Therapeutic clay compositions and methods of use

Abstract

The present invention provides a method for improving the efficiency, growth and performance of animals by orally administering to the animals an effective amount of a therapeutic clay. The method can reduce embryonic loss, increase litter size, increase live births, improve the immune status of the maternal animal, reduce the concentration of maternal fecal amino acids, reduce the concentration of maternal fecal short-chain amino acids, increase the birth litter weight of the maternal animal, increase the colostrum intake of young animals, reduce the pre-weaning mortality of young animals, reduce the number of young animals lost due to low vitality, reduce the number of young animals weaned, improve the immune status of young animals at weaning, reduce the number of young animals with low weight from the nursery to market, increase the number of young animals marketed per sow, and increase calculated litter weight gain.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims priority to U.S. Provisional Application No. 62 / 855,600, filed May 31, 2019, the entire contents of which are incorporated herein by reference in their entirety. Technical Field

[0003] The present invention generally relates to methods of using therapeutic clays, formulations containing therapeutic clays, and methods of using therapeutic clays to improve performance in animals. Background Art

[0004] Many artificial growth promoters are widely used to control health challenges, improve lean tissue acquisition, and improve growth, performance and efficiency of feed utilization in livestock production. However, with the change of market demand, the use of artificial substances in livestock production has become less common. Therefore, the animal husbandry industry needs alternative technologies to manage its herd health and production efficiency in the absence of artificial growth promoters at all livestock growth production stages. Optimally, this alternative growth promoter will be easy to implement on the farm and provide multiple benefits for herd health and production from birth to market. Summary of the invention

[0005] One aspect of the present disclosure includes a method for improving reproductive and litter size performance of a maternal animal. The method includes orally administering to the animal an effective amount of a therapeutic clay. In some aspects, the animal is a pig.

[0006] The clay can be formulated in a feed composition for oral administration to an animal. The clay can be administered during pregnancy, lactation, and combinations thereof. For example, the clay can be administered for a period of time during pregnancy. In some aspects, the clay is administered from breeding to delivery. The clay can also be administered for a period of time during lactation. For example, the clay can be administered from delivery to weaning.

[0007] Improving reproduction performance can include reducing embryo loss, increasing litter size, increasing live birth number, improving the immune status of maternal animals, reducing the concentration of maternal feces amino acids, reducing the concentration of maternal feces short-chain amino acids and increasing birth litter weight.Improving the immune status of maternal animals can include the increase of IFNγ and TNF-α levels in maternal animals, and the reduction of TRAIL levels in maternal animals.In some aspects, the level of TNF-α before childbirth in maternal animals is positively correlated with total weaning, negatively correlated with subsequent stillbirth, and positively correlated with subsequent mummy.In some aspects, the level of TRAIL before childbirth is negatively correlated with subsequent total birth and subsequent survival birth.In some aspects, the level of weaning IFN-γ is positively correlated with total weaning.

[0008] Improving litter size performance may include increasing colostrum intake in young animals, reducing pre-weaning mortality in young animals, reducing the number of young animals lost due to low vitality, reducing the number of young animals weaned, improving the immune status of young animals at weaning, reducing the number of young animals with low weight from the nursery to market, increasing the number of young animals marketed per sow, and increasing calculated litter weight gain. The immune status of young animals may include total immunoglobulins in the blood.

[0009] The amount of clay in the feed composition may range from about 0.1 lb / ton to 10 lb / ton. The amount of clay in the gestation feed composition may range from about 0.5 lb / ton to 4.0 lb / ton. In addition, the amount of clay in the lactation feed composition may range from about 0.5 lb / ton to 0.8 lb / ton.

[0010] In addition, the amount of clay administered to the sow may be in the range of about 1.0 g / d to about 10 g / d, about 0.1 g / d to about 8 g / d, about 0.5 g / d to about 3 g / d, or about 4.0 g / d to about 7 g / d. In addition, when the animal is a pig, the clay may be administered starting from day 3 to day 93 of gestation.

[0011] Another aspect of the present disclosure includes a method of increasing piglet colostrum intake, reducing pre-weaning mortality, reducing the number of piglets lost due to low vitality, reducing the number of pigs weaned, reducing the number of underweight pigs from the nursery to market, increasing the number of pigs marketed per sow, and increasing calculated litter weight gain. The method comprises orally administering a therapeutically effective amount of clay to the sow. In some aspects, the sow is 2-parous or 6-parous or more.

[0012] The clay can be formulated in a feed composition for oral administration to an animal. The clay can be administered during pregnancy, lactation, and combinations thereof. For example, the clay can be administered for a period of time during pregnancy. In some aspects, the clay is administered from breeding to delivery. The clay can also be administered for a period of time during lactation. For example, the clay can be administered from delivery to weaning. In some aspects, when the animal is a pig, the clay is administered starting from day 3 to day 93 of pregnancy.

[0013] In some aspects, the amount of clay in the feed composition can be in the range of about 0.1 lb / ton to 10 lb / ton. For example, the amount of clay in the gestation feed composition can be in the range of about 0.5 lb / ton to 4.0 lb / ton. The amount of clay in the lactation feed composition can be in the range of about 0.5 lb / ton to 0.8 lb / ton.

[0014] The amount of clay administered to the sow may range from about 1.0 g / d to about 10 g / d, about 0.1 g / d to about 8 g / d, about 0.5 g / d to about 3 g / d, or about 4.0 g / d to about 7 g / d. In addition, when the animal is a pig, the clay may be administered starting from day 3 to day 93 of gestation.

[0015] Another aspect of the present disclosure includes methods of reducing embryonic loss, increasing litter size, increasing live births, improving the immune status of maternal animals, reducing the concentration of maternal fecal amino acids, reducing the concentration of maternal fecal short-chain amino acids, and increasing litter weight. The method includes orally administering an effective amount of a therapeutic clay to a sow. In some aspects, the sow is 2-parous or 6-parous or more.

[0016] The clay can be formulated in a feed composition for oral administration to an animal. The clay can be administered during pregnancy, lactation, and combinations thereof. For example, the clay can be administered for a period of time during pregnancy. In some aspects, the clay is administered from breeding to delivery. The clay can also be administered for a period of time during lactation. For example, the clay can be administered from delivery to weaning. In some aspects, the clay is administered starting from day 3 to day 93 of pregnancy.

[0017] In some aspects, the amount of clay in the feed composition can be in the range of about 0.1 lb / ton to 10 lb / ton. For example, the amount of clay in the gestation feed composition can be in the range of about 0.5 lb / ton to 4.0 lb / ton. The amount of clay in the lactation feed composition can be in the range of about 0.5 lb / ton to 0.8 lb / ton.

[0018] The amount of clay administered to the sow may range from about 1.0 g / d to about 10 g / d, about 0.1 g / d to about 8 g / d, about 0.5 g / d to about 3 g / d, or about 4.0 g / d to about 7 g / d. In addition, when the animal is a pig, the clay may be administered starting from day 3 to day 93 of gestation.

[0019] Yet another aspect of the present disclosure includes a method for enhancing litter size performance in pigs. The method includes orally administering an effective amount of therapeutic clay to a sow. In some aspects, the sow is 2-parous, or 6-parous or more.

[0020] Improving litter size performance can include increasing piglet colostrum intake, reducing pre-weaning mortality, reducing the number of piglets lost due to low vitality, reducing the number of pigs weaned, improving the immune status of piglets at weaning, reducing the number of light-weight piglets from the nursery to market, increasing the number of pigs marketed per sow, and increasing calculated litter weight gain.

[0021] The clay can be formulated in a feed composition for oral administration to an animal. The clay can be administered during pregnancy, lactation, and combinations thereof. For example, the clay can be administered for a period of time during pregnancy. In some aspects, the clay is administered from breeding to delivery. The clay can also be administered for a period of time during lactation. For example, the clay can be administered from delivery to weaning. In some aspects, the clay is administered starting from day 3 to day 93 of pregnancy.

[0022] In some aspects, the amount of clay in the feed composition can be in the range of about 0.1 lb / ton to 10 lb / ton. For example, the amount of clay in the gestation feed composition can be in the range of about 0.5 lb / ton to 4.0 lb / ton. The amount of clay in the lactation feed composition can be in the range of about 0.5 lb / ton to 0.8 lb / ton.

[0023] The amount of clay administered to the sow may range from about 1.0 g / d to about 10 g / d, about 0.1 g / d to about 8 g / d, about 0.5 g / d to about 3 g / d, or about 4.0 g / d to about 7 g / d. In addition, when the animal is a pig, the clay may be administered starting from day 3 to day 93 of gestation.

[0024] Another aspect of the present disclosure includes a method of enhancing reproductive performance of a sow, the method comprising administering to the sow an effective amount of a therapeutic clay. In some aspects, the sow is 2-parous, or 6-parous or more.

[0025] Improved reproductive performance may include reduced embryonic loss, increased litter size, increased live births, improved immune status of the maternal animal, reduced maternal fecal amino acid concentrations, reduced maternal fecal short-chain amino acid concentrations, and increased litter weights.

[0026] The clay can be formulated in a feed composition for oral administration to an animal. The clay can be administered during pregnancy, lactation, and combinations thereof. For example, the clay can be administered for a period of time during pregnancy. In some aspects, the clay is administered from breeding to delivery. The clay can also be administered for a period of time during lactation. For example, the clay can be administered from delivery to weaning. In some aspects, the clay is administered starting from day 3 to day 93 of pregnancy.

[0027] In some aspects, the amount of clay in the feed composition can be in the range of about 0.1 lb / ton to 10 lb / ton. For example, the amount of clay in the gestation feed composition can be in the range of about 0.5 lb / ton to 4.0 lb / ton. The amount of clay in the lactation feed composition can be in the range of about 0.5 lb / ton to 0.8 lb / ton.

[0028] The amount of clay administered to the sow may range from about 1.0 g / d to about 10 g / d, about 0.1 g / d to about 8 g / d, about 0.5 g / d to about 3 g / d, or about 4.0 g / d to about 7 g / d. In addition, when the animal is a pig, the clay may be administered starting from day 3 to day 93 of gestation.

[0029] One aspect of the present disclosure includes a method of improving litter size performance in pigs, the method comprising orally administering to a sow an effective amount of a therapeutic clay. Improving litter size performance may include increasing colostrum intake in young animals, reducing pre-weaning mortality in young animals, reducing the number of young animals lost due to low vitality, reducing the number of young animals weaned, improving the immune status of young animals at weaning, reducing the number of young animals that are underweight from the nursery to market, increasing the number of young animals marketed per sow, and increasing calculated litter weight gain.

[0030] The clay can be formulated in a feed composition for oral administration to an animal. The clay can be administered during pregnancy, lactation, and combinations thereof. For example, the clay can be administered for a period of time during pregnancy. In some aspects, the clay is administered from breeding to delivery. The clay can also be administered for a period of time during lactation. For example, the clay can be administered from delivery to weaning. In some aspects, the clay is administered starting from day 3 to day 93 of pregnancy.

[0031] In some aspects, the amount of clay in the feed composition can be in the range of about 0.1 lb / ton to 10 lb / ton. For example, the amount of clay in the gestation feed composition can be in the range of about 0.5 lb / ton to 4.0 lb / ton. The amount of clay in the lactation feed composition can be in the range of about 0.5 lb / ton to 0.8 lb / ton.

[0032] The amount of clay administered to the sow may range from about 1.0 g / d to about 10 g / d, about 0.1 g / d to about 8 g / d, about 0.5 g / d to about 3 g / d, or about 4.0 g / d to about 7 g / d. In addition, when the animal is a pig, the clay may be administered starting from day 3 to day 93 of gestation. DETAILED DESCRIPTION

[0033] The present disclosure relates to methods of using therapeutic clays to improve efficiency, growth and performance in animal production. Specifically, it was found that oral administration of therapeutic clays to animals improved reproductive performance and litter size performance in mammals. Surprisingly, administration of clays to maternal animals improved litter size performance even after the young animals were weaned, without administering clays to weaned animals. For example, administration of clays to maternal animals reduced the number of light-weight young animals from the nursery to market and increased the number of young animals marketed per sow, even when the animals were not given clays.

[0034] I. Therapeutic Clay

[0035] In one aspect, the present disclosure provides therapeutic clays. Clays are administered orally. In some aspects, the clays are formulated with other ingredients to facilitate oral administration and effective use. For example, the therapeutic clays can be formulated with nutritional or other agents for administration to animals. Clays and formulations containing therapeutic clays are described below.

[0036] A. Clay

[0037] As used herein, the term "clay" refers to fine-grained natural rock or soil material that combines one or more clay minerals with trace metal oxides and organic matter. Clay from natural geological clay deposits is mainly composed of silicate minerals that contain variable amounts of water trapped in the mineral structure. In addition, as will be appreciated by those skilled in the art, clay may further include various amounts of metal oxides, organic matter, and other materials that may be mixed with clay. Sometimes clay includes varying amounts of iron, magnesium, alkali metals, alkaline earth metals, and other cations. Depending on the content of the soil, clay may appear in various colors, from white to dark gray or brown to dark orange-red. Clay can be roughly divided into swelling clay, non-swelling clay, and mixed layer clay.

[0038] Any clay can be used in the compositions or methods of the present disclosure, provided that the clay has therapeutic properties. Without wishing to be bound by theory, the therapeutic properties of the clay may include antimicrobial properties, antitoxin properties, and other properties that may contribute to the therapeutic properties of the clay that are different from antimicrobial to antitoxin activity. In contrast, therapeutic clays may provide the desired therapeutic properties without having antimicrobial or antitoxin properties. In some aspects, therapeutic clays have clay therapeutic properties that are different from antimicrobial activity to antitoxin activity. Clays with therapeutic properties suitable for the methods of the present disclosure may be as described in U.S. Patent Application No. 15 / 266,570, the disclosure of which is incorporated herein by reference in its entirety.

[0039] In some aspects, the therapeutic clay can be combined with other clays. For example, the therapeutic clay can be combined with other clays in a ratio of about 1:99 therapeutic clay to other clays, to about 99:1 therapeutic clay to other clays; in a ratio of about 80:20 therapeutic clay to other clays, to about 30:70 therapeutic clay to other clays; or about 45:55 therapeutic clay to other clays. In some aspects, the therapeutic clay can be combined with bentonite clay.

[0040] The therapeutic clay can be a swelling clay, a non-swelling clay, a mixed layer clay, or a combination of swelling clay, non-swelling clay and mixed layer clay. In some aspects, the clay of the present disclosure is a swelling clay. Swelling or swelling clays are clays that are prone to large volume changes (swelling and shrinking) directly related to changes in water content. Swelling clays are generally called montmorillonite clays. Montmorillonite clays have 2:1 layers (c-direction of the unit cell) approximately 1 nm thick, which are separated by hydrated interlayer cations that cause the clay to swell. The "a" and "b" sizes of the mineral are on the order of a few microns. These layers themselves are composed of two opposing silicate sheets, the silicate sheets containing Si and Al tetrahedrally coordinated with oxygen, separated by octahedral sheets, the octahedral sheets containing Al, Fe and Mg octahedrally coordinated with hydroxyl groups. The surface of the 2:1 layer (octahedral sheet between two tetrahedral sheets) carries a net negative charge balanced by the interlayer cations. The charged surface of the 2:1 layer attracts cations and water, which results in swelling.

[0041] Montmorillonite clays can be classified according to the location of the negative charge on the 2:1 layer and based on the composition of the octahedral sheet (dioctahedral or trioctahedral). Dioctahedral montmorillonites include beidellites, which have most of the charge in the tetrahedral sheet, and montmorillonites, which have most of the charge in the octahedral sheet. Similar trioctahedral montmorillonites are saponites and hectorites. By exchanging the major interlayer cations, the swelling and other properties of montmorillonites can be altered. For example, by exchanging Na instead of Ca, swelling can be limited to 2 water layers.

[0042] Montmorillonite clay can be naturally mined. Alternatively, montmorillonite clay can be synthesized. Methods for synthesizing montmorillonite clay can be as described in U.S. Patent No. 4,861,584, the disclosure of which is incorporated herein by reference in its entirety.

[0043] In other aspects, the therapeutic clays of the present disclosure are non-swelling clays, also commonly referred to as illite clays. Illite clays are structurally similar to montmorillonite clays, but their 2:1 layers are held together by poorly hydrated potassium ions and therefore do not swell.

[0044] In a preferred aspect, the therapeutic clay of the present disclosure is a mixed layer clay. Mixed layer clays are often referred to as rectorites and consist of ordered mixed layers of illite and montmorillonite. The illite and montmorillonite layers in rectorite clays can be random or regular. The ordering of the illite and montmorillonite layers in rectorites can be referred to as R 0 Sort or R 1 Sorted illite-montmorillonite. 1 The sorted illite-montmorillonite is sorted in the ISISSIS manner, while R 0 Describes random ordering. Other advanced ordering types may also be described. In some aspects, the clays disclosed herein are those having R 1Rectorite with ordered layers of illite and montmorillonite.

[0045] The therapeutic clay of the present disclosure is K-rectorite. More preferably, the therapeutic clay is K-rectorite comprising a therapeutically effective amount of a reducing agent. Even more preferably, the therapeutic clay is K-rectorite comprising a therapeutically effective amount of pyrite, or comprising a therapeutically effective amount of Fe 3+ K-rectorite.

[0046] The therapeutic clay of the present disclosure can be an unrefined naturally occurring therapeutic clay. Alternatively, the clay can be a refined clay purified from other materials typically present in naturally occurring clay. In addition, the clay can be purified to provide a substantially single form of the therapeutic clay. For example, when the clay is a rectorite clay, the clay can be purified to provide substantially pure K-rectorite clay, substantially pure Na-rectorite clay, or substantially pure Ca-rectorite clay. In some aspects, the clay is a naturally occurring therapeutic clay. In other aspects, the therapeutic clay is a refined clay. In other aspects, the therapeutic clay is a purified clay.

[0047] In some aspects, the therapeutic clay is an unrefined, naturally occurring therapeutic clay. In another aspect, the clay is a refined, naturally occurring therapeutic clay. In other aspects, the clay is synthetic. Methods for synthesizing therapeutic clays can be as described in U.S. Patent Publication No. 2013 / 0004544, the disclosure of which is incorporated herein by reference in its entirety. In other aspects, the therapeutic clay is naturally mined, and the level of the reducing agent in the mined clay is adjusted to provide a therapeutically effective amount of the reducing agent in the clay.

[0048] In some aspects, the therapeutic clay of the present disclosure is a naturally mined clay from an open pit mine in a hydrothermally altered pyroclastic material in Cascade Mountain. Without wishing to be bound by theory, the therapeutic properties of the clay may be due to a rare transition metal combination including pyrite levels ranging from about 3% to about 10% wt / wt and / or pyrite levels ranging from about 1% to about 5% wt / wt.

[0049] In other aspects, the clay of the present disclosure is natural red clay mined in the Cascade Mountains of Oregon, more specifically red clay mined in the Pit Lake area of ​​the Cascade Mountains of Oregon. Without wishing to be bound by theory, the therapeutic properties of the red clay may be due to the presence of a therapeutically effective amount of aluminum as described above, among other properties.

[0050] Clays can also be modified with various substituents to change the performance of the clay. Non-limiting examples of modification include modification with organic materials, polymers, reducing agents and various elements such as sodium, iron, silver or bromide, or by treatment with strong acids. In some aspects, the clays of the present disclosure are modified with reducing metal oxides. In some alternatives, when the clay is modified with reducing metal oxides, the clay is modified with pyrite.

[0051] The particle size of clay may be an important factor that can affect its effectiveness and bioavailability, blending uniformity, separation and flow properties.Usually, clay of smaller particle size increases its effectiveness by increasing surface area.In various fields, the mean particle size of clay is a diameter less than about 500 microns, or a diameter less than about 450 microns, or a diameter less than about 400 microns, or a diameter less than about 350 microns, or a diameter less than about 300 microns, or a diameter less than about 250 microns, or a diameter less than about 200 microns, or a diameter less than about 150 microns, or a diameter less than about 100 microns, or a diameter less than about 75 microns, or a diameter less than about 50 microns, or a diameter less than about 25 microns, or a diameter less than about 15 microns.In some applications, it may be advantageous to use particles less than 15 microns in diameter.Preferably, the mean particle size of clay is a diameter of about 1 to about 200 microns, preferably a diameter of about 10 to about 150 microns.

[0052] Similarly, in aspects where a reducing agent may be added to the clay, the particle size of the reducing agent may also be an important factor that may affect its effectiveness, and generally, smaller particle sizes increase its effectiveness. Preferably, the average particle size of the reducing agent that may be added to the clay is less than 1 micron in size.

[0053] B. Dietary supplements or feed compositions containing therapeutic clay

[0054] One aspect of the invention provides a dietary supplement or feed composition comprising a therapeutically effective amount of a therapeutic clay. The effective amount of the therapeutic clay in the feed supplement composition can and will vary depending on the clay, the weight, sex, age and / or medical condition of the animal, the severity and extent of the infectious disease in the animal, the method of administration, the duration of treatment, and the species of the animal, and can be determined experimentally using methods known in the art.

[0055] Typically, the amount of therapeutic clay present in the feed or supplement composition will be at least 0.001% (w / w) of the total composition. In one aspect, the amount of clay in the composition ranges from about 0.001% to about 100% (w / w). For example, the amount of clay in the composition can be in the range of about 0.001% to about 50% (w / w), about 25% to about 75% (w / w), or about 50% to about 100% (w / w). Preferably, the amount of clay in the feed or supplement composition ranges from about 0.001% to about 15% (w / w), more preferably from about 0.1% to about 10% (w / w), and even more preferably from about 0.1% to about 0.5% (w / w).

[0056] The terms "feed," "food," "feed composition," and "feed supplement" are used interchangeably herein and may refer to any feed composition that is typically fed to animals. Feed compositions that are typically fed to animals are known in the art. A feed composition may include one or more components of an animal feed. Non-limiting examples of feed materials or animal feed materials may include, but are not limited to: corn or corn components, such as corn meal, corn fiber, corn hulls, corn DDGS (distillers dried grains with solubles), silage, ground corn, corn germ, corn gluten, corn oil, or any other part of a corn plant; soybeans or soybean components, such as soybean oil, soybean meal, soybean hulls, soybean silage, ground soybeans, or any other part of a soybean plant; wheat or any component of wheat, such as wheat flour, wheat fiber, wheat hulls, wheat bran, ground wheat, wheat germ, or any other part of a wheat plant; rapeseed, such as rapeseed oil, rapeseed meal, rapeseed protein, rapeseed hulls, ground rapeseed, or any other part of a rapeseed plant; sunflower or sunflower plant The feed composition may be a component of a plant, such as sorghum or a component of a sorghum plant; a component of a sugar beet or a component of a sugar beet plant; a component of a sucrose or sugar cane plant; a component of a barley or barley plant; a component of a palm oil, palm kernel or palm plant; glycerine; corn steep liquor; a waste stream from an agricultural processing facility; lecithin; a rumen-protected fat; molasses; soy molasses; flax; peanuts; peas; oats; grasses, such as ornithogalum and fescue; fish meal, meat and bone meal; feather meal; and poultry by-product meal; and alfalfa and / or alfalfa grass for silage or hay, and various combinations of any of the feed ingredients described herein, or other feed ingredients generally known in the art. As is recognized in the art, the feed composition may be further supplemented with amino acids, vitamins, minerals and other feed additives, such as other types of enzymes, organic acids, essential oils, probiotics, prebiotics, antioxidants, pigments, anti-caking agents, etc., as further described below.

[0057] Feed compositions can be formulated for administration to any animal subject. Suitable subjects include all mammals, birds and aquaculture. Non-limiting examples of edible animals include poultry (e.g., chickens, including broilers, laying hens and breeders, ducks, hens, geese, guinea fowl / hens, quail and turkeys), beef cattle, dairy cows, calves, pigs, goats, sheep, bison and fish. Suitable companion animals include, but are not limited to, cats, dogs, horses, rabbits, rodents (e.g., mice, rats, hamsters, gerbils and guinea pigs), hedgehogs and ferrets. Examples of research animals include rodents, cats, dogs, rabbits, pigs and non-human primates. Non-limiting examples of suitable zoo animals include non-human primates, lions, tigers, bears, elephants, giraffes, etc.

[0058] According to various aspects of the present invention, the feed can be in any suitable form known in the art of animal feed, and can be a wet or dry component. For example, according to certain aspects, the feed composition can be in a form selected from a complete feed, a feed supplement, a feed additive, a premix, a top-dress, a bath, a mineral, a diet, a block, a pellet, a mash, a liquid supplement, a drench, a bolus, a treat, and any combination thereof. In addition, the feed sample can be optionally ground prior to preparing the feed composition.

[0059] The dietary supplement or feed composition may optionally include at least one additional nutrition and / or medicament. For example, the at least one additional nutrition and / or medicament may be selected from vitamins, minerals, amino acids, antioxidants, probiotics, essential fatty acids and pharmaceutically acceptable excipients. The composition may include a combination of an additional nutrition and / or pharmaceutical component or any of the aforementioned additional components in varying amounts. Suitable examples of each additional component are described in detail below.

[0060] a. Vitamins

[0061] Optionally, the dietary supplement of the present invention may include one or more vitamins. Suitable vitamins for use in the dietary supplement include vitamin C, vitamin A, vitamin E, vitamin B12, vitamin K, riboflavin, niacin, vitamin D, vitamin B6, folic acid, pyridoxine, thiamine, pantothenic acid and biotin. The form of the vitamin may include a salt of the vitamin, a derivative of the vitamin, a compound with the same or similar activity as the vitamin, and a metabolite of the vitamin.

[0062] Dietary supplements can include any vitamin described herein or known in the art in an effective amount of one or more forms. Non-limiting examples of vitamins include vitamin K, vitamin D, vitamin C and biotin. The "effective amount" of vitamins is usually quantified as at least about 10% of the U.S. recommended daily allowance ("RDA") of the specific vitamin to the subject. However, it is expected that the amount of some vitamins may be beneficial to some subjects in excess of the RDA. For example, the amount of a given vitamin can exceed applicable RDA 100%, 200%, 300%, 400%, 500% or more.

[0063] b. Minerals

[0064] In addition to the metal chelates or metal salts described in Section IA, the dietary supplement may include one or more minerals or mineral sources. Non-limiting examples of minerals include, but are not limited to, calcium, iron, chromium, copper, iodine, zinc, magnesium, manganese, molybdenum, phosphorus, potassium, and selenium. Suitable forms of any of the foregoing minerals include soluble mineral salts, slightly soluble mineral salts, insoluble mineral salts, chelated minerals, mineral complexes, non-reactive minerals such as carbonyl minerals and reducing minerals, and combinations thereof.

[0065] In one aspect, the mineral can be in the form of calcium. Suitable calcium forms include calcium alpha-ketoglutarate, calcium acetate, calcium alginate, calcium ascorbate, calcium aspartate, calcium octanoate, calcium carbonate, calcium chelates, calcium chloride, calcium citrate, calcium citrate malate, calcium formate, calcium glucuronate, calcium gluceptate, calcium gluconate, calcium glutarate, calcium glycerophosphate, calcium lactate, calcium lysate, calcium malate, calcium orotate, calcium oxalate, calcium oxide, calcium pantothenate, calcium phosphate, calcium pyrophosphate, calcium succinate, calcium sulfate, calcium undecylenate, coral calcium, dicalcium citrate, dihydroxycalcium malate, dicalcium phosphate, and tricalcium phosphate.

[0066] In general, dietary supplements can include any mineral as described herein or known in the art in an effective amount of one or more forms. The "effective amount" of a mineral is usually quantified as at least about 10% of the U.S. recommended daily allowance ("RDA") of the specific mineral to a subject. However, it is expected that the amount of some minerals exceeding the RDA may be beneficial to some subjects. For example, the amount of a given mineral can exceed the applicable RDA100%, 200%, 300%, 400%, 500% or more. Typically, the amount of the mineral included in the dietary supplement can be about 1 mg to about 1500 mg, about 5 mg to about 500 mg or about 50 mg to about 500 mg per dose.

[0067] c. Essential fatty acids

[0068] Optionally, the dietary supplement may include a source of essential fatty acids. The essential fatty acids may be isolated, or they may be oil sources or fat sources containing essential fatty acids. On the one hand, the essential fatty acids may be polyunsaturated fatty acids (PUFAs), which typically have at least two carbon-carbon double bonds of cis configuration. PUFAs may be long-chain fatty acids with at least 18 carbon atoms. PUFAs may be ω-3 fatty acids, wherein the first double bond occurs in the third carbon-carbon bond from the methyl end of the carbon chain (i.e., relative to the carboxylic acid group). Examples of ω-3 fatty acids include alpha-linolenic acid (18:3, ALA), octadecatetraenoic acid (18:4), eicosatetraenoic acid (20:4), eicosapentaenoic acid (20:5; EPA), docosatetraenoic acid (22:4), n-3 docosapentaenoic acid (22:5; n-3DPA) and docosahexaenoic acid (22:6; DHA). PUFA can also be ω-5 fatty acid, wherein the first double bond occurs in the fifth carbon-carbon bond from the methyl end. Non-limiting examples of ω-5 fatty acids include myristoleic acid (14:1), myristoleate and myristoleic acid hexadecyl ester. PUFA can also be ω-6 fatty acid, wherein the first double bond occurs in the sixth carbon-carbon bond from the methyl end. Examples of ω-6 fatty acids include linoleic acid (18:2), γ-linolenic acid (18:3), eicosadienoic acid (20:2), dihomo-γ-linolenic acid (20:3), arachidonic acid (20:4), docosadienoic acid (22:2), adrenic acid (22:4) and n-6 ​​docosapentaenoic acid (22:5). Fatty acid can also be ω-9 fatty acid, such as oleic acid (18:1), eicosenoic acid (20:1), mere acid (20:3), erucic acid (22:1) and nervonic acid (24:1).

[0069] In another aspect, the essential fatty acid source can be an oil derived from marine products. Marine products can be fish or marine organisms of vertebrates, so that the oil can be fish oil or marine oil. Long-chain (20C, 22C) ω-3 and ω-6 fatty acids are found in marine products. The scope of the ratio of ω-3 to ω-6 fatty acids in marine products is about 8:1 to 20:1. Marine products from which the oil rich in ω-3 fatty acids can be obtained include but are not limited to abalone, scallops, white bass tuna, anchovies, catfish, clams, cod, gem fish, herring, trout, mackerel, herring, orange roughy, salmon, sardines, sea barracuda, sea bass, shark, shrimp, squid, trout and tuna.

[0070] On the other hand, the essential fatty acid source can be an oil of plant origin. Plants and vegetable oils are rich in ω-6 fatty acids. Some oils of plant origin, such as linseed oil, are particularly rich in ω-3 fatty acids. Plants or vegetable oils are usually extracted from the seeds of plants, but can also be extracted from other parts of plants. Plants or vegetable oils commonly used for cooking or seasoning include but are not limited to Brazilian palm oil, almond oil, amaranth oil, almond oil, argan oil, avocado oil, babassu oil, beech oil, black currant seed oil, borneol nut oil, borage seed oil, buffalo gourd oil, canola oil, carob oil, cashew oil, castor oil, coconut oil, coriander seed oil, corn oil, cottonseed oil, evening primrose oil, false flax oil, sesame ... The oil of vegetable origin may be hydrogenated or partially hydrogenated.

[0071] In yet another aspect, the essential fatty acid source can be an oil from algae. Commercially available algae-derived oils include those from Crypthecodinium cohnii and Schizochytrium sp. The algae-derived oils. Other suitable algae species from which oil can be extracted include Aphanizomenon flos-aquae, Bacilliarophys sp., Botryococcus braunii, Chlorophyceae sp., Dunaliella tertiolecta, Euglena gracilis, Isochrysis galbana, Nannochloropsissalina, Nannochloris sp., Neochloris oleoabundans, Phaeodactylum tricornutum, Pleurochrysis carterae, Prymnesium parvum, Scenedesmus dimorphus, Spirulinasp. and Tetraselmis chui.

[0072] d. Amino Acids

[0073] Dietary supplements can optionally include one to several amino acids. Suitable amino acids include alanine, arginine, asparagine, aspartic acid, cysteine, glutamine, glutamic acid, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine and valine or their hydroxy analogs. In some aspects, amino acid will be selected from essential amino acids. Essential amino acids are generally described as amino acids that can not be synthesized de novo by organisms, therefore must be provided in the diet. As non-limiting examples, people's essential amino acids include: L-histidine, L-isoleucine, L-leucine, L-lysine, L-methionine, L-phenylalanine, L-valine and L-threonine.

[0074] e. Antioxidants

[0075] The dietary supplement may include one or more suitable antioxidants. As will be appreciated by those skilled in the art, the suitability of a given antioxidant will vary depending on the type of dietary supplement to which it will be administered.Non-limiting examples of antioxidants include ascorbic acid and its salts, ascorbyl palmitate, ascorbyl stearate, isoketides, N-acetylcysteine, benzyl isothiocyanate, o-, m- or p-aminobenzoic acid (o- is anthranilic acid, p- is PABA), butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), caffeic acid, cantharidin, α-carotene, β-carotene (beta-carotene), β-carotene (beta-apo-carotenoic acid), carnosol, carvacrol, catechin, cetyl gallate, chlorogenic acid, citric acid and its salts, p-coumaric acid, curcumin, 3,4-dihydroxyacetic acid, N,N' -Diphenyl-p-phenylenediamine (DPPD), dilauryl thiodipropionate, distearyl thiodipropionate, 2,6-di-tert-butylphenol, dodecyl gallate, edetic acid, ellagic acid, isoascorbic acid, sodium isoascorbate, escin, esculetin, 6-ethoxy-1,2-dihydro-2,2,4-trimethylquinoline, ethyl gallate, ethyl maltol, ethylenediaminetetraacetic acid (EDTA), eugenol, ferulic acid, flavonoids, flavonoids (such as apigenin, chrysin, luteolin), flavonols (such as dacitin, myricetin, dandrolone), flavanones, frexin, fumaric acid, gallic acid, gentian extract, gluconic acid, glycine, guaiac gum, hesperidin, α-hydroxybenzylphosphonic acid, hydroxycinammic acid, hydroxyglutaric acid, hydroquinone, N-hydroxysuccinic acid, hydroxytyrosol, hydroxyurea, lactic acid and its salts, lecithin, lecithin citrate, R-α-lipoic acid, lutein, lycopene, malic acid, maltol, 5-methoxytryptamine, methyl gallate, monoglyceride citrate, monoisopropyl citrate, morin, β-naphthoflavone, nordihydroguaiaretic acid (NDGA), octyl gallate, oxalic acid, palmityl citrate, phenothiazine, phosphatidylcholine , phosphoric acid, phosphates, phytic acid, phytophenyl propene, propyl gallate, polyphosphates, quercetin, trans-resveratrol, rosmarinic acid, sesamol, silymarin, sinapic acid, succinic acid, stearyl citrate, syringic acid, tartaric acid, thymol, tocopherols (i.e., α-, β-, γ-, and δ-tocopherol), tocotrienols (i.e., α-, β-, γ-, and δ-tocotrienol), tyrosol, vanillic acid, 2,6-di-tert-butyl-4-hydroxymethylphenol (i.e., Ionox 100), 2,4-(tri-3',5'-di-tert-butyl-4'-hydroxybenzyl)-mesitylene (i.e., Ionox 330), 2,4,5-trihydroxybutyryl ketone, ubiquinone, tert-butylhydroquinone (TBHQ), thiodipropionic acid, trihydroxybutyrophenone, tryptamine, tyramine, uric acid, vitamin K and derivatives, vitamin Q10, zeaxanthin, or a combination thereof.

[0076] Natural antioxidants that can be included in dietary supplements include, but are not limited to, apple peel extract, blueberry extract, carrot juice powder, clove extract, coffee fruit, coffee bean extract, cranberry extract, eucalyptus extract, ginger powder, grape seed extract, green tea, olive leaf, parsley extract, mint, bell pepper extract, pomace, pomegranate extract, rice bran extract, rose hips, rosemary extract, sage extract, tart cherry extract, tomato extract, turmeric, and wheat germ oil.

[0077] f. Anti-inflammatory agents

[0078] The dietary supplement may optionally include at least one anti-inflammatory agent. In one aspect, the anti-inflammatory agent may be a synthetic nonsteroidal anti-inflammatory drug (NSAID), such as acetylsalicylic acid, diclofenac, indomethacin, oxametacin, ibuprofen, indoprofen, naproxen, ketoprofen, mefacic acid, analgin, piroxicam and celecoxib. On the other hand, the anti-inflammatory agent may be a prohormone that regulates the inflammatory process. Suitable prohormones with this property include prohormone convertase 1, proopiomelanocortin, prohormone B-type natriuretic peptide, SMR1 prohormone, etc. In another aspect, the anti-inflammatory agent may be an enzyme with anti-inflammatory effects. Examples of anti-inflammatory enzymes include bromelain, papain, silk peptide enzymes and proteolytic enzymes such as pancreatin (a mixture of trypsin, amylase and lipase).

[0079] In another aspect, the anti-inflammatory agent can be a peptide with an anti-inflammatory effect. For example, the peptide can be an inhibitor of phospholipase A2, such as anti-ampicillin-1, a peptide corresponding to amino acid residues 246-254 of lipocortin; anti-globulin-2, a peptide corresponding to amino acid residues 39-47 of uteroglobin; S7 peptide, which inhibits the interaction between interleukin 6 and interleukin 6 receptor; RP1, a prenyl protein inhibitor; and similar peptides. Alternatively, the anti-inflammatory peptide can be cortistatin, a cyclic neuropeptide associated with somatostatin, or a peptide corresponding to the N-terminal fragment of the SV-IV protein, the conserved region of E-, L- and P-selectin, etc. Other suitable anti-inflammatory preparations include collagen hydrolysates and milk micronutrient concentrates (e.g., MicroLactin® available from Stolle Milk Biologics, Inc., Cincinnati, OH), as well as milk protein hydrolysates, casein hydrolysates, whey protein hydrolysates, and vegetable protein hydrolysates.

[0080] In another aspect, the anti-inflammatory agent can be a probiotic that has been shown to modulate inflammation. Suitable immunomodulatory probiotics include lactic acid bacteria, such as Lactobacillus acidophilus, Lactobacillus and Bifidobacterium. In another aspect, the anti-inflammatory agent can be a plant extract with anti-inflammatory properties. Non-limiting examples of suitable plant extracts with anti-inflammatory benefits include blueberry, frankincense, catechu and skullcap, celery seed, chamomile, cherry, hookberry, eucalyptus, evening primrose, ginger, hawthorn, horsetail, catalpa bark, licorice, turmeric, white gecko, willow bark and yucca.

[0081] g. Probiotics

[0082] Probiotics and prebiotics can include yeasts and bacteria and small oligosaccharides that help establish immune protective rumen or intestinal microflora. As non-limiting examples, yeast-derived probiotics and prebiotics include components derived from yeast cell walls, such as beta-glucans, arabinoxylan isomaltose, agaro-oligosaccharides, lactulose, cyclodextrins, lactose, oligofructose, laminaria heptose, lactulose, beta-galacto-oligosaccharides, manno-oligosaccharides, raffinose, stachyose, oligofructose, glucosylsucrose, sucrose thermo-oligosaccharides, isomaltase, caramel, inulin and xylo-oligosaccharides. In one aspect, the yeast-derived agent can be beta-glucan and / or manno-oligosaccharides. Sources of yeast cell wall-derived components include Saccharomyces bisporus, Saccharomyces boulardii, Saccharomyces cerevisiae, Saccharomyces capsularis, Saccharomyces delbrueckii, Saccharomyces fermentati, Saccharomyces lugwigii, Saccharomyces microellipsoides, Saccharomyces pastorianus, Saccharomyces rosei, Candida albicans, Candida cloaceae, Candida tropicalis, Candida utilis, Geotrichum candidum, Hansenula americana, Hansenula anomala, Hansenula winei and Aspergillus oryzae.

[0083] Probiotics and prebiotics can also include factors derived from bacterial cell walls, such as peptidoglycans and other components from gram-positive bacteria with high peptidoglycan content. Exemplary gram-positive bacteria include Lactobacillus acidophilus, Bifedobact thermophilum, Bifedobat longhum, Streptococcus faecium, Bacillus pumilus, Bacillus subtilis, Bacillus licheniformis, Lactobacillus acidophilus, Lactobacillus casei, Enterococcus faecium, Bifidobacteriumbifidium, Propionibacterium acidipropionici, Propionibacteriium freudenreichii, and Bifidobacterium pscudolongum.

[0084] h. Herbs

[0085] As used herein, suitable herbs and herb derivatives refer to herb extracts, and materials derived from plants and plant parts such as leaves, flowers and roots, but are not limited thereto. Non-limiting exemplary herbs and herb derivatives include agrimony, alfalfa, aloe, amaranth, angelica, fennel, three needles, basil, bayberry, bee pollen, birch, bistort, blackberry, black cohosh, black walnut, thistle, blue cohosh, ivy, euphorbia, borage, bead, buckthorn, euphorbia, burdock, botanicals, pepper, coriander, cascara, nepeta, celery, cornflower, artichoke, chickweed, chicory, stone gall, clove, coltsfoot, comfrey, corn silk, thatch, verbena, cabbage root, cornflower, cornflower flower, dandelion, devil's needle grass, ledum, echinacea, elecampane, ephedra, eucalyptus, evening primrose, bright grass, false leaf, fennel, fenugreek, figwort, linseed, gentian, boxwood, ginger, ginseng, goldenseal, gotu kola, gum grass, hawthorn, hops, fur seal, horseradish, horsetail, walnut, hydrangea, hyssop, Iceland moss, Irish moss, jojoba, juniper, kelp, European peony, lemongrass, licorice, lobelia, mandrake, marigold, marjoram, marshmallow, mistletoe, marlin, mustard, myrrh, nettle, oat grass, Oregon grape, papaya, parsley, passionflower, peach, pennyroyal, mint, periwinkle, plantain, pleurisy root, pokeweed, prickly ash, plantain, quercetin, yew grass, red clover, red raspberry, red sedge, rhubarb, rose hip, rosemary, rue, safflower, saffron, sage, St. John's wort, willow, sassafras, saw palmetto, skullcap, polygala, senna, shepherd's purse, slippery elm, spearmint, spikenard, twin vine, Chinese tallow tree, strawberry, taheebo, thyme, uva ursi, valerian, violet, watercress, white oak bark, white pine bark, wild cherry, wild lettuce, wild yam, willow, wintergreen, witch hazel, white sandalwood, wormwood, yarrow, curly sorrel, santa, yucca, and combinations thereof.

[0086] i. Pigment

[0087] Suitable non-limiting pigments include actin erythromycin, alizarin, alloxanthin, β-apo-2'-carotene aldehyde, apo-2-lycopene, apo-6' - lycopene, astacein, astaxanthin, azafrinaldehyde, aacterioruberin, aixin, alpha-carotene, beta-carotene, gamma-carotene, beta-carotene, canthaxanthin, capsanthin, capsanthin, tartrazine, tartrazine, crocetin, crocetinsemialdehyde, crocin, chitosan, cryptoxanthin, alpha-cryptoxanthin, beta-cryptoxanthin, cryptomonaxanthin, cynthiaxanthin, deprenoxanthin, dehydroadonirubin, diatomaxanthin, 1,4-diamino-2,3-dihydroanthraquinone, 1,4-dihydroxyanthraquinone, 2,2'-Diketospirilloxanthi, eschscholtzxanthin, eschscholtzxanthone, flexixanthin, foliachrome, fucoxanthin, gazaniaxanthin, hexahydrolycopene, hopkinsiaxanthin, hydroxyspheriodenone,isofucoxanthin, loroxanthin, lutein, luteoxanthin, lycopene, phytoene, lycopene, lycopene, sakuanone, zeaxanthin, neochrome, neoxanthin, nonaprenoxanthin, OH-Chlorobactene, okenone, oscillaxanthin, paracentrone, pectenolone, pectenoxanthin, peridinin, phleixanthophyll, phoeniconone, phoenicopterone, phoenicoxanthin, physalien, phytofluene, pyrrhoxanthininol, quinones, rhodopin, rhodopinal, rhodopinol, rhodovibrin, rhodoxanthin, rubixanthone, saproxanthin,semi-α-carotenone, semi-β-carotenone,sintaxanthin, siphonaxanthin, siphonein, spheroidene, tangeraxanthin, torularhodin, torularhodin methyl ester, torularhodinaldehyde, torulene, 1,2,4-trihydroxyanthraquinone, triphasiaxanthin, trollichrome, vaucheriaxanthin, violaxanthin, wamingone, xanthin, zeaxanthin, alpha-zeaxanthin, and combinations thereof.

[0088] j. Pharmaceutical preparations

[0089] Suitable non-limiting pharmaceutically acceptable agents include acid / base unstable drugs, pH dependent drugs or weak acid or weak base drugs. Examples of acid unstable drugs include statins (e.g., pravastatin, fluvastatin and atorvastatin), antibiotics (e.g., penicillin G, ampicillin, streptomycin, erythromycin, clarithromycin and azithromycin), nucleoside analogs (e.g., dideoxyinosine (ddI or didanosine), dideoxyadenosine (ddA), dideoxycytosine (ddC)), salicylates (e.g., aspirin), digoxin, bupropion, pancreatic enzymes, midazolam and methadone. Drugs that are soluble only at acidic pH include nifedipine, emopirin, nicardipine, amosulalol, noscapine, propafenone, quinine, dipyridamole, josamycin, birovirolol, labetalol, nisoprost and metronidazole. Drugs that are weak acids include phenobarbital, phenytoin, zidovudine (AZT), salicylates (e.g., aspirin), propionic acid compounds (e.g., ibuprofen), indole derivatives (e.g., indomethacin), phenamic acid compounds (e.g., meclofenamic acid), pyrrolidine carboxylic acid compounds (e.g., tolmetin), cephalosporins (e.g., cephalothin, cephalosporin, cefazolin, cephradine, cefpiroxine, cefmandol, and cefoxitin), 6-fluoroquinolones, and prostaglandins. Weak base drugs include adrenergic agents (e.g., ephedrine, methamphetamine, phenylephrine, epinephrine, salbutamol, and terbutaline), cholinergic agents (e.g., physostigmine and neostigmine), anticonvulsants (e.g., atropine, methantheline, and papaverine), curariform agents In some embodiments, the drug may be a bisphosphonate or a bisphosphonate. In some embodiments, the drug may be a bisphosphonate or a bisphosphonate. In some embodiments, the drug may be a bisphosphonate or a bisphosphonate. In some embodiments, the drug may be a bisphosphonate or a bisphosphonate. The limiting examples of bisphosphonates include alendronate, ibandronate, risedronate, zoledronate, pamidronate, neridronate, olpadronate, etidronate, clodronate and tiludronate. Other suitable medicines include estrogen, selective estrogen receptor modulators (SERMs) and parathyroid hormone (PTH) medicine. In another aspect, the medicine can be an antimicrobial (antibiotic).Suitable antibiotics include aminoglycosides (e.g., amikacin, gentamicin, kanamycin, neomycin, netilmicin, streptomycin, and tobramycin), carbapenems (e.g., cloracandib), carbapenems (e.g., certapenem, imipenem, and meropenem), cephalosporins (e.g., cefdroxil, cefazolin, cephalexin, cefaclor, cefadroxil, cephalexin, cefoxitin, cefprozil, cefuroxime, cefixime, cefdinir, cefditorin, cefoperazone, cefotaxime, cefpodoxime, ceftazidime, ceftibuten, ceftizoxime, and ceftriaxone), macrolides (e.g., azithromycin, erythromycin, tricarcin, chlortetracycline, erythromycin, and trombopag), monobactams, penicillins (e.g., amoxicillin, ampicillin, carbenicillin, cloxacillin, dicloxacillin, nafcillin, oxacillin, penicillin G, penicillin V, piperacillin, and ticarcillin), peptides (e.g., bacitracin, colistin, and polymyxin B), quinolones (e.g., ciprofloxacin, enoxacin, gatifloxacin, levofloxacin, lomefloxacin, moxifloxacin, norfloxacin, ofloxacin, and trofloxacin), sulfonamides (e.g., mafenidone, sulfacetamide, sulfadiazine, sulfadiazine, sulfisoxazole, and trimethoprim-sulfamethoxazole), and In another aspect, the drug may be an antiviral protease inhibitor (e.g., amprenavir, fosamprenavir, indinavir, lopinavir / ritonavir, ritonavir, saquinavir, and nelfinavir). In another aspect, the drug may be a cardiovascular drug. Examples of suitable cardiovascular drugs include cardiotonic agents (e.g., digitalis (digoxin), ubidecarenone, and dopamine), vasodilators (e.g., nitroglycerin, captopril, dihydralazine, diltiazem, and isosorbide dinitrate), antihypertensives (e.g., alpha-methyldopa, chlortalidone, reserpine, cyclohexine ... loserpine, retinol, prazosin, phentolamine, felodipine, propranolol, pindolol, labetalol, clonidine, captopril, enalapril, and lisinopril), beta blockers (such as levobunolol, pindolol, timolol maleate, bisoprolol, carvedilol, and butamyl), alpha blockers (such as doxazosin, prazosin, phenoxybenzamine, phenamine, tamsulosin, alfozosin, and terazosin), calcium channel blockers (such as amlodipine, felodipine, nicardipine, nifedipine, nisoldipine, nitrendipine, lacidipine, lecanidipine, verapamil, gallopamil, and diltiazem), and anticoagulants (such as dipyridamole).

[0090] k. Excipients

[0091] In dietary supplement formulations, a variety of commonly used excipients can be selected based on compatibility with the active ingredients. Non-limiting examples of suitable excipients include agents selected from non-effervescent disintegrants, colorants, flavor modifiers, oral dispersants, stabilizers, preservatives, diluents, densifiers, lubricants, fillers, binders, taste masking agents, effervescent disintegrants, and any combination of these agents.

[0092] In one aspect, the excipient is a binder. Suitable binders include starch, pregelatinized starch, gelatin, polyvinyl pyrrolidone, cellulose, methylcellulose, sodium carboxymethyl cellulose, ethyl cellulose, polyacrylamide, polyvinyloxypyrrolidone, polyvinyl alcohol, C12-C18 fatty acid alcohol, polyethylene glycol, polyol, carbohydrate, oligosaccharide, polypeptide, oligopeptide and combination thereof. Polypeptide can be any amino acid arrangement within the range of about 100 to about 300,000 daltons.

[0093] In another aspect, the excipient can be a filler. Suitable fillers include carbohydrates, inorganic compounds and polyvinylpyrrolidone. As non-limiting examples, fillers can be di- and tri-basic calcium sulfate, starch, calcium carbonate, magnesium carbonate, microcrystalline cellulose, calcium hydrogen phosphate, magnesium carbonate, magnesium oxide, calcium silicate, talc, modified starch, lactose, sucrose, mannitol and sorbitol.

[0094] Excipients may include non-effervescent disintegrants. Suitable examples of non-effervescent disintegrants include starches such as corn starch, potato starch, pregelatinized and modified starches, sweeteners, clays such as bentonite, microcrystalline cellulose, alginates, sodium starch glycolate, gums such as agar, guar gum, locust bean gum, karaya gum, pecitin and tragacanth.

[0095] In another aspect, the excipient can be an effervescent disintegrant. As non-limiting examples, suitable effervescent disintegrants include a combination of sodium bicarbonate and citric acid and a combination of sodium bicarbonate and tartaric acid.

[0096] The excipients may contain a preservative. Suitable examples of preservatives include antioxidants, such as alpha-tocopherol or ascorbate, and antimicrobials, such as parabens, chlorobutanol or phenol.

[0097] In another aspect, the excipient may include a diluent. Suitable diluents include pharmaceutically acceptable sugars, such as sucrose, glucose, lactose, microcrystalline cellulose, fructose, xylitol, and sorbitol; polyols; starch; preformed direct compression diluents; and mixtures of any of the foregoing.

[0098] Excipients may include flavoring agents. The spices incorporated into the outer layer may be selected from synthetic flavor oils and flavoring aromatics and / or natural oils, extracts from plants, leaves, flowers, fruits, and combinations thereof. For example, these may include cinnamon oil, wintergreen oil, peppermint oil, clover oil, hay oil, anise oil, eucalyptus oil, vanilla oil, citrus oils such as lemon oil, orange oil, grape and grapefruit oil, fruit essences including apple, peach, pear, strawberry, raspberry, cherry, plum, pineapple and apricot.

[0099] In another aspect, the excipient may include a sweetener. As non-limiting examples, the sweetener may be selected from glucose (corn syrup), dextrose, invert sugar, fructose, and mixtures thereof (when not used as a carrier); saccharin and its various salts, such as sodium salt; dipeptide sweeteners, such as aspartame; dihydrochalcone compounds, glycyrrhizin; stevia (stevioside); chlorinated derivatives of sucrose, such as sucralose; sugar alcohols, such as sorbitol, mannitol, sylitol, etc.

[0100] In another aspect, the excipient can be a lubricant. Suitable non-limiting examples of lubricants include magnesium stearate, calcium stearate, zinc stearate, hydrogenated vegetable oils, sterotex, polyoxyethylene monostearate, talc, polyethylene glycol, sodium benzoate, sodium lauryl sulfate, magnesium lauryl sulfate, and light mineral oil.

[0101] The excipient may be a dispersion enhancer. Suitable dispersants may include starch, alginic acid, polyvinyl pyrrolidone, guar gum, kaolin, bentonite, purified lignocellulose, sodium starch glycolate, isoamorphous silicate and microcrystalline cellulose as a high HLB emulsifier surfactant.

[0102] According to this aspect, it may be desirable to provide a colorant in the outer layer. Suitable color additives include food, drug and cosmetic colors (FD & C), drug and cosmetic colors (D & C) or external drug and cosmetic colors (Ext. D & C). These colorants or dyes, together with their corresponding lakes, and certain natural and derived colorants, may be suitable for use in the present invention according to these aspects.

[0103] Excipients may include taste masking agents. Taste masking materials include, for example, cellulose hydroxypropyl ethers (HPC), such as Klucel®, Nisswo HPC and PrimaFlo HP22; low-substituted hydroxypropyl ethers (L-HPC); cellulose hydroxypropyl methyl ethers (HPMC) such as Seppifilm-LC, Pharmacoat®, Metolose SR, Opadry YS, PrimaFlo, MP3295A, Benecel MP824 and Benecel MP843; methylcellulose polymers such as Methocel® and Metolose®; ethylcellulose (EC) and mixtures thereof such as E461, Ethocel®, Aqualon®-EC, Surelease; polyvinyl alcohol (PVA) such as Opadry AMB; hydroxyethylcellulose such as Natrosol®; carboxymethylcellulose and salts of carboxymethylcellulose (CMC), such as Aualon®-CMC; copolymers of polyvinyl alcohol and polyethylene glycol, such as Kollicoat®, IR®; monoglycerides (Myverol), triglycerides (KLX), polyethylene glycol, modified food starch, acrylic acid polymers and mixtures of acrylic acid polymers with cellulose ethers, such as Eudragit® EPO, Eudragit® RD100 and Eudragit® E100; cellulose acetate phthalate; sepifilms, such as mixtures of HPMC and stearic acid, cyclodextrins, and mixtures of these substances. In other aspects, other taste masking materials contemplated are those described in U.S. Pat. Nos. 4,851,226, 5,075,114 and 5,876,759, each of which is incorporated herein by reference in its entirety.

[0104] In various aspects, the excipient can include a pH adjuster. In certain aspects, the pH adjuster can include sodium carbonate or sodium bicarbonate.

[0105] The dietary supplement or feed composition described in detail herein can be manufactured in one or more dosage forms. In one aspect, the dosage form will be an oral dosage form. Suitable oral dosage forms may include tablets, such as suspension tablets, chewable tablets, effervescent tablets or caplets; pills; powders, such as sterile packaged powders, dispensable powders and effervescent powders; capsules, including soft or hard gelatin capsules or non-animal derived polymers, such as hydroxypropyl methylcellulose capsules (i.e. HPMC) or pullulan; lozenges; sachets; sprayers; reconstructible powders or mixed drinks; lozenges; granules; particles; liquids; lick blocks; suspensions; emulsions; or semisolids and gels. Alternatively, the dietary supplement may be incorporated into food or powders to mix with liquids, or may be administered orally only after mixing with non-food liquids. As will be appreciated by those skilled in the art, in addition to being suitable for administration in a variety of dosage forms, the dietary supplement may also be administered in various dosage regimens. In addition, therapeutic clays may be simply added to any dosage form of dietary supplement or feed composition.

[0106] The amounts and types of ingredients (i.e., metal chelates, chondroprotectants, vitamins, minerals, amino acids, antioxidants, yeast cultures, and essential fatty acids), as well as other excipients that may be used in each of these dosage forms are described throughout the specification and examples. It should be appreciated that when a combination of ingredients and / or excipients, including specific amounts of these components, is described with one dosage form, the same combination may be used in any other suitable dosage form. In addition, it should be understood that those skilled in the art, in accordance with the teachings in this application, can prepare any of the dosage forms listed above by combining the amounts and types of ingredients to be administered as a combination in a single dosage form or in separate dosage forms and administering together as described in different parts of the specification.

[0107] The dietary supplements of the present invention can be manufactured by conventional pharmacological techniques. Conventional pharmacological techniques include, for example, one or a combination of the following methods: (1) dry mixing; (2) direct compression; (3) grinding; (4) dry or non-aqueous granulation; (5) wet granulation; or (6) fusion. See, for example, Lachman et al., The Theory and Practice of Industrial Pharmacy (1986). Other methods include, for example, granulation, spray drying, pan coating, melt granulation, Wurster coating, tangential coating, top spraying, extrusion, coacervation, etc.

[0108] II. How to use

[0109] Another aspect of the present disclosure provides a method of orally administering an effective amount of a therapeutic clay to an animal. An effective amount of a therapeutic clay is any amount of clay that, when administered to an animal, will improve the performance of the animal compared to the performance of an animal fed a control diet without the clay. Clay or any combination of clay and other ingredients can be used for oral administration.

[0110] Any oral administration method can be used as long as the method is a controlled administration method that can administer a precise amount of clay to the animal. For example, the clay can be administered by spraying a precise amount of clay on the feed composition (top-up) or by adding to drinking water to administer a precise amount of clay when the animal ingests the feed or water. Alternatively, the clay can be formulated with the feed composition to administer a precise amount of clay when the animal ingests the feed composition.

[0111] Animals can include, but are not limited to, companion animals, such as cats, dogs, rabbits, horses, and rodents, such as gerbils; agricultural animals, such as dairy cows, suckling calves, beef cattle, pigs, goats, sheep, horses, deer; zoo animals, such as primates, elephants, zebras, big cats, bears, etc.; research animals, such as rabbits, sheep, pigs, dogs, primates, mice, rats, and other rodents; birds, including but not limited to chickens, ducks, turkeys, ostriches, and emus; and aquatic animals selected from fish and crustaceans, including but not limited to salmon, shrimp, carp, tilapia, and crustaceans.

[0112] In some aspects, the animal is a livestock animal. The term "livestock" as used herein refers to domesticated animals raised in an agricultural environment to produce labor and daily necessities such as meat, eggs, milk, fur, leather and wool. The term "livestock" can be used to refer only to animals raised for consumption. The term can also be used to refer only to farmed mammals, such as cattle, sheep, horses, pigs and goats. In some aspects, the animal is a pig.

[0113] The method comprises orally administering to the animal an effective amount of a therapeutic clay. As used herein, the phrase "effective amount" is intended to define an amount of an agent or compound that, when administered, will achieve the purpose of improving the performance of an animal compared to the performance of an animal fed a control diet not containing the agent or compound.

[0114] The time and duration of administration of the clay of the present invention to an animal can vary and will vary. For example, the clay can be routinely administered throughout the period of animal rearing. The clay can be administered at different intervals. For example, the clay can be administered daily, weekly, monthly, or over several months. In some aspects, the clay is administered daily. In other aspects, the clay is administered weekly. In still other aspects, the clay is administered monthly. The clay can also be administered once every three to six months. As is known in the art, the duration of treatment can vary and can be determined experimentally.

[0115] Clay can be given to animals in single doses or multiple doses throughout the administration period. For example, a single dose of clay can be given after reproduction, during pregnancy, at birth, or after farrowing. Alternatively, multiple doses of clay can be given during pregnancy, lactation, and combinations thereof. For example, the administration of clay can begin after mating and continue until the end of lactation. In some aspects, clay is given from reproduction to delivery. For example, when the animal is a pig, clay can be given three weeks before delivery or on the 110th, 111th, 112th, 113th, or 114th day of pregnancy. In some aspects, clay is given from delivery to weaning. Clay can also be given throughout the lactation period. In some aspects, clay is given throughout the gestation period and lactation period.

[0116] In some aspects, the clay is orally administered to an animal by adding the clay to a feed, formulating the clay with a feed or a supplement formulation, and feeding the feed or supplement formulation to the animal. Formulating the clay with the raw materials can be as described in Section B above.

[0117] When administered to an animal with a feed or supplement formulation, the amount of clay in the feed composition may be in the range of about 0.1 lb / ton to about 10 lb / ton. For example, the amount of clay in the feed composition may be in the range of about 0.5 lb / ton to about 2.0 lb / ton. Alternatively, the amount of clay in the feed composition may be in the range of about 0.4 lb / ton to about 0.6 lb / ton. The amount of clay in the gestation feed composition may be in the range of about 0.5 lb / ton to about 6.0 lb / ton. In some aspects, the amount of clay in the gestation feed composition is in the range of about 0.5 lb / ton to about 4.0 lb / ton. The amount of clay in the lactation feed composition may be in the range of about 0.5 lb / ton to about 6 lb / ton. In some aspects, the amount of clay in the lactation feed composition is in the range of about 1 lb / ton to about 2 lb / ton.

[0118] As will be appreciated by those skilled in the art, dosages of the compositions of the invention can and will vary depending on the animal, the frequency and timing of dosing, the weight, sex, age and / or medical condition of the animal, the desired growth rate and efficacy, the method of administration, and the duration of treatment.

[0119] The rate of administration of the clay of the present disclosure can depend on the level of the reducing agent in the clay. For example, the level of the reducing agent in the clay can be determined before administration to adjust the level of clay that can be used. The redox potential of the clay can be determined, and the level of the clay used in the method, composition or formulation of the present disclosure can be adjusted based on the redox potential of the clay. The redox potential of the clay can provide a general measure of the therapeutic potential of the clay, which can be used without considering the reducing agent present in the clay. Alternatively, the content of one or more specific reducing agents in the clay can be determined.

[0120] In some aspects, the amount of clay given to the maternal animal can be in the range of about 1.0 g / d to about 10 g / d, about 0.1 g / d to about 8 g / d, about 0.5 g / d to about 3 g / d, or about 4.0 g / d to about 7 g / d. In some aspects, the amount of clay given to the maternal animal is in the range of about 0.1 g / d to about 5 g / d. Clay can be given to the animal at a rate of about 0.5 g / d to about 3 g / d during pregnancy. Alternatively, clay can be given to the animal at a rate of about 4.0 g / d to about 5 g / d during lactation. In addition, when the animal is a pig, clay can be given starting from about the 1st day to about the 100th day of pregnancy.

[0121] Administration of a therapeutically effective amount of clay improves the reproductive performance and litter size performance of an animal. As used herein, the term "reproductive performance" refers to any aspect of an animal's health and well-being that can significantly affect the reproduction of the animal. For example, reproductive performance can be measured by the health and vitality of the animal, thereby making the animal more suitable for reproduction and production of healthy animals, by the number of offspring produced by the animal, and by the general health and vitality of the offspring produced by the animal. For example, when clay is administered to sows, the number of pigs born weighing less than 1.7 lbs can be significantly reduced.

[0122] As used herein, the term "litter size performance" refers to any aspect of the health and well-being of a litter mother given clay that can significantly affect the reproduction of the animal. It should be noted that when referring to litter size performance after weaning, the improvement in performance is a result of giving clay to the mother. Thus, litter size of animals given clay will have improved performance after weaning when the animals are not given clay.

[0123] In some aspects, administering a therapeutically effective amount of clay improves reproductive performance. Improving reproductive performance can include reducing embryonic loss, promoting pregnancy, increasing litter size, increasing live births, improving the immune status of maternal animals, reducing fecal amino acid concentrations, reducing fecal short-chain amino acid concentrations, and increasing litter weights.

[0124] Improving the immune status of maternal animals can include the increase of IFNγ and TNF-α levels in maternal animals, and the reduction of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) levels in maternal animals. In some respects, the level of TNF-α before farrowing in maternal animals is positively correlated with total weaning, negatively correlated with subsequent stillbirth, and positively correlated with subsequent mummy. In some respects, the level of TRAIL before parturition is negatively correlated with subsequent total birth and subsequent survival birth. In some respects, the level of weaning IFN-γ is positively correlated with total weaning.

[0125] In some aspects, administering a therapeutically effective amount of clay improves performance. Improving litter size performance may include increasing colostrum intake in young animals, reducing pre-weaning mortality in young animals, reducing the number of young animals lost due to low vitality, reducing the number of young animals weaned, improving the immune status of young animals at weaning, reducing the number of young animals that are underweight from the nursery to market, increasing the number of young animals marketed per sow, and increasing calculated litter weight gain. Immune status may include total immunoglobulins in the blood.

[0126] A. Improve pig performance.

[0127] Another aspect of the invention includes a method of increasing piglet colostrum intake, reducing pre-weaning mortality, reducing the number of piglets lost due to low viability, reducing the number of pigs weaned, reducing the number of underweight pigs from the nursery to market, increasing the number of pigs marketed per sow, and increasing calculated litter weight gain. The method comprises orally administering to the sow an effective amount of a therapeutic clay. In some aspects, the sow is 2-parous or 6-parous or more.

[0128] The clay may be as described in Section I (A) and the clay formulation may be as described in Section I (B) above.

[0129] The clay can be administered during pregnancy, during lactation, and combinations thereof. For example, the clay can be administered for a period of time during pregnancy. In some aspects, the clay is administered from reproduction to delivery. The clay can also be administered for a period of time during lactation. For example, the clay can be administered from delivery to weaning. In some aspects, the clay is administered starting from day 3 to day 93 of pregnancy.

[0130] In some aspects, the amount of clay in the feed composition can be in the range of about 0.1 lb / ton to 10 lb / ton. For example, the amount of clay in the gestation feed composition can be in the range of about 0.1 lb / ton to 4.0 lb / ton. The amount of clay in the lactation feed composition can be in the range of about 1.0 lb / ton to 2.0 lb / ton.

[0131] The amount of clay given to the sow can be about 1.0 g / d to about 10 g / d, about 0.1 g / d to about 8 g / d, about 0.5 g / d to about 3 g / d, or about 4.0 g / d to about 7 g / d. In addition, the clay can be given starting three weeks after breeding, or on days 3 to 93 of gestation.

[0132] Another aspect of the present disclosure includes methods of reducing embryonic loss, increasing litter size, increasing live births, improving the immune status of sows, reducing the concentration of fecal amino acids in sows, reducing the concentration of maternal fecal short-chain amino acids, and increasing litter weight. The method includes orally administering an effective amount of a therapeutic clay to a sow. In some aspects, the sow is 2-parous or 6-parous or more.

[0133] Yet another aspect of the present disclosure includes a method for enhancing litter size performance of pigs. The method includes orally administering an effective amount of a therapeutic clay to a sow. In some aspects, the sow is 2-parous, or 6-parous or more. Improving litter size performance may include increasing piglet colostrum intake, reducing pre-weaning mortality, reducing the number of piglets lost due to low vitality, reducing the number of pigs weaned, improving the immune status of piglets at weaning, reducing the number of piglets that are underweight from the nursery to market, increasing the number of pigs marketed per sow, and increasing calculated litter weight gain.

[0134] One aspect of the present disclosure includes a method of improving litter size performance in pigs, the method comprising orally administering to a sow an effective amount of a therapeutic clay. Improving litter size performance may include increasing piglet colostrum intake, reducing piglet pre-weaning mortality, reducing the number of piglets lost due to low viability, reducing the number of weaned piglets, improving the immune status of piglets at weaning, reducing the number of underweight young animals from the nursery to market, increasing the number of piglets marketed per sow, and increasing calculated litter weight gain.

[0135] definition

[0136] When introducing elements of the present disclosure, the articles "a," "an," "the," and "said" are intended to indicate that there are one or more elements, unless otherwise specified, the use of "or" means "and / or," and further, the use of the term "include" and other forms, such as "includes" and "comprising," are not limiting. Also, terms such as "element" or "component" encompass elements and components comprising one unit as well as elements and components comprising more than one subunit, unless expressly specified otherwise.

[0137] Unless otherwise defined herein, scientific and technical terms used in conjunction with the present disclosure shall have the meanings commonly understood by those of ordinary skill in the art. However, in the event of any potential ambiguity, the meaning and scope of the terms shall be clear, and the definitions provided herein shall take precedence over any dictionary or external definitions. In addition, unless the context otherwise requires, as used herein and in the claims, singular terms shall include the plural, and plural terms shall include the singular.

[0138] Where a numerical range is provided, it is to be understood that, unless the context clearly indicates otherwise, each intermediate value between the upper and lower limits of the range is also specifically disclosed, to one tenth of the lower limit unit. Each smaller range between any stated value or intermediate value in the stated range and any other stated value or intermediate value in the stated range is included in the present invention. The upper and lower limits of these smaller ranges may be independently included in or excluded from the range, and each range in which either limit, both limits are not included in the smaller range is also included in the present invention, subject to any specifically excluded limits in the stated range. When the stated range includes one or two limits, the range excluding one or both of those included limits is also included in the present invention.

[0139] As used herein, the terms "about" and "approximately" indicate that a value is within a statistically significant range. Such a range may typically be within 20%, more typically still within 10%, and even more typically within 5% of a given value or range. The allowable variations encompassed by the terms "about" and "approximately" depend on the specific system under study and can be readily understood by one of ordinary skill in the art.

[0140] As used herein, "administering" is used in its broadest sense to mean contacting a subject with a composition disclosed herein, provided that the method is a controlled administration method capable of administering a precise amount of clay to the animal.

[0141] The phrase "effective amount" is used to refer to an intended defined amount of an agent or compound which, when administered, will achieve the goal of improving the performance of an animal as compared to the performance of an animal fed a control diet not containing the agent or compound.

[0142] As used herein, the term "w / w" refers to the phrase "by weight" and is used to describe the concentration of a particular substance in a mixture or solution.

[0143] As used herein, the term "subject" refers to vertebrate species, such as mammals, birds, reptiles, amphibians and fish. The vertebrate species can be embryonic, juvenile or adult. Examples of suitable mammals include, but are not limited to, rodents, companion animals or livestock, livestock and primates. Non-limiting examples of rodents include mice, rats, hamsters, gerbils and guinea pigs. Non-limiting examples of livestock include goats, sheep, pigs, cattle, llamas and alpacas. Suitable primates include, but are not limited to humans, capuchin monkeys, chimpanzees, lemurs, macaques, marmosets, rhesus monkeys, spider monkeys, squirrel monkeys and prairie monkeys. Non-limiting examples of birds include chickens, turkeys, ducks and geese.

[0144] As used herein, the term "companion animal" or "livestock" refers to an animal that is typically kept as a pet to be kept near a home or domestic environment for company or protection, regardless of whether the animal is kept indoors or outdoors. Non-limiting examples of companion animals or livestock include, but are not limited to, dogs, cats, rabbits, ferrets, and horses.

[0145] The terms "isolated," "purified," or "biologically pure" refer to a material that is substantially or essentially free of components that normally accompany it in its native state. Purity and homogeneity are typically determined using analytical chemistry techniques such as polyacrylamide gel electrophoresis or high performance liquid chromatography. In other aspects, "purification" or "purification" refers to the removal of at least one contaminant from the composition to be purified. Purification in this sense does not require that the purified compound be homogeneous, e.g., 100% pure.

[0146] As various changes could be made in the above elements and methods without departing from the scope of the invention, it is intended that all matter contained in the above description and examples given below shall be interpreted as illustrative and not in a limiting sense. Example

[0147] All patents and publications mentioned in this specification are indicative of the levels of those skilled in the art to which the present disclosure pertains. All patents and publications are herein incorporated by reference to the same extent as if each individual publication was specifically and individually indicated to be incorporated by reference.

[0148] The publications discussed in their entireties are provided solely for their disclosure prior to the filing date of the present application. Nothing herein is to be construed as an admission that the present invention is not entitled to antedate such publication by virtue of prior invention.

[0149] The following examples are included to illustrate the present disclosure. It will be appreciated by those skilled in the art that the techniques disclosed in the following examples represent techniques that the inventors have found to work well in the practice of the present disclosure. However, it will be appreciated by those skilled in the art that, in accordance with the present disclosure, many changes may be made to the present disclosure without departing from the spirit and scope of the present disclosure and still obtaining the same or similar results, and therefore, all contents set forth shall be interpreted as illustrative rather than restrictive.

[0150] Example 1: Relationship between proinflammatory cytokines and litter size

[0151] Thirty-five sows (17 fed a control diet and 18 fed a diet containing clay) were used to determine the effect of feeding clay with pro-inflammatory cytokines. Blood samples were collected on gestational day 113 and again on lactation days 18-19. Serum samples were analyzed to determine circulating levels of tumor necrosis factor alpha (TNF-α), interferon gamma (INF-γ), and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Sow reproductive measurements and litter size were collected from littermates immediately after treatment with clay in the feed and from subsequent littermates after treatment of the littermates.

[0152] Data were transformed prior to analysis because serum cytokine levels were not normally distributed. A Box-Cox transformation was used on serum cytokine data to produce a normal distribution. Data were then analyzed to determine mean differences, and correlation analysis was performed to correlate serum cytokine levels with sow performance data.

[0153] parameter Conversion IFN-γ before delivery ^(0.25) TNF-α before delivery ^(-0.25) TRAIL before delivery ^(-0.25) Weaning IFN-γ ^(0.25) Weaning TNF-α ^(-0.25) Weaning TRAIL ^(-0.50)

[0154] Sows fed a diet including clay had increased total births, live births, and number of pigs weaned immediately after consuming the clay-based diet (Table 1). In addition, sows fed the clay-based diet subsequently had increased total births and live births compared to sows fed the control diet. Sows fed the clay-based diet had increased serum IFNγ and decreased TRAIL compared to sows fed the control diet, indicating that feeding clay has a positive effect on sows controlling inflammation and resulting litter weight gain.

[0155] Correlation analyses showed that increased IFNγ and decreased TRAIL were associated with increased litter size and decreased mummies in both immediate and subsequent littermates (Table 2). Antepartum TNF-α was positively associated with total weaning (P = 0.0838), negatively associated with subsequent stillbirth (P = 0.0789), and positively associated with subsequent mummies (P = 0.0356). Congenital TRAIL was negatively associated with subsequent total birth (P = 0.0062) and birth alive (P = 0.0062). Weaning IFN-γ was positively associated with total weaning (P = 0.0779). Weaning TNF-α was negatively associated with subsequent stillbirth (P = 0.0482), and positively associated with subsequent mummies (P = 0.0141). Weaning TRAIL was negatively associated with subsequent birth survival (P = 0.1067).

[0156] Table 1. ANOVA analysis evaluating differences between sows fed a control or clay-containing diet during gestation and lactation

[0157]

[0158] Table 2. Correlation analysis to assess the linear relationship between sow reproductive performance and biomarkers

[0159]

[0160]

[0161] Example 2: Effect of dietary clay fed to sows three weeks prior to farrowing

[0162] Experimental design, procedures, and data collection

[0163] Animal enclosures

[0164] Sows were housed individually in gestation pens after mating and were fed once a day throughout gestation via feed / water troughs based on their individual body condition scores. Water was available ad libitum. At approximately d 112 of gestation, sows were moved to farrowing pens and randomly placed in farrowing pens. The diet was changed from gestation to lactation diet and was fed ad libitum throughout lactation.

[0165] Diet therapy

[0166] Diet treatment was started about 93 days after mating. Every 10 sows located in adjacent stalls were considered as a subgroup. On the first day of the experiment, each subgroup was randomly assigned to one of 2 treatments, wherein the topdressing of the product was provided for treatment 2 (Table 3). A non-test sow was placed between each group to prevent the mixing of the experimental diet. In order to identify the treatment, each test sow was marked on the corner of their sow ID card using a spray marker according to the color they were assigned.

[0167] Table 3. Dietary treatments and assigned colors for sows.

[0168]

[0169] Experimental diet

[0170] The basal diet (Table 4) was a standard gestation and lactation diet without the addition of yeast or other clay-based technologies. Treatment 2 was delivered to sows by topdressing using a designated teaspoon. Topdressing was performed daily in late gestation by dripping the product in front of the feed / water trough at a prescribed rate when feeding in the morning. Air was purged prior to water delivery.

[0171] Topdress product daily at the lactation-specified rate after farrowing and throughout lactation until weaning. On the day of weaning, return the sows to the gestation barn and monitor the days from weaning to estrus.

[0172] Table 4: Dietary composition of the basal diet

[0173]

[0174] 1 Diet updated May 19, 2016.

[0175] Data Collection

[0176] Reproduction and litter size performance:

[0177] Body weights of individual sows were measured (1) on the day the sow was transferred to the farrowing crate, and (2) at weaning. The data were used to calculate weight loss during lactation using the following formula: Sow BW loss = Weaning - (PRE - (LW + LW / 5.5)), where Weaning = sow weight at weaning; PRE = sow pre-farming weight; LW = litter weight; LW / 5.5 = estimated placental weight. The number of days in lactation and the number of days from weaning to estrus were recorded. During lactation, sow feed intake was measured by the Gestal Solo system for at least 20 sows / treatment (at least 40 sows were measured). The number of piglets born per litter (live and dead), individual birth weight (live and dead), individual weaning weight, and the number of piglets that died during lactation were recorded. Cross-housing and removal of non-suckling pigs were performed only within the treatment period or to non-experimental littermates within 24 days after birth.

[0178] Statistical analysis

[0179] Data were analyzed using ANOVA with the MIXED procedure of SAS. Sows / litter served as the experimental unit. The statistical model included the fixed effect of dietary treatment and the covariate of litter number. Multiple comparisons between treatments were performed using the Tukey adjustment option of SAS. All results are reported as least squares means. The significance level chosen was α = 0.05. Treatment effects were considered significant if P < 0.05, and values ​​of 0.05 ≤ P ≤ 0.10 were considered statistical trends.

[0180] result

[0181] Sows fed the clay-containing diet had higher (P < 0.05) number of pigs born alive, litter size, calculated total weaning weight, calculated litter weaning weight, and calculated litter weight gain compared to sows fed the control diet, without changes in sow BW (Table 5). Sows fed the clay-containing diet had a lower (P < 0.05) percentage of mummies compared to sows fed the control diet. Sows fed the clay-containing diet tended (0.05 < P < 0.10) to have more total pigs born and an increase in calculated litter size with changes in sow BW.

[0182] Summarize

[0183] The objective of this trial was to determine the effects of feeding clay at 2.0 lb / ton during late gestation and lactation on sow and litter size performance and fecal shedding of E. coli in sows compared to sows fed a basal diet. Feeding clay at 2.0 lb / ton had a positive and significant effect on live pigs born, percent mummies, litter birth weight, number weaned, and litter gain calculations. Adding clay to the sow diet did not negatively affect any of the measurements, and there were no treatment differences in fecal measurements.

[0184] Table 5. Effects of feeding clay on reproductive performance of sows

[0185]

[0186]

[0187]

[0188] 1 During gestation and lactation, feed 2 lb / ton of complete feed, loosely spread over clay soil. Topdressing begins on day 93 of gestation and continues throughout lactation.

[0189] 2 Number of live births used as covariates in statistical models

[0190] 3 Calculated total weaning = birth survival x (1-PWM / 100)

[0191] 4 Suckling length used as a covariate in statistical models

[0192] 5 Calculated litter weaning weight = pig weaning wt x calculated total weanings

[0193] 6 No samples had detectable levels of F18 counts

[0194] 7 One sample from the control treatment and three samples from the clay treatment had detectable levels of F18 counts.

[0195] Example 3: Effect of clay supplementation in the diet of gestating and lactating sows on reproductive performance and litter size

[0196] Experimental design, procedures, and data collection

[0197] Animal enclosures

[0198] Sows were housed individually in gestation pens after mating and were fed once a day throughout gestation via feed / water troughs based on their individual body condition scores. Water was available ad libitum. At approximately d 112 of gestation, sows were moved to farrowing pens and randomly placed in farrowing pens. The diet was changed from gestation to lactation diet and was fed ad libitum throughout lactation.

[0199] Diet therapy

[0200] Diet treatment was started approximately 94 days after mating. Every 10 sows located in adjacent stalls were considered a subgroup. On the first day of the experiment, each subgroup was randomly assigned to one of 4 treatments, wherein topdressing of the product was provided to treatments 2 to 4 (Table 6). A non-test sow was placed between each group to prevent mixing of the experimental diets.

[0201] Table 6. Dietary treatments and assigned colours for sows.

[0202]

[0203] Experimental diet

[0204] The basal diet (Table 7) was a standard gestation and lactation diet. Treatments 2 to 4 were delivered to sows by topdressing using a designated teaspoon. In late gestation, topdressing was performed daily by dripping the product in front of the feed / water trough at a specified rate when feeding in the morning. Air was purged before water delivery.

[0205] Topdress product daily at the lactation-specified rate after farrowing and throughout lactation until weaning. On the day of weaning, return the sows to the gestation barn and monitor the days from weaning to estrus.

[0206] Table 7. Dietary composition of the basal diet

[0207]

[0208] 1 The diet consisted of 400 ppm CTC and 35 ppm Denagard.

[0209] Data Collection

[0210] Reproduction and litter size performance:

[0211] Body weights of individual sows were measured (1) on the day the sow was transferred to the farrowing crate, and (2) at weaning. The data were used to calculate weight loss during lactation using the following formula: Sow BW loss = Weaning - (PRE - (LW + LW / 5.5)), where Weaning = sow weight at weaning; PRE = sow pre-farming weight; LW = litter weight; LW / 5.5 = estimated placental weight (Fahmy, 1971). The number of days in lactation and the number of days from weaning to estrus were recorded. During lactation, sow feed intake was measured by the Gestal Solo system for at least 20 sows / treatment (at least 80 sows were measured). The number of piglets born per litter (live and dead), individual birth weight (live and dead), individual weaning weight, and the number of piglets that died during lactation were recorded. Cross-housing and removal of non-suckling pigs were performed only within the treatment period or to non-experimental littermates within 24 days after birth. No creep feeding was provided during this trial, but sows had unlimited access to feed.

[0212] Statistical analysis

[0213] Data were analyzed using ANOVA with the MIXED procedure of SAS. Sows / litter served as the experimental unit. The statistical model included the fixed effect of dietary treatment and the covariate of litter number. Multiple comparisons between treatments were performed using the Tukey adjustment option of SAS. All results are reported as least squares means. The significance level chosen was α = 0.05. Treatment effects were considered significant if P < 0.05, and values ​​of 0.05 ≤ P ≤ 0.10 were considered statistical trends.

[0214] result

[0215] Birth weight improved linearly in sows fed increasing levels of clay (P < 0.10; Table 8). Preweaning mortality was reduced in sows fed 1 lb / ton compared with sows fed 0.5 lb / ton (P < 0.06). During lactation, feed intake increased in sows fed 1.5 lb / ton of clay (P = 0.06), and total feed intake increased linearly (P < .005) with increasing clay content in the diet.

[0216] Sows fed a diet containing 0.5 lb / ton of clay had a lower (P = 0.02) culling rate compared with control sows. Sows fed a diet containing clay (0.05 < P < 0.10) had a lower rate of broken glass compared with sows fed a diet containing clay (1.0 lb / ton) and lower (P = 0.02) than sows fed a diet containing clay (1.5 lb / ton).

[0217] Example 4: Feeding clay to sows increases litter size at birth and weaning.

[0218] The effect of feeding clay to sows during gestation and lactation was evaluated to determine the effect on reproductive performance. Sows (litter ≥ 2) were randomly selected from a commercial herd and assigned a control diet (CON) or a diet containing 4.0 lb / ton of clay, resulting in 97 sows for CON and 95 sows for clay treatment. Dietary treatments were initiated on day 3 after reproduction and continued through top clay to basal diet until the end of lactation (Tables 8 and 9). Individual sow body weights were measured on the day the sows were transferred to the farrowing crate and at weaning to calculate body weight change during lactation using the following formula: Sow BW change = weaning - (PRE - (LW +LW / 5.5)), where weaning = sow weight at weaning; PRE = sow weight before farrowing; LW = litter weight; LW / 5.5 = estimated placental weight. Lactation length and weaning to estrus interval were recorded. The number of piglets born per litter (live and dead), individual pig birth weight (live and dead), individual pig weaning weight, and the number of piglets that died during lactation were recorded. Cross-housing and starvation were allowed within 2 days after birth and only during the treatment period or for non-experimental littermates. In addition, piglet management, including tail docking, iron injection, and male piglet castration, was performed. Piglets were not restricted from accessing sow feed.

[0219]

[0220]

[0221] Example 4: Effect of feeding clay to pregnant and lactating sows on litter size

[0222] Experimental design, procedures, and data collection

[0223] Animal enclosures

[0224] Sows were housed individually in gestation pens after mating and were fed once a day throughout gestation via feed / water troughs based on their individual body condition scores. Water was available ad libitum. At approximately d 112 of gestation, sows were moved to farrowing pens and randomly placed in farrowing pens. The diet was changed from gestation to lactation diet and was fed ad libitum throughout lactation.

[0225] Diet therapy

[0226] Diet treatment was started approximately 3 days after mating. Every 10 sows located in adjacent stalls were considered as a subgroup. On the first day of the experiment, each subgroup was randomly assigned to one of 4 treatments, wherein topdressing of the product was provided to treatments 2 to 4 (Table 9). A non-test sow was placed between each group to prevent mixing of the experimental diets.

[0227] Table 9. Dietary treatments and assigned colors for sows.

[0228]

[0229] 1 Calculations based on the assumption that average feed intake during gestation is 5.0 lb / day.

[0230] 2 Calculations based on the assumption that average feed intake during lactation is 10.0 lb / day.

[0231] 3 During pregnancy, NQ therapeutic clay mineral was given daily at a ratio of 2.27 g / day + 1:1 containing ground corn (total 4.54 g / day).

[0232] 4 The plant matter was given during gestation at a daily rate of 0.45 g / day + 1:1 ground corn inclusion (total 0.90 g / day).

[0233] Experimental diet

[0234] The basal diet was a standard gestation and lactation diet used by NHF (Table 10A and Table 10B). Treatments 2 to 4 were delivered to sows by topdressing using a specified teaspoon / tablespoon. Topdressing was performed daily during gestation by dripping the product in front of the feed / water trough at a specified rate when feeding in the morning. Air was purged before water delivery.

[0235] Topdress product daily at the lactation-specified rate after farrowing and throughout lactation until weaning. On the day of weaning, return the sows to the gestation barn and monitor the days from weaning to estrus.

[0236] Table 10A. Dietary composition of the basal diet until

[0237]

[0238]

[0239] Table 10B. Dietary composition of the basal diet starting on April 2, 2018.

[0240]

[0241]

[0242] Data Collection

[0243] Reproduction and litter size performance:

[0244] Body weights of individual sows were measured (1) on the day the sow was transferred to the farrowing crate, and (2) at weaning. The data were used to calculate weight loss during lactation using the following formula: Sow BW loss = Weaning - (PRE - (LW + LW / 5.5)), where Weaning = sow weight at weaning; PRE = sow pre-farming weight; LW = litter weight; LW / 5.5 = estimated placental weight (Fahmy, 1971). The number of days in lactation and the number of days from weaning to estrus were recorded. The number of piglets born per litter (live and dead), individual birth weight (live and dead), individual weaning weight, and the number of piglets that died during lactation were recorded. Cross-housing and removal of non-suckling pigs were performed only during the treatment period or to non-experimental littermates within 24 days after birth. Lactation feed intake of a small group of sows was monitored using a Jyga Gestal Solo® electronic sow feeder.

[0245] sample:

[0246] Blood samples were collected from sows before farrowing and at weaning of 25 sows / treatment. The gestation day and lactation period of each sampled sow were recorded. The sow farrowings were balanced into 3 subgroups: P2-4, 5-7, and 8+. Blood samples were collected from 2 piglets (gilts and gilts) at 2 days of age and at weaning and at 25 litters / treatment. The age and individual weight at the time of collection were recorded. Colostrum samples were collected from treatments 1 and 4 (25 sows / treatment) within 24 hours of farrowing. Colostrum samples were not analyzed at this time.

[0247] Statistical analysis

[0248] Data were analyzed using ANOVA with the MIXED procedure of SAS. Sows / litter served as the experimental unit. The statistical model included the fixed effect of dietary treatment and the covariate of litter number. Multiple comparisons between treatments were performed using the Tukey adjustment option of SAS. All results are reported as least squares means. The significance level chosen was α = 0.05. Treatment effects were considered significant if P < 0.05, and values ​​of 0.05 ≤ P ≤ 0.10 were considered statistical trends.

[0249] result

[0250] Sows fed clay had an increase in total pigs born, live born, and heavier birth weights compared to sows fed the control diet (Table 11). The number of pigs born was reduced by less than 1.7 lbs (P < 0.05) for sows fed clay compared to sows fed the control diet. The number of abortions was reduced (P < 0.05) for sows fed clay compared to sows fed the control diet. The increase in total live pigs born for sows fed clay-based diets also resulted in an increase in the number of pigs weaned.

[0251] Table 11. Summary of the 2017-006 Therapeutic Clay x Botanical Long-Term Sow Study

[0252]

[0253]

[0254]

[0255]

[0256] Example 5: Effect of a clay-based diet on farrowing performance in sows

[0257] The sow performance data was analyzed again to determine the response of the sows to feeding clay based on parity (Table 12). The sows were sorted into 6 different parity groups; parity 2, 3, 4 and 5, 6 and 7, and 8 or greater. These data indicate that parity had a major effect on the level of response. 2 parity sows and sows greater than 6 parity had more significant improvements in total births and live pigs born compared to 3, 4, and 5 parity sows, which are typically the parities that tend to result in lower performance due to health issues in 2 parity sows and age / health effects in 6 parity or greater sows. The data indicate that adding clay to the feed actually restored performance to a higher level and improved the overall production of the sow herd.

[0258] Table 12. Effect of farrowing number on sows’ response to clay-based diets throughout gestation + lactation

[0259]

[0260]

[0261] Example 6: Effects on littermate sows

[0262] The data were reanalyzed in Example 6 to determine the effectiveness of feeding a clay-based diet to sows that had more than 15.5 live pigs born (Table 13). These data indicate that live pigs born were increased by 2% and the number of pigs weaned was increased by 0.7 pigs per litter (P = 0.13). These data further indicate that the effect of increasing litter size is not a function of reduced sow performance (>15.5 total pigs born). Even with larger litter sizes, feeding clay in the gestation and lactation diets resulted in more pigs weaned.

[0263] Table 13A. Meta-analysis of high-producing sows fed clay-based diets throughout gestation + lactation

[0264]

[0265] Table 13B. Meta-analysis of high-producing sows fed clay-based diets throughout gestation + lactation

[0266]

[0267] Table 13C. Meta-analysis of high-producing sows fed clay-based diets throughout gestation + lactation

[0268]

[0269] Table 13D. Meta-analysis of high-producing sows fed clay-based diets throughout gestation + lactation

[0270]

[0271] Example 7: Feeding clay to sows increases litter size at birth and weaning

[0272] The effect of feeding clay to sows during gestation and lactation was evaluated to determine the effect on reproductive performance. Sows (parity ≥ 2) were randomly selected from a commercial herd and assigned a control diet (CON) or a diet containing 4.0 lb / ton of clay, resulting in 97 sows for CON and 95 sows for clay treatment. Dietary treatments were initiated on day 3 after breeding and continued through top clay to basal diet until the end of lactation (Tables 14 and 15). Individual sow body weights were measured on the day the sows were transferred to the farrowing crate and at weaning to calculate body weight change during lactation using the following formula: Sow BW change = Weaning - (PRE - (LW + LW / 5.5)), where Weaning = sow weight at weaning; PRE = sow weight before farrowing; LW = litter weight; LW / 5.5 = estimated placental weight. Lactation length and weaning to estrus interval were recorded. The number of piglets born per litter (live and dead), individual pig birth weight (live and dead), individual pig weaning weight, and the number of piglets that died during lactation were recorded. Cross-housing and starvation were allowed within 2 days after birth and only during the treatment period or for non-experimental littermates. In addition, piglet management, including tail docking, iron injection, and male piglet castration, was performed. Piglets were not restricted from accessing sow feed.

[0273] Table 14. Dietary composition of a basic pregnancy diet

[0274]

[0275] 1 Diet updated December 2018 / January 2019.

[0276] Table 15. Dietary composition of the basal lactation diet

[0277]

[0278] 1 Updated on February 22, 2019. Diet.

[0279] Data were analyzed using ANOVA with the MIXED procedure of SAS. Sows / litter served as the experimental unit. The statistical model included the fixed effect of dietary treatment and the covariate of litter number. Multiple comparisons between treatments were performed using the Tukey adjustment option of SAS. All results are reported as least squares means. The significance level chosen was α = 0.05. Treatment effects were considered significant if P < 0.05, and values ​​of 0.05 ≤ P ≤ 0.10 were considered statistical trends.

[0280] The results in Table 16 show that sows fed clay had an increased number of total pigs born (P = 0.15) and live born (P = 0.31) compared to sows fed CON. Litter birth weights were larger in clay-fed sows (P = 0.18) due to larger litter sizes. Pre-weaning mortality was lower in clay-fed sows (P = 0.13) and piglet losses were lower due to low vitality (P = 0.09) compared to sows fed the control. The increase in total live pigs and pre-weaning survival resulted in a greater number of pigs weaned from clay-fed sows (P = 0.08).

[0281] Table 16. Effects of feeding clay to sows during gestation and lactation on reproductive performance

[0282] Comparison clay SE P-value Number of sows 97 95 <![CDATA[Number of litters 1 > 5.7 6.2 0.3 0.24 Pregnancy rate, % 99.2 98.5 N / A 0.95 Fertility rate, % 92.3 89.2 N / A 0.79 Total births 15.1 15.7 0.5 0.15 Birth survival 13.1 13.4 0.4 0.31 Stillbirth, % 8.7 9.6 1.0 0.48 Mummy, % 5.3 5.1 0.8 0.95 Birth weight, lb 36.5 37.8 1.2 0.18 <![CDATA[ Pig birth weight, 2 lb]]> 2.74 2.81 0.06 0.27 Low birth weight (<1.5 lb), % 3.9 3.8 N / A 0.87 Average birth weight (1.5 - 3.0 lb), % 55.3 53.4 N / A 0.51 High birth weight (>3.0 lb), % 40.8 42.8 N / A 0.42 Pre-weaning mortality, % 6.2 4.4 1.2 0.13 Piglet losses due to low vitality, % 2.0 0.8 0.7 0.09 Total weaning 12.2 12.8 0.4 0.08 Length of breastfeeding, days 19.8 19.6 0.3 0.45 <![CDATA[ Pig weaning weight, 3 lb]]> 11.5 11.6 0.2 0.95 <![CDATA[ Litter weaning weight, 3 lb]]> 138.7 145.9 5.7 0.21 Weaning-oestrus interval, days 5.2 4.3 0.5 0.15 Sow BW before farrowing, lb 587 600 6 0.02 <![CDATA[ BW changes of lactating sows, 3,4 lb]]> 5.8 1.1 3.5 0.26 Sow feed intake during lactation Number of sows ADFI during lactation, lb / day 11.1 11.7 0.5 0.62

[0283] 1 Parity was used as a covariate in all analyses.

[0284] 2 Using birth survival as a covariate

[0285] 3 Using lactation length as a covariate

[0286] 4 Using sow BW before farrowing as a covariate

[0287] Example 8: Meta-analysis of three clay sow studies

[0288] Three experiments were conducted following the same procedure to evaluate the effects of feeding clay to sows during gestation and lactation on reproductive performance. In each experiment, sows (farrowing ≥ 2) randomly selected from a commercial herd were assigned a control diet (CON) or a diet containing 4.0 lb / ton of clay, for a total of 294 sows for CON and 302 sows for clay treatment over three experiments. The experimental diets were fed starting on day 3 of gestation and continued until the end of lactation. Data from the three experiments were compiled for meta-analysis using the MIXED procedure of SAS.

[0289] The data in Table 17 show that feeding clay to sows during gestation and lactation increased (P < 0.05) the number of total born, live born, and weaned pigs compared to pigs fed the control diet. As litter size at birth and weaning improved, litter weight at birth and weaning also improved (P < 0.05).

[0290] Table 17. Meta-analysis of three studies on sows fed clay throughout gestation and lactation

[0291]

[0292]

[0293]

[0294]

[0295] Total fecal amino acid concentrations were reduced in clay-fed sows compared to control-fed sows (P < 0.01). In a review by Dai et al. (2015), the prevailing information suggests that amino acid recycling is increased during pregnancy, triggering improved fetal implantation. The regression analysis below suggests that reduced fecal amino acid levels enhance piglet survival after farrowing and weight gain during lactation. Reduced amino acid levels are also indicative of reduced ammonia production, which is beneficial for improved embryonic survival (Dai et al., 2015). Together, these data suggest that improved amino acid utilization or reduced fecal amino acid concentrations are associated with improved signaling to promote pregnancy and reduce fetal exposure to toxins such as ammonia and nitric oxide. Sows fed clay had improved amino acid utilization, further reducing the toxic effects of exposure to high ammonia production. The data in Table 18 further suggest that fecal short-chain fatty acid concentrations were reduced in clay-fed sows. Dai (2015) further suggested that reduced short-chain fatty acids improved insulin sensitivity, which is associated with improved fetal survival and post-weaning development.

[0296] Table 18. Metabolites in sow feces (late gestation)

[0297] project Comparison clay SE P-value %change Number of sows analyzed for fecal metabolites 16 16 Farrowing times 5.75 6.31 0.66 0.55 Reproductive performance of sampled sows Total births 15.2 16.1 0.7 0.34 Birth survival 12.6 13.6 0.7 0.34 Pig birth weight, lb 3.0 3.0 0.1 0.90 PWM, % 8.7 4.9 2.7 0.32 Total weaning 12.2 12.9 0.7 0.53 Pig weaning weight, lb 11.6 12.1 0.5 0.45 <![CDATA[Late pregnancy 1 Metabolites in sow feces]]> Fatty acids in feces, mg / g Acetic acid 4.58 3.28 0.49 0.09 -28% Propionic acid 3.69 2.46 0.45 0.07 -33% Butyric acid 1.99 1.27 0.25 0.07 -36% Valeric acid 0.586 0.375 0.072 0.06 -36% Isovalerate 0.173 0.128 0.020 0.13 -26% Total SCFA 11.00 7.53 1.23 0.07 -32% C6:0 0.019 0.014 0.006 0.54 -26% C8:0 0.0059 0.0056 0.0005 0.67 -5% C14:0 0.125 0.127 0.018 0.93 2% C15:0 0.090 0.178 0.027 0.01 98% C16:0 0.881 1.086 0.075 0.08 23% C16:1 0.017 0.013 0.001 0.08 -22% C18:0 0.336 0.451 0.028 0.009 34% C18:1 0.606 0.723 0.113 0.47 19% Bile acids in feces, ug / g cholic acid 9.52 9.48 0.20 0.88 0% Chenodeoxycholic acid 0.64 0.66 0.13 0.92 3% Lithocholic acid 870 413 104 0.007 -52% Hyodeoxycholic acid 1311 240 178 0.001 -82% Total Bile Acids 2153 719 246 0.001 -67% Amino acids in feces, ug / g Alanine 161 50 17 0.0007 -69% Arginine 26.0 10.0 6.3 <.0001 -61% Asparagine 2.46 1.63 1.14 0.01 -34% Aspartic acid 35.6 47.8 5.5 0.14 34% Citrulline 47.7 37.1 6.1 0.22 -22% Glutamate 564 461 68 0.29 -18% Glutamine 9.87 7.83 0.48 0.01 -21% Glycine 41.0 27.3 8.9 0.07 -33% Histidine 8.41 8.06 0.57 0.67 -4% Leucine / Isoleucine 77.9 22.2 7.6 0.0001 -71% Lysine 85.5 70.4 8.2 0.21 -18% Methionine 23.8 11.8 2.5 0.005 -50% Ornithine 6.40 7.61 1.05 0.43 19% Phenylalanine 92.3 9.3 11.3 0.0001 -90% Proline 41.8 14.7 5.8 0.005 -65% r-Amino-n-butyric acid 5.1 12.3 3.2 0.004 141% Serine 56.5 38.0 4.9 0.02 -33% Taurine 1.83 0.31 0.58 0.08 -83% Threonine 42.9 22.0 3.2 0.0004 -49% Tryptophan 7.9 2.7 1.0 0.002 -65% Tyrosine 73.0 11.7 9.6 0.0005 -84% Valine 77.1 27.5 8.8 0.001 -64% Total amino acids 1490 935 142 0.01 -37%

[0298] Establishment of the prediction equation between PWM and piglet weaning weight by linear regression analysis

[0299] Predict pig weaning weight using the following equation:

[0300] Pig weaning weight (control) = a 2-11 x number of litters (2 – 11) + 1.123 x weaning age - 0.00083 x Total AA in feces of sows at the end of gestation (μg / g) – 0.0215 x Birth weight (lb) – 11.945

[0301] Pig weaning weight (clay) = a 2-11 x number of litters (2 – 11) + 1.123 x weaning age - 0.00201 x Total AA in feces of sows at the end of gestation (μg / g) + 3.342 x Birth weight (lb) – 19.626

[0302] R 2 = 0.82

[0303] The equation indicated that total AA concentration in sow feces collected at the end of gestation was negatively correlated with pig weaning weight in both treatments. Pig weaning weight from sows fed clay had a greater effect from total AA concentration in sow feces of (0.00201-0.00083) / 0.00083 = 142% compared to the control.

[0304] Pre-weaning mortality was predicted using the following equation:

[0305] Pre-weaning mortality (control) = a 2-11 x number of farrowings (2 – 11) + 1.323 x total SCFA – 10.601

[0306] Pre-weaning mortality (clay) = a 2-11 x number of farrowings (2 – 11) + 0.337 x total Total SCFA – 1.463

[0307] R 2 = 0.59

[0308] The equation indicated that total SCFA concentrations in sow feces collected at the end of gestation had a positive correlation with pig PWM in both treatments. Pig PWM from sows fed clay had a smaller effect on total SCFA concentrations in sow feces compared to controls (1.323-0.337) / 1.323 = 75%.

[0309] Example 9: Feeding clay to sows increases total immunoglobulin concentrations in their offspring

[0310] Immunocrit measures the total immunoglobulins in the blood, which are proteins that recognize bacteria and other agents that can cause disease. When piglets are born, they have very small immunoglobulin concentrations (essentially zero). Therefore, all of the immunoglobulins in the blood from newborn piglets come from the sow via colostrum intake. Therefore, Immunocrit measurements can determine if the piglet has received enough colostrum. Previous results have shown that Immunocrit values ​​below 0.05 at birth are associated with a greater risk of pre-weaning mortality due to insufficient colostrum intake. In this experiment, a total of 37 piglets from sows fed a control diet and 50 piglets from sows fed a diet containing clay at 4.0 lb / ton during gestation and lactation were used to evaluate Immunocrit values ​​on day 2 after birth and at weaning.

[0311] The results in Table 19 show that piglets from sows fed clay had 5.9% higher Immunocrit values ​​on day 2 after birth compared to piglets from sows fed the control diet (P = 0.44). Pigs from sows fed clay at birth with < 0.05 Immunocrit were approximately 44% lower than pigs from sows fed the control diet, indicating greater colostrum intake and higher immunoglobulin concentrations. In addition, the greater Immunocrit values ​​in litters from sows fed clay at weaning (7.0% increase) indicate better immune status and potentially better health and growth performance in the later growth period after weaning.

[0312] Table 19. Immunocrit values ​​for piglets obtained from sows fed a control diet and a diet containing clay at 4.0 lb / ton

[0313] project Comparison clay SE P-value % change from control Piglet Immunocrit Number of pigs measured 37 50 Measuring litter size 20 25 Immunocritus on the second day after birth 0.095 0.101 0.005 0.44 + 5.9% % of pigs with Immunocrit < 0.05 10.8 6.0 N / A 0.43 - 44% Immunocrit during weaning 0.040 0.043 0.002 0.25 + 7.0%

[0314] Example 10: Feeding sows with clay improves the survival rate of their offspring from birth to market

[0315] A study was conducted to evaluate the effect of feeding clay to sows during gestation and lactation on the survival of their offspring from birth to market. A total of 352 pigs from sows fed a control diet and 143 pigs from sows fed Clay at 4.0 lb / ton were identified using ear tags and tracked from nursery to market. The clearance rate from nursery to market, as well as the percentage of cleared pigs were lower in pigs from sows fed clay (P = 0.88 and P = 0.06, respectively), resulting in more pigs being sold at the first market compared to pigs from sows fed the control diet (93.0 vs. 88.6%; Table 20). Combining the data shown in Example 1, feeding clay to sows resulted in 0.6 more pigs weaned per litter and 1.1 more pigs marketed per litter due to the higher survival from birth to market compared to pigs fed the control diet.

[0316] Table 20. Survival to birth and market of piglets from sows fed a control diet and a diet containing clay

[0317] .

Claims

1. Use of an effective amount of a therapeutic clay in the preparation of a feed composition for improving the reproductive and litter size performance of a maternal animal, wherein the clay is orally administered to the animal, wherein the animal is a pig, wherein the clay is administered beginning at gestation day 3-93, and wherein the therapeutic clay is K-rectorite, wherein improving reproductive performance comprises improving the immune status of the maternal animal, and wherein improving the immune status of the maternal animal comprises increased levels of IFNγ and TNF-α in the maternal animal, and decreased levels of TRAIL in the maternal animal, wherein the level of TNF-α before farrowing in the maternal animal is positively correlated with total weaning, negatively correlated with subsequent stillbirths, and positively correlated with subsequent mummies, wherein the level of TRAIL before farrowing is negatively correlated with subsequent total births and subsequent birth survival, or wherein the level of IFN-γ during weaning is positively correlated with total weaning.

2. The use according to claim 1, wherein the clay is formulated in a feed composition for oral administration to an animal.

3. The use of claim 1, wherein the clay is administered during pregnancy, during lactation, and combinations thereof.

4. The use of claim 1, wherein improving reproductive performance comprises reducing embryonic loss, increasing litter size, increasing live births, reducing the concentration of maternal fecal amino acids, reducing the concentration of maternal fecal short-chain amino acids, and increasing litter weight.

5. The use of claim 1, wherein improving litter size performance comprises increasing colostrum intake of young animals, reducing pre-weaning mortality of young animals, reducing the number of young animals lost due to low vitality, reducing the number of young animals weaned, improving the immune status of young animals at weaning, reducing the number of young animals with low weight from the nursery to the market, increasing the number of young animals marketed per sow, and increasing calculated litter weight gain.

6. The use according to claim 1, wherein the animal is a pig.

7. The use of claim 6, wherein the amount of clay in the feed composition ranges from about 0.1 lb / ton to 10 lb / ton, the amount of clay in the gestation feed composition ranges from about 0.5 lb / ton to 4.0 lb / ton, the amount of clay in the lactation feed composition ranges from about 0.5 lb / ton to 1.5 lb / ton, the amount of clay administered to the sow ranges from about 1.0 g / d to about 10 g / d, the amount of clay administered to the animal ranges from about 0.1 g / d to about 8 g / d, the amount of clay administered to the animal during gestation ranges from about 0.5 g / d to about 3 g / d, or the amount of clay administered to the animal during lactation ranges from about 4.0 g / d to about 7 g / d.

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