Only the squamous portion of the stomach was examined. In EGUS Trial 5, the lower daily doses of 41.5 mg LPO and 41.5 mg KI showed more limited reduction in ulcers compared to the higher-dose trials.

[0272] Each of the above trials was conducted on high-performance racehorses. Treatment with at least 60 mg LPO and at least 0.36 mmol iodized salt proved highly effective, as did higher doses of at least 80 mg LPO and at least 0.48 mmol iodized salt. For smaller equines, such as horses / ponies weighing less than about 500 kg, or recreational horses with less strenuous training, lower doses of treatment, such as at least about 40 mg LPO and at least 0.24 mmol iodized salt, were considered preferred.

[0273] Advantageously, the compositions of the present invention have successfully treated EGSD and EGGD. Therefore, the compositions and methods described herein provide an alternative or additional treatment for EGUS with proton pump inhibitors such as omeprazole. Lamb wet snout disease

[0274] Wet mouth disease is a bacterial disease in newborn lambs, most commonly affecting lambs aged 6 to 48 hours. The inventors investigated the efficacy of a composition containing lactoperoxidase, iodized salt, and excipients in treating wet mouth disease in lambs. An animal study was conducted on a commercial sheep farm to determine the effects of the invention on the prevention and treatment of wet mouth disease in newborn lambs.

[0275] The experiment was conducted during two lambing periods, with one lambing cohort receiving the test material and the other serving as a control group.

[0276] Lambs in the experimental group received a composition containing 12 mg KI and 12 mg lactoperoxidase, along with excipients formulated into single tablets (400 mg tablets). The composition did not contain thiocyanate or a thiocyanate source; it did not contain peroxides or peroxide sources; nor did it contain any inorganic oxidizing agents such as periodic acid or its salts. The tablets were administered once within 2 hours of birth. Lambs in the experimental group were not given antibiotics.

[0277] The table below summarizes the mortality rate in the first 14 days after birth:

[0278] Lambs treated with the composition of the present invention during the experiment did not contract wet mouth disease. 116 lambs died in the control group, while no deaths were recorded in the experimental group.

[0279] A second experiment was conducted in which lambs were prophylactically treated with either the composition of the present invention (experimental group) or zicrolimus (Spectam ScourHalt oral solution 50 mg / ml) (control group). As described above in the first experimental group, the composition of the present invention was administered as a single tablet. The composition comprises 10 mg KI, 12 mg lactoperoxidase, and excipients, and is formulated into a tablet. As mentioned above, the tablet is free of thiocyanate or thiocyanate sources, and also free of peroxides or peroxide sources. The tablet also does not contain inorganic oxidizing agents such as periodic acid or its salts.

[0280] The second trial was conducted in an indoor lowland ewe lambing flock in Scotland. The prevalence of wet mouth disease in lambs born over the past four years ranged from 2% to 5.5%, which is typical for similar flocks. Standard management involved administering a 1 mL dose of Spectam Scour Halt oral solution containing 50 mg / mL zirconia (calculated as zirconia dihydrochloride pentahydrate) as soon as possible after birth, within 48 hours. Ewes and lambs were kept in separate pens for 24 to 48 hours, then moved to a communal pen until the weather was mild enough for grazing.

[0281] Over a four-week period, 434 lambs were born in an indoor system. Three shepherds worked in shifts of eight hours each, with one shepherd administering the test composition in tablet form (i.e., the composition of the invention in tablet form), and the other two shepherds administering a single dose of 50 mg / ml Spectam Scour Halt oral solution to the control group. 282 lambs received a single dose of Spectam Scour Halt oral solution, and 152 lambs received a single dose of the test composition in tablet form. The incidence of wet mouth disease was approximately 2.5% (7 lambs) in the control group and approximately 2% (3 lambs) in the test group. Therefore, in the event of wet mouth disease, the efficacy of the composition of the invention is at least comparable to (if not slightly better than) prophylactic antibiotic treatment.

[0282] Advantageously, the compositions of the present invention effectively treat and / or prevent wet mouth disease in lambs. Without being bound by theory, it is believed that iodized salts are oxidized by endogenous oxidants in the lamb's gastrointestinal tract in the presence of lactoperoxidase, which is thought to lead to the production of oxidized iodides, such as hypoiodide (IO3). -The compositions contain thiocyanate and hypoiodic acid (HOI). These substances are potent, nonspecific antimicrobial agents and are believed to kill bacteria associated with wet mouth disease in newborn lambs. Advantageously, the compositions of the present invention do not contain thiocyanate or thiocyanate sources, nor do they contain peroxides or peroxide sources. They also further do not contain strong oxidizing agents, such as inorganic oxidizing agents, periodic acid, or salts thereof. Compared to conventional lactoperoxidase systems, especially in liquid formulations, the absence of such reactive substances advantageously and significantly extends the shelf life of the compositions of the present invention. pig research

[0283] Bacterial infections in pigs can cause diarrhea or scour. For example, infection with E. coli can lead to E. coli disease, which in turn causes diarrhea or scour. Post-weaning diarrhea (PWD) in pigs is often associated with enterotoxigenic E. coli (ETEC), one of the most common swine diseases, causing significant economic losses worldwide.

[0284] A study was conducted to determine the potential effects of the compositions of the present invention on controlling Escherichia coli infection and improving animal health.

[0285] Piglets were weaned at 28 days of age, with an average weight of 8.6 ± 0.98 kg. At weaning (i.e., no longer suckling), piglets in the litter were evenly divided into groups of up to 14: a control group (without additional feed ingredients), a first experimental group treated with the composition of this invention, and a second experimental group treated with zinc oxide. After the experiment, the pigs were fed the starting feed until day 14 of the experiment.

[0286] Body weight and feed intake were recorded on days 0, 7 and 14 of the experiment.

[0287] The composition of this invention comprises 10 mg LPO and 8 mg KI, and excipients. The composition is formulated as a powder. The composition is administered once daily with feed for 14 days. The powder composition is free of thiocyanate or thiocyanate sources, peroxides or peroxide sources, and inorganic oxidants such as periodic acid or its salts. Zinc oxide was applied to a second experimental group at a concentration of 3000 ppm (i.e., 3 g / kg feed).

[0288] Average daily weight gain (g / d) and average daily feed intake on day 14

[0289] The daily weight gain of pigs receiving the experimental material increased, and the weight gain of pigs receiving the experimental material was significantly higher than that of the control group.

[0290] Average weight (kg)

[0291] Compared to the control group, the pigs that received the experimental material gained weight. The pigs could be fed freely.

[0292] Further studies were conducted on 240 pigs using higher doses of lactoperoxidase and potassium iodide. Pigs were weighed and assigned to the experiment at weaning (approximately 28 days old). The pigs were divided into three groups: (i) Positive control (PC) group – fed a standard seedling diet containing 3100 ppm ZnO (ii) Negative control (NC) group – fed standard seedling diet (<150ppm ZnO) (iii) Experimental group – fed a standard seedling diet (<150ppm ZnO) plus the composition of the present invention – a single daily dose containing 20mg LPO and 20mg KI. The groups were evenly divided according to total weight and sex characteristics, with each group consisting of 5 pigs per pen. As mentioned above, diets (ii) and (iii) did not contain therapeutic amounts of ZnO. Pigs were weighed on days 7 and 14 of the study. The general health of the pigs was assessed each morning, and feces were examined for scour / diarrhea, with each pig assigned a cleanliness score. All treatments had similar weaning weights, starting at approximately 7.7 kg. At the end of 14 days, pigs fed the PC diet weighed the heaviest, while those fed the NC diet lost approximately 0.8 kg. Pigs fed the experimental diet (group (iii) above) had moderate weights, but after 7 days, their weights were roughly the same as those on the PC diet. The mean health scores were similar across groups, but the experimental groups had the highest cleanliness scores, while the positive control group had the lowest.

[0293] In both of the aforementioned trials, although the groups treated with zinc oxide (at concentrations of 3000 ppm (trial 1) or 3100 ppm (trial 2)) showed the greatest weight gain, the compositions of the present invention also resulted in weight gain compared to the negative control group. Furthermore, once the zinc oxide products available on the market for such treatments are exhausted before July 2022, Europe will prohibit the use of high concentrations of zinc oxide (e.g., 1000 ppm or higher) as feed additives for pigs. Therefore, suitable alternative feed additives and / or preventative treatments are needed to combat porcine colibacillosis, scour, and diarrhea. The compositions of the present invention have proven to be suitable alternatives to zinc oxide for preventing scour in pigs. Advantageously, the compositions of the present invention are effective in treating and / or preventing scour or diarrhea in pigs, particularly in newly weaned piglets (e.g., 28-day-old pigs). Unbound by theory, it is believed that in the presence of lactoperoxidase, iodized salt is oxidized by endogenous oxidants in the pig's gastrointestinal tract, which is thought to lead to the production of oxidized iodides, such as hypoiodide (IO3). - And hypoiodic acid (HOI). These species are potent nonspecific antibacterial agents and are believed to kill bacteria that cause diarrhea or scour in pigs. Advantageously, the compositions of the present invention do not contain thiocyanate or thiocyanate sources, nor do they contain peroxides or peroxide sources. They also do not contain strong oxidizing agents, such as inorganic oxidizing agents, periodic acid, or salts thereof. The absence of such reactive substances advantageously and significantly extends the shelf life of the compositions of the present invention compared to conventional lactoperoxidase systems.

[0294] Furthermore, the compositions of the present invention can effectively control Escherichia coli infection in pigs, for example, and can be used for prevention. For example, the compositions of the present invention can be used to prevent swine diarrhea or scour, such as diarrhea or scour caused by Escherichia coli infection.

[0295] In all the foregoing aspects, the compositions of the present invention comprise lactoperoxidase and iodized salt. The compositions of the present invention have been shown to be effective in treating and / or preventing various diseases in different species. Representative doses for treating different species are as follows:

[0296] Example 1: Horse (approximately 500 kg in weight): The daily dose contains 50-85 mg of potassium iodide and 50-85 mg of lactoperoxidase, for example, 60-80 mg of potassium iodide and 60-80 mg of lactoperoxidase.

[0297] Preferred dosage form: solid dosage form, such as tablets.

[0298] Example 2: Newborn lambs (weighing approximately 5.5 kg): Treat WMD with a unit dose containing 8-20 mg potassium iodide and 8-20 mg lactoperoxidase, for example, a unit dose containing 10 mg potassium iodide and 12 mg lactoperoxidase (e.g., administered daily).

[0299] Preferred dosage form: tablets or oral suspension

[0300] Prophylactic treatment can be administered to lambs as soon as possible after birth, for example, by administering tablets or oral suspensions containing lactoperoxidase and potassium iodide. This is typically within 48 hours of birth, preferably within 24 hours, more preferably within 12 hours, such as within 6 hours or 2 hours after birth.

[0301] Example 3: Weaned piglets (weighing approximately 5-7 kg): Treat / prevent diarrhea / scour with a unit dose containing, for example, 8-30 mg potassium iodide and 8-30 mg lactoperoxidase, or a unit dose containing, for example, 20 mg potassium iodide and 20 mg lactoperoxidase (e.g., administered daily).

[0302] Preferred dosage forms: soluble powder, effervescent tablets, or liquid formulations.

[0303] Example 4: Dogs / cats (approximately 2-50 kg in weight): Unit doses include, for example, 2-4 mg potassium iodide and 2-4 mg lactoperoxidase per kg of body weight, such as 2.5 mg potassium iodide and 3 mg lactoperoxidase per kg of body weight.

[0304] Preferred dosage forms: soluble powder, effervescent tablets, or liquid formulations.

[0305] For example, the above dosage can be added to animal feed or applied directly as appropriate.

[0306] Example 5: Human infants (weighing approximately 2-25 kg): Unit doses include, for example, 3-10 mg potassium iodide and 3-10 mg lactoperoxidase, such as 5 mg potassium iodide and 7.5 mg lactoperoxidase.

[0307] Preferred dosage form: liquid formulation or suspension.

[0308] For example, the dosage can be applied once or twice a day for two to three consecutive days.

[0309] The compositions of the present invention may contain a carrier or an excipient.

[0310] When referring to this invention, the terms “comprise” and “comprising” as used herein are used to specify the presence of the said feature, integer, step or component, but do not exclude the presence or addition of one or more other features, integrals, steps, components or groups thereof.

[0311] It should be understood that, for clarity, certain features of the invention described in the context of individual embodiments may also be provided in combination in a single embodiment. Conversely, for brevity, various features of the invention described in the context of individual embodiments may also be provided individually or in any suitable sub-combination. Implementation Plan

[0312] 1. A composition, such as a pharmaceutical composition, comprising: Lactoperoxidase, iodized salt, and Pharmaceutically acceptable carriers and / or excipients For the treatment or prevention of equine gastric ulcer syndrome, optionally including equine squamous gastric ulcer and / or equine glandular gastric ulcer.

[0313] 2. The composition for use according to embodiment 1, wherein the composition does not contain peroxide or a peroxide source.

[0314] 3. The composition for use according to embodiment 1 or 2, wherein the composition does not contain thiocyanate or a thiocyanate source.

[0315] 4. The composition for use according to any of the foregoing embodiments, wherein the weight ratio of lactoperoxidase to iodized salt is 1:10 to 10:1, preferably 1:3 to 3:1, most preferably 1:1.3 to 1.3:1, for example about 1:1.

[0316] 5. The composition for use according to any of the foregoing embodiments, wherein the iodized salt is selected from sodium iodide, potassium iodide, lithium iodide, ammonium iodide, calcium iodide, cesium iodide, hydrogen iodide, rhodium iodide, and combinations thereof, preferably sodium iodide and / or potassium iodide, more preferably potassium iodide.

[0317] 6. The composition for use according to any of the foregoing embodiments, wherein the composition is a solid dosage form, such as a tablet or powder dosage form.

[0318] 7. A composition for use according to any one of embodiments 1 to 5, wherein the composition is a liquid dosage form, such as a suspension.

[0319] 8. The composition for use according to any of the foregoing embodiments further comprises vitamin C.

[0320] 9. The composition for use according to any of the foregoing embodiments further comprises one or more of magnesium stearate, lactose, glucose, microcrystalline cellulose, starch (corn), silicon dioxide, titanium dioxide, colostrum, zinc oxide, hydroxypropyl methylcellulose, stearic acid, sodium starch glycolate, gelatin, talc, sucrose, calcium stearate, and povidone.

[0321] 10. The composition for use according to any of the foregoing embodiments, wherein the treatment comprises daily administration of at least 0.24 mmol of iodized salt and at least 40 mg of lactoperoxidase, preferably, wherein the treatment comprises daily administration of at least 0.36 mmol of iodized salt and at least 60 mg of lactoperoxidase, more preferably, wherein the treatment comprises daily administration of at least 0.48 mmol of iodized salt and at least 80 mg of lactoperoxidase.

[0322] 11. The composition for use according to any of the foregoing embodiments, wherein the treatment comprises administering 0.24 mmol to 1.2 mmol of iodized salt and 40 mg to 200 mg of lactoperoxidase daily to an equine animal, for example, administering 0.36 mmol to 1.2 mmol of iodized salt and 60 mg to 200 mg of lactoperoxidase daily to an equine animal, optionally administering 0.48 mmol to 0.60 mmol of iodized salt and 80 mg to 100 mg of lactoperoxidase daily to an equine animal.

[0323] 12. The composition for use according to any of the foregoing embodiments, wherein the treatment comprises administering at least 40 mg of iodized salt and at least 40 mg of lactoperoxidase daily, preferably, the treatment comprises administering at least 60 mg of iodized salt and at least 50 mg of lactoperoxidase daily. For example, the treatment comprises administering at least 60 mg of iodized salt and at least 60 mg of lactoperoxidase daily, more preferably, wherein the treatment comprises administering at least 80 mg of iodized salt and at least 80 mg of lactoperoxidase daily.

[0324] 13. The composition for use according to any of the foregoing embodiments, wherein the treatment comprises administering 40 mg to 200 mg of iodized salt and 40 mg to 200 mg of lactoperoxidase daily to an equine, for example, administering 60 mg to 200 mg of iodized salt and 60 mg to 200 mg of lactoperoxidase daily to an equine, optionally administering 80 mg to 100 mg of iodized salt and 80 mg to 100 mg of lactoperoxidase daily to an equine.

[0325] 14. The composition for use according to any of the foregoing embodiments, wherein the treatment lasts for at least four weeks, preferably at least eight weeks, more preferably at least 12 weeks.

[0326] 15. The composition for use according to any of the foregoing embodiments, wherein the treatment comprises applying the composition daily for at least four days a week, preferably at least five days a week.

[0327] 16. A composition for use according to any of the foregoing embodiments, wherein a unit dose of the composition comprises lactoperoxidase in an amount of 0.5 mg to 200 mg, for example 1 mg to 100 mg, preferably 5 mg to 50 mg, more preferably 8 mg to 20 mg, for example 8 mg to 12 mg.

[0328] 17. The composition for use according to any of the foregoing embodiments, wherein a unit dose of the composition comprises iodized salt in an amount of 0.003 mmol to 1.2 mmol, for example 0.006 mmol to 0.6 mmol, preferably 0.030 mmol to 0.30 mmol, more preferably 0.048 mmol to 0.12 mmol, for example 0.048 mmol to 0.072 mmol.

[0329] 18. A composition for use according to any of the foregoing embodiments, wherein a unit dose of the composition comprises iodized salt in a content of 0.5 mg to 200 mg, for example 1 mg to 100 mg, preferably 5 mg to 50 mg, more preferably 8 mg to 20 mg, for example 8 mg to 12 mg.

[0330] 19. A composition for use according to any of the foregoing embodiments, wherein a unit dose of the composition comprises lactoperoxidase in an amount of about 0.5 wt% to about 15 wt% based on the total weight of the unit dose, preferably about 0.5 wt% to about 5 wt%, more preferably about 1 wt% to about 2 wt%, for example about 1 wt% to 1.5 wt%.

[0331] 20. A composition for use according to any of the foregoing embodiments, wherein a unit dose of the composition comprises iodized salt in an amount of about 0.5 wt% to about 15 wt% based on the total weight of the unit dose, preferably about 0.5 wt% to about 5 wt%, more preferably about 1 wt% to about 2 wt%, for example about 1 wt% to 1.5 wt%.

[0332] 21. The composition for use according to any of the foregoing embodiments, wherein a unit dose of the composition comprises 5 mg to 50 mg of lactoperoxidase, preferably 8 mg to 20 mg of lactoperoxidase, and wherein a unit dose of the composition comprises 0.030 mmol to 0.30 mmol of iodized salt, preferably 0.048 mmol to 0.12 mmol of iodized salt.

[0333] 22. The composition for use according to any of the foregoing embodiments, wherein the content of lactoperoxidase is from about 0.5 wt% to about 5 wt% based on the total weight of the unit dose, preferably from about 1 wt% to about 2 wt% based on the total weight of the unit dose, and wherein the content of iodized salt is from about 0.5 wt% to about 5 wt% based on the total weight of the unit dose, preferably from about 1 wt% to about 2 wt% based on the total weight of the unit dose.

[0334] 23. A composition for use according to any of the foregoing embodiments, wherein a unit dose of the composition comprises lactoperoxidase in a content of about 8 mg to about 20 mg and in a content of about 0.5 wt% to about 5 wt% based on the total weight of the unit dose, and wherein the iodized salt is potassium iodide in a content of about 8 mg to 20 mg and in a content of about 0.5 wt% to about 5 wt% based on the total weight of the unit dose, and wherein the composition optionally comprises vitamin C and optionally comprises zinc oxide.

[0335] 24. A combination for treating equine gastric ulcer syndromes such as equine squamous gastric ulcer and / or equine glandular gastric ulcer, said combination comprising: lactoperoxidase; and Iodized salt; The lactoperoxidase and iodized salt are applied sequentially or simultaneously to equines, such as horses or ponies, in a relative weight ratio of 1:10 to 10:1, preferably in a relative weight ratio of about 1:2 to 2:1, and more preferably in a relative weight ratio of about 1:1.3 to 1.3:1.

[0336] 25. The combination of uses according to embodiment 24, wherein the treatment does not contain peroxide or a peroxide source.

[0337] 26. A combination of uses according to embodiments 24 or 25, wherein the treatment does not include the application of thiocyanate or a thiocyanate source.

[0338] 27. A combination of uses according to any one of embodiments 24 to 26, wherein the iodized salt is selected from sodium iodide, potassium iodide, lithium iodide, ammonium iodide, calcium iodide, cesium iodide, hydrogen iodide, rhodium iodide, and combinations thereof, preferably sodium iodide and / or potassium iodide, more preferably potassium iodide.

[0339] 28. A combination of uses according to any one of embodiments 24 to 27, wherein the treatment involves the administration of one or more oral dosage forms.

[0340] 29. The combination of uses according to embodiment 28, wherein the oral dosage form is a solid dosage form, such as a tablet or powder, or a liquid dosage form or suspension.

[0341] 30. The combination of uses according to any of the foregoing embodiments further comprises vitamin C.

[0342] 31. A combination of uses according to any one of embodiments 24 to 30, wherein the combination comprises an oral dosage form comprising one or more of magnesium stearate, lactose, glucose, microcrystalline cellulose, starch (corn), silicon dioxide, titanium dioxide, zinc oxide, colostrum, hydroxypropyl methylcellulose, stearic acid, sodium starch glycolate, gelatin, talc, sucrose, calcium stearate, and povidone, preferably wherein the oral dosage form comprises magnesium stearate, microcrystalline cellulose, zinc oxide, and colostrum.

[0343] 32. A combination of uses according to any one of embodiments 24 to 31, wherein the combination includes an oral dosage form comprising one or more flavoring agents, sweeteners and / or colorings.

[0344] 33. A combination of uses according to any one of embodiments 24 to 32, wherein the treatment comprises daily administration of at least 0.24 mmol of iodized salt and at least 40 mg of lactoperoxidase, preferably, the treatment comprises daily administration of at least 0.36 mmol of iodized salt and at least 60 mg of lactoperoxidase, more preferably, the treatment comprises daily administration of at least 0.48 mmol of iodized salt and at least 80 mg of lactoperoxidase.

[0345] 34. A combination of uses according to any one of embodiments 24 to 33, wherein the treatment comprises administering 40 mg to 200 mg of iodized salt and 40 mg to 200 mg of lactoperoxidase daily to an equine, for example, administering 60 mg to 200 mg of iodized salt and 60 mg to 200 mg of lactoperoxidase daily to an equine, optionally administering 80 mg to 100 mg of iodized salt and 80 mg to 100 mg of lactoperoxidase daily to an equine.

[0346] 35. A combination of uses according to any one of embodiments 24 to 34, wherein the treatment comprises administering at least 40 mg of iodized salt and at least 40 mg of lactoperoxidase daily, preferably, the treatment comprises administering at least 60 mg of iodized salt and at least 50 mg of lactoperoxidase daily, for example, the treatment comprises administering at least 60 mg of iodized salt and at least 60 mg of lactoperoxidase daily, more preferably, the treatment comprises administering at least 80 mg of iodized salt and at least 80 mg of lactoperoxidase daily.

[0347] 36. A combination of uses according to any one of embodiments 24 to 35, wherein the treatment comprises administering 40 mg to 200 mg of iodized salt and 40 mg to 200 mg of lactoperoxidase daily to an equine, for example, administering 60 mg to 200 mg of iodized salt and 60 mg to 200 mg of lactoperoxidase daily to an equine, optionally administering 80 mg to 100 mg of iodized salt and 80 mg to 100 mg of lactoperoxidase daily to an equine.

[0348] 37. A feed additive composition or feed supplement composition comprising: lactoperoxidase, and Iodized salt The composition therein does not contain peroxide or peroxide source; and The composition does not contain thiocyanate or a thiocyanate source; The lactoperoxidase content is at least 40 mg, and the iodized salt content is at least 0.24 mmol. Optionally, the weight ratio of lactoperoxidase to iodized salt is in the range of 1:1.3 to 1.3:1; Optionally, the iodized salt is selected from sodium iodide, potassium iodide, lithium iodide, ammonium iodide, calcium iodide, cesium iodide, hydrogen iodide, rhodium iodide, and combinations thereof, preferably sodium iodide and / or potassium iodide, more preferably potassium iodide; and Optionally, the composition is a tablet, powder, liquid, or oral suspension.

[0349] 38. The feed additive composition or feed supplement composition according to embodiment 37, comprising at least 0.36 mmol of iodized salt and at least 60 mg of lactoperoxidase, preferably at least 0.48 mmol of iodized salt and at least 80 mg of lactoperoxidase.

[0350] 39. The feed additive composition or feed supplement composition according to embodiment 37 or 38, comprising 0.24 mmol to 1.2 mmol of iodized salt, preferably 0.24 mmol to 0.6 mmol of iodized salt, optionally, the feed additive comprises 0.36 mmol to 1.2 mmol of iodized salt, for example 0.36 mmol to 0.6 mmol of iodized salt, most preferably 0.24 mmol to 0.51 mmol of iodized salt.

[0351] 40. The feed additive composition or feed supplement composition according to any one of embodiments 37 to 39, wherein the iodized salt is potassium iodide, and the composition contains 40 to 200 mg of potassium iodide, preferably 40 to 120 mg of potassium iodide, optionally 40 to 100 mg of potassium iodide, and most preferably 40 to 85 mg of potassium iodide.

[0352] 41. The feed additive composition or feed supplement composition according to any one of embodiments 37 to 40, wherein the composition is formulated as a unit dosage form, wherein the unit dose contains 5 to 20 mg of lactoperoxidase, preferably 8 to 15 mg of lactoperoxidase.

[0353] 42. The feed additive composition or feed supplement composition according to any one of embodiments 37 to 41, wherein the composition is formulated in a unit dosage form, wherein the content of lactoperoxidase is from about 0.5 wt% to about 15 wt% based on the total weight of the unit dose, preferably from about 0.5 wt% to about 5 wt%, more preferably from about 1 wt% to about 2 wt%, for example from about 1 wt% to 1.5 wt%.

[0354] 43. The feed additive composition or feed supplement composition according to any one of embodiments 37 to 42, wherein the composition is formulated in a unit dosage form comprising 0.03 mmol to 0.12 mmol of iodized salt, preferably 0.048 mmol to 0.09 mmol of iodized salt, more preferably 0.048 mmol to 0.072 mmol of iodized salt.

[0355] 44. The feed additive composition or feed supplement composition according to any one of embodiments 37 to 43, wherein the composition is formulated as a unit dosage form comprising, for example, iodized salt in an amount of about 0.5 wt% to about 15 wt% based on the total weight of the unit dose, preferably about 0.5 wt% to about 5 wt%, more preferably about 1 wt% to about 2 wt%.

[0356] 45. A feed additive composition or feed supplement composition according to any one of embodiments 37 to 44, wherein the composition is formulated as a unit dosage form comprising 5 to 20 mg of lactoperoxidase and 0.03 mmol to 0.12 mmol of iodized salt, wherein the content of lactoperoxidase is from about 0.5 wt% to about 5 wt% based on the total weight of the unit dose, and wherein the content of iodized salt is from about 0.5% to about 5% based on the total weight of the unit dose.

[0357] 46. ​​A method for treating and / or preventing equine gastric ulcer syndrome, comprising administering to equines in need a composition comprising lactoperoxidase, iodized salt and a pharmaceutically acceptable carrier and / or excipient, thereby treating or preventing equine gastric ulcer syndrome.

[0358] 47. The method according to embodiment 46, wherein equine gastric ulcer syndrome includes equine squamous gastric ulcer and / or equine glandular gastric ulcer.

[0359] 48. The method according to embodiment 46 or 47, wherein the weight ratio of lactoperoxidase to iodized salt is 1:10 to 10:1, preferably 1:3 to 3:1, most preferably 1:1.3 to 1.3:1, for example about 1:1.

[0360] 49. The method according to any one of embodiments 46 to 48, wherein the iodized salt is selected from sodium iodide, potassium iodide, lithium iodide, ammonium iodide, calcium iodide, cesium iodide, hydrogen iodide, rhodium iodide, or combinations thereof.

[0361] 50. The method according to any one of embodiments 46 to 49, wherein the iodized salt is sodium iodide and / or potassium iodide, more preferably potassium iodide.

[0362] 51. The method according to any one of embodiments 46 to 50, wherein the method comprises administering 0.24 mmol to 1.2 mmol of iodized salt and 40 mg to 200 mg of lactoperoxidase to an equine animal daily.

[0363] 52. The method according to any one of embodiments 46 to 51, wherein the method comprises administering 0.36 mmol to 1.2 mmol of iodized salt and 60 mg to 200 mg of lactoperoxidase to an equine animal daily.

[0364] 53. The method according to any one of embodiments 46 to 52, wherein the method comprises administering 0.48 mmol to 0.60 mmol of iodized salt and 80 mg to 100 mg of lactoperoxidase to an equine animal daily.

[0365] 54. The method according to any one of embodiments 46 to 53, wherein the method comprises administering 40 mg to 200 mg of iodized salt and 40 mg to 200 mg of lactoperoxidase to an equine animal daily.

[0366] 55. The method according to any one of embodiments 46 to 54, wherein the method comprises administering 60 mg to 200 mg of iodized salt and 60 mg to 200 mg of lactoperoxidase to an equine animal daily.

[0367] 56. The method according to any one of embodiments 46 to 55, wherein the method comprises administering 80 mg to 100 mg of iodized salt and 80 mg to 100 mg of lactoperoxidase to an equine animal daily.

[0368] 57. The method according to any one of embodiments 46 to 56, wherein the method includes administering one or more oral dosage forms.

[0369] 58. The method according to any one of embodiments 46 to 57, wherein the method comprises administering one or more unit doses of the composition.

[0370] 59. The method according to any one of embodiments 58, wherein a unit dose of the composition comprises 5 mg to 50 mg of lactoperoxidase, and wherein a unit dose of the preparation comprises 0.030 mmol to 0.30 mmol of iodized salt.

[0371] 60. The method according to any one of embodiments 58 or 59, wherein a unit dose of said composition comprises 8 mg to 20 mg of lactoperoxidase, and wherein a unit dose of said composition comprises 0.048 mmol to 0.12 mmol of iodized salt.

[0372] 61. The method according to any one of embodiments 58 to 60, wherein a unit dose of the composition comprises lactoperoxidase in a content of about 8 mg to about 20 mg and in a content of about 0.5 wt% to about 5 wt% based on the total weight of the unit dose, and wherein the iodized salt is potassium iodide in a content of about 8 mg to 20 mg and in a content of about 0.5 wt% to about 5 wt% based on the total weight of the unit dose.

[0373] 62. The method according to any one of embodiments 46 to 61, wherein the composition comprises vitamin C and / or zinc oxide.

[0374] 63. The method according to any one of Examples 46 to 62, wherein the equine is a horse or a foal.

[0375] 64. A method for treating and / or preventing equine gastric ulcer syndrome, comprising administering a combination to an equine animal in need, said combination comprising: lactoperoxidase; and Iodized salt; The lactoperoxidase and iodized salt are administered sequentially or simultaneously to equines to treat or prevent equine gastric ulcer syndrome.

[0376] 65. The method according to embodiment 64, wherein lactoperoxidase and iodized salt are applied in a relative weight ratio of about 1:2 to 2:1, more preferably in a relative weight ratio of about 1:1.3 to 1.3:1.

[0377] 66. The method according to embodiment 64 or 65 includes administering 0.36 mmol to 1.2 mmol of iodized salt and 60 mg to 200 mg of lactoperoxidase to equines daily.

[0378] 67. The method according to any one of embodiments 64 to 44, wherein the equine gastric ulcer syndrome is equine squamous gastric ulcer or equine glandular gastric ulcer.

[0379] 68. The method according to any one of embodiments 64 to 67, wherein the equine gastric ulcer syndrome is equine glandular gastric ulcer.

[0380] 69. A method for treating equine gastric ulcer syndrome, comprising administering to horses in need a composition comprising lactoperoxidase, iodized salt, and a pharmaceutically acceptable carrier and / or excipient, wherein the iodized salt comprises potassium iodide, and wherein the weight ratio of lactoperoxidase to potassium iodide is 1:3 to 3:1. The composition is formulated as a solid oral dosage form. The composition does not contain peroxide or peroxide source. The composition described herein does not contain thiocyanate or a thiocyanate source. The method described involves administering 0.36 mmol to 0.6 mmol of iodized salt and 60 mg to 100 mg of lactoperoxidase to horses daily to treat equine gastric ulcer syndrome.

[0381] 70. The method according to embodiment 69, comprising administering one or more unit doses of a solid oral dosage form, wherein the unit dose of the solid dosage form comprises: lactoperoxidase in a content of about 8 mg to about 20 mg and in a content of about 0.5 wt% to about 5 wt% based on the total weight of the unit dose, and wherein the iodized salt is potassium iodide in a content of about 8 mg to 20 mg and in a content of about 0.5 wt% to about 5 wt% based on the total weight of the unit dose.

[0382] 71. The method according to embodiment 69 or 70, wherein the composition comprises vitamin C and zinc oxide.

[0383] 72. The method according to any one of embodiments 69 to 71, wherein the weight ratio of lactoperoxidase to potassium iodide is 1:1.3 to 1.3:1.

[0384] 73. The method according to any one of embodiments 69 to 72, wherein the method comprises administering 0.48 mmol to 0.6 mmol of iodized salt and 80 mg to 100 mg of lactoperoxidase to the horse daily.

[0385] 74. The method according to any one of embodiments 69 to 73, wherein the equine gastric ulcer syndrome is equine squamous gastric ulcer or equine glandular gastric ulcer.

[0386] 75. The method according to any one of embodiments 69 to 74, wherein the equine gastric ulcer syndrome is equine glandular gastric ulcer.

Claims

1. A composition, such as a pharmaceutical composition, comprising: Lactoperoxidase, iodized salt, and Pharmaceutically acceptable carriers and / or excipients For the treatment or prevention of equine gastric ulcer syndrome, optionally wherein the equine gastric ulcer syndrome includes equine squamous gastric ulcer and / or equine glandular gastric ulcer.

2. The composition for use according to claim 1, wherein the weight ratio of lactoperoxidase to iodized salt is 1:10 to 10:1, preferably 1:3 to 3:1, most preferably 1:1.3 to 1.3:1, for example about 1:

1.

3. The composition for use according to any one of the preceding claims, wherein the iodized salt is selected from sodium iodide, potassium iodide, lithium iodide, ammonium iodide, calcium iodide, cesium iodide, hydrogen iodide, rhodium iodide, and combinations thereof, preferably sodium iodide and / or potassium iodide, more preferably potassium iodide.

4. The composition for use according to any one of the preceding claims, wherein the treatment comprises daily administration of at least 0.24 mmol of iodized salt and at least 40 mg of lactoperoxidase, preferably, wherein the treatment comprises daily administration of at least 0.36 mmol of iodized salt and at least 60 mg of lactoperoxidase, more preferably, wherein the treatment comprises daily administration of at least 0.48 mmol of iodized salt and at least 80 mg of lactoperoxidase.

5. The composition for use according to any one of the preceding claims, wherein the treatment comprises administering 0.24 mmol to 1.2 mmol of iodized salt and 40 mg to 200 mg of lactoperoxidase to an equine animal daily.

6. The composition for use according to any one of the preceding claims, wherein the treatment comprises administering 0.36 mmol to 1.2 mmol of iodized salt and 60 mg to 200 mg of lactoperoxidase to an equine animal daily.

7. The composition for use according to any one of the preceding claims, wherein the treatment comprises daily administration of 0.48 mmol to 0.60 mmol of iodized salt and 80 to 100 mg of lactoperoxidase.

8. The composition for use according to any one of the preceding claims, wherein the treatment comprises administering at least 40 mg of the iodized salt and at least 40 mg of the lactoperoxidase daily, preferably, wherein the treatment comprises administering at least 60 mg of the iodized salt and at least 60 mg of the lactoperoxidase daily, more preferably, wherein the treatment comprises administering at least 80 mg of the iodized salt and at least 80 mg of the lactoperoxidase daily.

9. A composition for use according to any one of the preceding claims, wherein the composition is formulated as one or more oral dosage forms.

10. The composition for use according to any one of the preceding claims, wherein the treatment comprises administering one or more unit doses of the composition.

11. The composition for use according to claim 10, wherein a unit dose of the composition comprises 5 mg to 50 mg of lactoperoxidase, and wherein a unit dose of the composition comprises 0.030 mmol to 0.30 mmol of iodized salt.

12. The composition for use according to claim 11, wherein a unit dose of the composition comprises 8 mg to 20 mg of lactoperoxidase, and wherein a unit dose of the composition comprises 0.048 mmol to 0.12 mmol of iodized salt.

13. A composition for use according to any one of the preceding claims, wherein a unit dose of the composition comprises lactoperoxidase in an amount of about 8 mg to about 20 mg and in an amount of about 0.5 wt% to about 5 wt% based on the total weight of the unit dose, and wherein the iodized salt is potassium iodide in an amount of about 8 mg to 20 mg and in an amount of about 0.5 wt% to 5 wt% based on the total weight of the unit dose.

14. A composition for use according to any one of the preceding claims, wherein the composition further comprises vitamin C and optionally zinc oxide.

15. The composition for use according to any one of the preceding claims, wherein the equine is a horse or a pony.

16. A combination for treating equine gastric ulcer syndromes such as equine squamous gastric ulcer and / or equine glandular gastric ulcer, said combination comprising: lactoperoxidase; and Iodized salt; The lactoperoxidase and iodized salt are optionally applied sequentially or simultaneously to equines, such as horses or ponies, in a relative weight ratio of 1:10 to 10:1, preferably in a relative weight ratio of about 1:2 to 2:1, and more preferably in a relative weight ratio of about 1:1.3 to 1.3:

1.

17. The combination of uses according to claim 16, wherein the treatment comprises administering to the equine at least 0.24 mmol of iodized salt and at least 40 mg of lactoperoxidase daily, preferably, the treatment comprises administering to the equine at least 0.36 mmol of iodized salt and at least 60 mg of lactoperoxidase daily, more preferably, administering to the equine at least 0.48 mmol of iodized salt and at least 80 mg of lactoperoxidase daily.

18. The combination of uses according to claim 16 or 17, wherein the treatment comprises administering 0.24 mmol to 1.2 mmol of iodized salt and 40 mg to 200 mg of lactoperoxidase to the equine daily.

19. The combination of uses according to claim 16 or 17, wherein the treatment comprises administering 0.36 mmol to 1.2 mmol of iodized salt and 60 mg to 200 mg of lactoperoxidase to the equine daily.

20. The combination of uses according to any one of claims 16 to 19, wherein the equine gastric ulcer syndrome is equine squamous gastric ulcer.

21. The combination of uses according to any one of claims 16 to 19, wherein the equine gastric ulcer disease is equine glandular gastric ulcer.

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