CN1988888A - Encapsulated transfer factor compositions and methods of use - Google Patents

Abstract

Compositions comprising transfer factor and/or dextran, such as hybrid dextran, coated with a hydrophobic or lipid coating. The composition may be combined with nutraceuticals including zinc, essential fatty acids, lactic acid producing bacteria, and the like. Methods of using these compositions for the prevention and treatment of pathological conditions in animals and methods of making these compositions are also provided.

Description

Encapsulated transfer factor compositions and methods of use

field of invention

The present invention relates to encapsulated compositions comprising: (1) transfer factor coated with a hydrophobic or lipid coating and/or (2) dextran coated with a hydrophobic or lipid coating, such as fungal dextran sugar or hybrid dextran. Such compositions are useful in the prophylaxis and treatment of pathological conditions.

Background of the invention

Transfer factors, produced by leukocytes and lymphocytes, are small water-soluble polypeptides of approximately 44 amino acids that stimulate or transfer cell-mediated immunity from one individual to another and across species, but do not produce allergic reactions. Since transfer factors are smaller than antibodies, they do not transfer antibody-mediated responses and do not induce antibody production. The properties, characteristics and methods of obtaining transfer factor are described in US Pat.

Transfer factor has been described as an effective treatment for herpes simplex virus (Viza et al.); in the treatment of acne blemishes (US Pat. No. 4,435,384) and as a treatment for Candida albicans (Khan et al.). Transfer factor is also used in the treatment of intestinal cryptosporidiosis in recipients treated with specific transfer factor (McMeeking et al.). Still et al. also demonstrated prevention of varicella infection by pre-treating children with transfer factor from individuals who had had varicella, or in other words had been sensitized to varicella antigens. Antigen-specific transfer factors are the most well-studied and it has been demonstrated that they are capable of imparting the antigen recognition capacity of experienced donors to naive recipients. The individual or animal that can be presumed to be the source of the transfer factor has been sensitized to the antigen of interest. The term antigen is defined herein as any substance that elicits a cell-mediated immune response. However, transfer factors as found in commercial bovine colostrum extracts derived from animal groups such as cattle contain acquired immunity from all populations and thus provide systemic adoptive transfer of a class of immunity. One or more transfer factors may be obtained from a dialyzable extract of lysed cells or from an extract of extracellular fluid containing transfer factor. Common sources of transfer factor are colostrum and eggs. It is common practice to refer to formulations that contain transfer factor as the active ingredient (ie transfer factor or TF). A transfer factor extract containing transfer factor is also referred to herein as transfer factor. Transfer factor from bovine colostrum extract was defined as the defatted water-soluble material from colostrum that passed through a nominal 10,000 molecular weight filter. Colostrum-derived transfer factors were prepared that were active against various organisms, including bovine nasal infectious tracheitis virus. One of the specific effects of transfer factor is a marked increase in natural killer (NK) cell activity. Natural killer cells provide defense against viruses as part of the innate immune defense system.

Although transfer factor is a polypeptide, it is reported to be surprisingly stable in the gastrointestinal tract. For example, Kirkpatrick compared oral versus parenteral administration of transfer factor in a clinical study. Kirkpatrick, Biotherapy, 9:13-16, 1996. He concluded that the results disproved any argument that the acidic or enzymatic environment of the GI tract might hamper oral therapy with transfer factor.

When attempting to sequence TF, the N-terminus of the transfer factor peptide was reported to be resistant to sequential Edman degradation. Kirkpatrick, Molecular Medicine, 6(4):332-341 (2000).

Transfer factors have also been successfully used in the treatment of animal diseases and syndromes including compositions in ruminants. See US Patent Publication No. US2003/0077254, published April 24, 2003.

Therefore, transfer factor is believed to be stable in the gastrointestinal tract and rumen.

Summary of the invention

The present invention is based on the discovery that transfer factor is not as stable as once thought. This is especially true in the case of ruminants.

The present invention provides compositions wherein transfer factor and/or glucan are "encapsulated". Encapsulation protects transfer factor and/or dextran from inactivation in the gastrointestinal tract. Such cysts are especially important in ruminants where digestion in the rumen is found to be a problem. Bioavailability has been demonstrated to be enhanced when transfer factor is encapsulated and administered to ruminants. In a preferred embodiment, a coating is formed around the transfer factor and/or dextran by encapsulating the transfer factor and/or dextran by mixing with a hydrophobic substance or lipid.

Encapsulated formulations containing encapsulated transfer factor and/or encapsulated dextran may be combined with minerals, antioxidants, amino acids and other nutraceuticals. As used herein, "encapsulated formulation" refers to an encapsulated transfer factor formulation and/or an encapsulated dextran formulation. Thus, an encapsulated formulation may refer to an encapsulated transfer factor formulation, an encapsulated dextran formulation, or an encapsulated formulation containing both encapsulated transfer factor and encapsulated dextran.

One aspect of the invention resides in prophylactically administering an encapsulated formulation to an animal.

Another aspect resides in the administration of encapsulated formulations to animals for the treatment of pathological conditions such as heart disease, inflammation and vascular disease.

Another aspect resides in administering the encapsulated formulation to an animal to increase food conversion.

Another aspect resides in the provision of transfer factor formulations, such as encapsulated formulations comprising one or more targeted transfer factors.

Another aspect of the present invention is to provide a transfer factor preparation, wherein the transfer factor includes a targeted transfer factor, eg, targeted to Herpes Simplex Virus 1, Herpes Simplex Virus 2, Helicobacter pylori, Champhobactor or Chlamydia.

Another aspect of the present invention is to provide an encapsulated formulation further comprising lactic acid bacteria.

Another aspect of the present invention is to provide an encapsulated formulation further comprising phytic acid, olive leaf extract, aloe extract powder and β-sitosterol.

Another aspect of the present invention is to provide an encapsulated formulation further comprising yeast extract.

Another aspect of the present invention is to provide an encapsulated formulation further comprising ascorbic acid.

Another aspect of the present invention is to provide an encapsulated formulation further comprising dibasic potassium phosphate.

Another aspect of the present invention is to provide an encapsulated formulation further comprising potassium chloride, magnesium sulfate and calcium pantothenate.

Another aspect of the present invention is to provide an encapsulated formulation further comprising vitamin E.

Another aspect of the present invention is to provide encapsulated formulations further comprising vitamin C, vitamin A, vitamin D3, vitamin B1, vitamin B2 and vitamin B12.

Another aspect of the present invention is to provide formulations further comprising encapsulation of zinc, such as zinc proteinate.

Another aspect of the present invention is to provide a transfer factor formulation wherein rumen shunting is achieved by injecting said formulation into an animal, for example by intravenous, intramuscular or subcutaneous injection.

Another aspect of the present invention is to provide transfer factor formulations wherein rumen shunting is achieved by administering the formulations to the animal intravaginally, intranasally, intrarectally, directly on the mucosa or by inducing opening of the esophageal groove.

Another aspect of the present invention is to provide a method of preparing the encapsulated formulation described herein by combining the various components into said formulation.

Another aspect is to provide a method of making hybrid glucans by contacting two different fungi in culture with a composition such as a fungal cell wall degrading snake venom. This allows genetic exchange between two fungi that provide hybrid fungal preparations for making hybrid glucans and other hybrid compositions.

Also disclosed are hybrid fungi produced by this method, as well as hybrid glucans and other hybrid molecules found in such hybrid fungi.

Brief description of the drawings

Figure 1 presents the results obtained using the encapsulated transfer factor formulations of Table 7. When animals treated with encapsulated transfer factor were compared to controls not treated with transfer factor, morbidity decreased from 15.5% to 3.1%, while mortality decreased from 5.5% to 0%. In addition, the daily weight gain of the control group was 1.85 lbs/day compared to 3.05 lbs/day for those animals treated with the encapsulated transfer factor formulation.

Figure 2 is a second study involving the use of the encapsulated transfer factor formulations of Table 7 in a different field study using highly stressed cattle. In the present study, animal morbidity decreased from 83% to 2.6%, while mortality decreased from 24% to 0 in those animals treated with the encapsulated transfer factor preparation compared to the control group that did not receive transfer factor %. Additionally, the control population had a body weight gain of 0.9 lbs/day compared to 3.1 lbs/day for those animals treated with the encapsulated transfer factor formulation.

Detailed description of the invention

The encapsulated formulations of the invention contain encapsulated transfer factor and/or encapsulated dextran, including hybrid dextrans. Transfer factor and/or dextran may each be encapsulated separately or as a mixture. Alternatively, the monolithic formulation can be encapsulated.

Various forms of transfer factor can be used in the present invention. They include secreted transfer factors released from transfer factor-containing cells such as lymphocytes, leukocytes and eggs and collected from extracellular fluids such as colostrum and blood. Another form involves pre-secreted transfer factor found inside or on the cell surface. Substantially purified transfer factor derived from leukocytes, colostrum or eggs and having a molecular weight below 10,000 Daltons and a specific activity at 214 nm of at least 5000 units/absorbance unit may also be used. The transfer factors used in the examples of the present invention and referred to in the table below and further referred to in the remainder of the detailed description were extracted from colostrum and eggs collected from a general pool of lactating cows. Transfer factor as used in the Examples, Tables, and description below is further defined as the defatted water-soluble material from bovine colostrum passed through a nominal 10,000 molecular weight filter. Although bovine colostrum-derived transfer factor was used to develop the formulations of the present invention, it is well known to anyone skilled in the art that other types and sources of transfer factor can be used.

Alternative sources of transfer factor include, but are not limited to, avian transfer factor, egg transfer factor, and transfer factor isolated from colostrum collected from non-bovine animals such as goats, pigs, horses, and humans. Furthermore, combinations of transfer factors from any number of sources may be used in the formulations of the invention. Transfer factors can also be derived from recombinant cells genetically engineered to express one or more transfer factors or by clonal expansion of leukocytes.

Alternative classes of transfer factors include, but are not limited to, targeted transfer factors. Targeted transfer factors include transfer factors collected from sources that have been exposed to (1) one or more viruses, or other infectious organisms; (2) one or more antigens that generate an immune response; or (3 ) combination of organism and antigen. Examples of such viruses or other infectious organisms include herpes simplex virus 1, herpes simplex virus 2, Helicobacter pylori, Champhobactor and Chlamydia, bovine rhinotracheitis virus, parainfluenza, respiratory syncytial virus vaccines, modified Live virus, Campylobacter fetalis, Leptospira canis, Typhoid type, Harjo type, Leterohaemorrhagiae, Leptospira Pomona type vaccine, Bovine rotavirus-coronavirus, Escherichia coli vaccine, Shore Clostridium, Gangrene Antitoxin, Acinetobacter haemolytica, Novy, Sordellii, Clostridium perfringens types C&D, Bacterin, Toxoid, Haemophilus somnus, Pasteurella haemolytica, Multocida bacterin. However, those skilled in the art will readily recognize a variety of other viruses and other infectious organisms that find application in the present invention. Examples include those listed in Appendix I and Appendix II.

Typical compositions of montmorillonites are listed in Table 1.

Tables 2-6 list transfer factor formulations that have been used to treat various animals and pathological conditions. In each case, transfer factor was not encapsulated as described herein. However, transfer factor is readily encapsulated in each of these formulations using a hydrophobic or lipid coating and thereafter mixed with the other ingredients in the formulation.

Table 2 presents a breakdown of the formulation of transfer factor nutraceuticals and carriers for the treatment of Cushing's syndrome, Cushing's disease, adenoma, onchocerciasis, hypothyroidism or EPM. References in Table 2 and all other tables to "lb" (pounds) refer to body weight in pounds.

The approximate high, low and preferred amounts of formulation ingredients to be administered to animals in a single dose are shown in columns 2, 3 and 4 of Tables 2-6, respectively, in amounts/body weight. The formulations in Tables 3 and 4 are very similar to those in Table 2, but they are specific for dogs and cats, respectively. The formulations represented in Table 2 were primarily designed for livestock use. The 5 oz formulation listed in column 5 was designed to be given to a 1000 lb animal, but could be varied and in some cases could be given to a 500 lb animal. The average horse weighs about 1000 pounds. The 28.3 gm dose in Table 3 is calculated for a dog weighing approximately 100-200 lbs, but this dose could also be given to a 15 lb dog. The 2.2 gm formula in Table 4 is for cats weighing approximately 15 lbs. However, since these formulations consist of nutraceuticals and transfer factors, those skilled in the art will recognize that this range is not definitive and not as critical as the range of allopathic drugs.

In addition, the formulations in Tables 2-4 were designed primarily for chronic diseases, the formulations in Table 5 were designed primarily for acute diseases, and the formulations in Table 6 were designed for both acute and chronic diseases. All formulations can be administered in bolus doses to achieve an acute response.

Table 7 provides encapsulated transfer factor formulations for use in the treatment of pathological conditions. The transfer factor preparation comprises at least encapsulated transfer factor derived from bovine and avian sources and/or one or more hybrid glucans. Preferably the dextran moiety in the formulation is also encapsulated. Other ingredients include zinc protein, targeted avian transfer factor, beta-sitosterol, phytate (IP6), olive leaf extract, aloe extract powder, probiotics, Bacillus subtilis, Bifidobacterium longum, Thermobacillus, Lactobacillus acidophilus, Enterococcus faecalis and Saccharomyces cerevisiae. In a preferred embodiment, the transfer factor formulation includes all of the above ingredients.

In preferred encapsulated embodiments, transfer factor is present in the formulation in an amount of 10 mg-12 gm/oz, more preferably 100 mg-6 gm/oz, and most preferably 10 mg-3 gm/oz.

Transfer factor is encapsulated with a hydrophobic or lipid coating preferably at 25%-150 wt/%, about 50-150 wt/% and about 75-125 wt/% of transfer factor, most preferably equal weight.

In a preferred embodiment, the hybrid glucans used in the present invention are present in or derived from Cordyceps genus and in particular Cordyceps hybrids. One technique for inducing Cordyceps hybridization involves plating two different strains or species onto a single agar plate that has been inoculated with rattlesnake venom, as detailed in Examples 17 and 18. As stated, the venom acts to weaken the cell wall of the Cordyceps strains/species, which allows nucleoplasmic exchange between the strains/species as they grow close to each other. In a preferred embodiment, the hybrid strain producing the hybrid glucans of the invention is Cordyceps Alohaensis obtained from Pacific Myco Products, Santa Cruz, California.

Many different strains of Cordyceps exist, and many taxonomists consider them distinct species because of their variable form of asexual mycelial growth. A non-exhaustive list of strains includes: Paecilomyces hepiali Chen, Cephalsporim sinensis, Paecilomycessinensis Cn80-2, Scydalilum sp., Hirstutella sinenis, Mortierella hepiali, Chen Lu, Topycladium sinensis, Scytalidium hepiali, G.L.Li. Preferred embodiments of the invention utilize hybrid glucans from hybrids of one or more of these different strains, however, the invention may alternatively preferentially include glucans from non-hybrid strains. An alternative embodiment uses a full hybrid Cordyceps, eg Cordyceps Alohaensis. Hybrid glucans also include those obtained by hybridizing feed sources such as oats and the like.

When dextrans or hybrid dextrans are used, the formulation preferably contains 10 mg-18 gm whole organism/oz, more preferably 100 mg-10 gm whole organism/oz and most preferably 100 mg-5 gm whole organism/oz.

It is also possible to use equivalent amounts of purified or partially purified dextran or hybrid glucans and related nucleosides (such as cordycepin (3' deoxyadenosine), adenosine and N ⁶ -(2 hydroxyethyl)-adenosine).

For encapsulated transfer factor, the preferred amount of hydrophobic or lipid coating is about 25%-150wt/%, about 50-150wt% or about 75-125wt/% of the hybrid dextran, most preferably equal weight.

Other ingredients in the formulation may also be encapsulated. For example, IP6, beta-sitosterol, olive leaf extract, aloe extract and/or vitamin C can be encapsulated separately or they can be combined with one or more ingredients, followed by encapsulation. In preferred embodiments, IP6 is present in an amount from 10 mg to 3 gm/oz, or in a preferred case from 100 mg to 2 gm/oz, and most preferably from 100 mg to 1 gm/oz. The preferred amount of beta-sitosterol is 10 mg-3 gm/oz, or preferably 100 mg-2 gm/oz, and most preferably 100 mg-1 gm/oz. Olive leaf extract is preferably present in an amount from 2 mg to 2 gm/oz, more preferably from 5 mg to 1 gm/oz, and most preferably from 5 mg to 500 gm/oz. Aloe extract is preferably present in an amount of 2 mg-1000 mg, more preferably 5-500 mg/oz, and most preferably 5-250 mg/oz. Vitamin C may be present in an amount from 10 mg/oz to 10 gm/oz, or preferably from 100 mg to 8 gm/oz, and most preferably from 100 mg to 5 gm/oz.

The amount of transfer factor and/or dextran used in the formulation or administered varies according to the severity of the clinical manifestations presented. In addition, the amount of transfer factor administered to a recipient varies with the species from which the transfer factor is derived as compared to the recipient species. It has been observed that administration of transfer factor derived from a bovine species to cattle is more effective than transfer factor from another species such as birds. Therefore, when the source and recipient of transfer factor are of different species, it is preferable to increase the amount of transfer factor.

Administration of encapsulated transfer factor with zinc and at least one essential fatty acid is expected to be at least partially effective in producing Cushing's syndrome, Cushing's disease, adenomas and other benign neoplasms, onchocerciasis, hypothyroidism, or EPM Treatment. This treatment was even more effective when the other nutritional products listed in Table 2 were added. Doses are in mg/lb unless otherwise indicated. The ingredients are present in the amounts shown in Table 2, column 5, in 5 ounces of transfer factor formulations with other preferred nutritional products.

Dose of approximately 0.75 mg/lb once daily in animals with Cushing's syndrome, Cushing's disease, adenoma or other benign tumors, onchocerciasis, hypothyroidism, or equine protozoan myelitis (myelytis) Encapsulated transfer factor combined with approximately 0.49 mg/lb zinc and 20.57 mg/lb canola oil, safflower oil or linseed oil as a source of essential fatty acids (i.e. 3,6,9 omega fatty acids) should reduce the size and /or about 30%-50% reduction in symptoms of these listed diseases. All of these ingredients should, of course, be pharmaceutically acceptable to the animal receiving them.

Vitamin C at about 2.16 mg/lb and yeast at 2.29 mg/lb in combination with transfer factor and other fatty acid nutraceuticals described above should reduce the size of benign tumors and/or symptoms of the diseases described above by about 40%-50%.

In all formulations of the invention, it is preferred to proteinate the metal nutraceuticals because these forms are easier for the animal to digest and also because the proteinate form is more stable to pH. The nutritional ingredients in the formulations in Tables 2-7 are the active ingredients used in the treatment of various diseases and syndromes described. Fillers and carriers are included to make the formulation more palatable to the animal and also help preserve the mixture. They include silicon dioxide, maltodextrin, soy and peanut flours, peanut oil, dextrose, whey, flavorings and flavorings. Mixed tocopherols and choline chloride are nutraceuticals, but the potent effects described herein can still be obtained by deleting these two ingredients from the formulation.

Previous use of non-encapsulated transfer factor in ruminants such as cattle produced significant beneficial effects. See, for example, US Patent Publication No. US2003/0077254, published April 24, 2003, which is incorporated herein by reference in its entirety. Oral administration of transfer factor was subsequently found to be unstable in stressed cattle. After the discovery that transfer factor was inactivated in vitro in the presence of rumen fluid and bacterial flora, it was determined that previous success with transfer factor in ruminants was due to the presence of an esophageal groove. When not stressed, the esophageal groove provides partial shunt of the rumen. However, in stressed populations, the esophageal groove closes and shunts transfer factor preparations into the rumen. Formulations encapsulated with hydrophobic substances or lipids encapsulating transfer factor and/or dextran were found to be sufficient to provide substantial shunting of the rumen (eg 85%) even in stressed populations.

Various other methods are known for rumen shunting. In one embodiment, the encapsulated or unencapsulated formulation is injected directly (subcutaneously, intramuscularly or intravenously), thereby bypassing not only the rumen but the entire digestive system. Similarly, intravaginal, rectal or other direct administration to the mucosa, such as the subconjunctiva, bypasses the digestive system and particularly the rumen. Alternatively, the formulation can be mixed with various solvents that allow direct skin absorption. Furthermore, methods of stimulating the opening of the esophageal groove in various ruminants are known in the art, and such opening enables immediate passage of orally administered formulations to the gastrointestinal tract, thereby bypassing the rumen.

In particularly preferred embodiments, rumen shunting is facilitated through the use of encapsulated transfer factor formulations.

The encapsulated transfer factor and/or encapsulated dextran preparations can be produced in various ways. In a preferred embodiment, each of transfer factor and/or dextran in an encapsulated formulation as described in U.S. Patent No. 5,190,775, U.S. Pat. The contents are incorporated herein by reference. Briefly, the approaches described in the cited patents and applications focus on the application of a hydrophobic or lipid coating that provides protection from the degradative properties of the rumen, combined with an additional surfactant coating that inhibits floating of the encapsulated formulation, In order to facilitate the preparation to leave the rumen and pass further through the digestive system. Preferred examples of hydrophobic coatings include, but are not limited to, vegetable oils and hydrogenated vegetable oils, each derived from or made from palm, palm kernel, cottonseed, soybean, corn, peanut, babassu, sunflower or safflower oils and mixtures thereof . Additionally, such coatings may be mixed with waxes such as, but not limited to, beeswax, petroleum wax, rice wax, castor wax, microcrystalline wax, and mixtures thereof. Preferred examples of surfactants include, but are not limited to, polysorbate 60, polysorbate 80, propylene glycol, sodium dioctyl succinyl sulfonate, sodium lauryl sulfate, lactic acid esters of fatty acids, Polyglycerides and mixtures thereof.

Such encapsulated preparations have several benefits beyond their role in rumen shunting. First, encapsulation prevents degradation of the formulation and provides a significantly longer shelf life. Such encapsulated formulations can withstand heating to temperatures above 135[deg.]F, which is required in many production processes including pelleting animal feed or processing human consumables. Encapsulation also removes the bitterness and odor normally present in formulations and thereby greatly increases palatability. Encapsulation also imparts flexibility in the formulation so that fragile ingredients do not interact with harsh minerals, salts or variable pH.

Encapsulated formulations such as encapsulated transfer factor formulations are preferred for human and animal consumption due to increased shelf life, heat stability, palatability and flexibility. Preferred embodiments for human consumption include, but are not limited to, incorporation of encapsulated transfer factor formulations in processed foods such as cereals, snacks, potato chips or bars. Preferred embodiments for animal consumption include, but are not limited to, encapsulated transfer factor formulations mixed into feed pellets, lick salt, lick molasses, or other processed feed products.

Encapsulated transfer factor preparations should be used to increase food conversion efficiency. Food conversion efficiency is the rate at which an organism can convert food into body weight, and is also referred to in the cattle industry as feed conversion efficiency. Encapsulated transfer factor preparations have been used successfully to gain body weight in cattle at an increased rate compared to untreated cattle, even in cases of disease in treated cattle. Thus, encapsulated preparations are not limited to the prophylaxis and treatment of pathological conditions, but also have application in other aspects of the general health and development of an organism.

The encapsulated transfer factor formulations of the present invention include pharmaceutical compositions suitable for administration. In preferred embodiments, the pharmaceutical compositions are in water-soluble form, such as present as pharmaceutically acceptable salts, which is meant to include acid and base addition salts. "Pharmaceutically acceptable acid addition salts" means those salts that retain the biological availability of the free base and are not biologically or otherwise undesirable, formed with inorganic and organic acids, such as hydrochloric acid , hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, etc., and organic acids such as acetic acid, propionic acid, glycolic acid, pyruvic acid, oxalic acid, maleic acid, malonic acid, succinic acid, fumaric acid, tartaric acid, citric acid, benzene Formic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, salicylic acid, etc. "Pharmaceutically acceptable base addition salts" include those derived from inorganic bases, such as sodium, potassium, lithium, ammonium, calcium, magnesium, iron, zinc, copper, manganese, aluminum salts, and the like. Ammonium, potassium, sodium, calcium and magnesium salts are particularly preferred. Salts derived from pharmaceutically acceptable organic non-toxic bases include salts of primary, secondary, and tertiary amines, substituted amines, including naturally occurring substituted amines, cyclic amines, and base ion exchange resins. , such as isopropylamine, trimethylamine, diethylamine, triethylamine, tripropylamine and ethanolamine.

Pharmaceutical compositions may also include one or more of the following: carrier proteins, such as serum albumin; buffers, such as sodium acetate; fillers, such as microcrystalline cellulose, lactose, corn, and other starches; binders; Sweeteners and other flavoring agents; coloring agents; and polyethylene glycols. Additives are well known in the art and are used in various formulations.

In another embodiment, the pharmaceutical composition is incorporated into micellar formulations; see US Pat. No. 5,833,948, which is incorporated herein by reference in its entirety.

Combinations of pharmaceutical compositions can be administered. In addition, the compositions can be administered in combination with other therapeutic agents.

A daily dose of 141 mg/lb body weight of any of the formulations in column 5 of Tables 2, 3 or 4 for 14 days has successfully treated feline pneumonia, feline leukemia, feline autoimmune dysfunction, feline flea bite dermatitis, Feline hyperthyroidism, feline viral infection, feline ulceration, feline bacterial infection, canine flea bite dermatitis, canine Cushing's disease, malignancy, canine autoimmune dysfunction, canine viral and bacterial infection. Most of these treatments have resulted in complete cures. The use of encapsulated transfer factor in these formulations is expected to yield equal or better results.

Administration of formulations including preferred doses of all nutritional products in Table 2 to animals with benign tumors resulted in a reduction in the size of the benign tumors by about 60% and a reduction in the symptoms exhibited by animals with the above-mentioned diseases and syndromes by about 90%. %. The use of encapsulated transfer factor in these formulations is expected to yield equal or better results.

Administration of all nutritional products in Table 2 at low doses in column 3 of those Tables reduced tumor size by about 7%-100% and reduced symptoms exhibited by animals with those diseases or syndromes by 30%- 100%. The use of encapsulated transfer factor in these formulations is expected to yield equal or better results.

The stress formulations in Table 5 are also used in the treatment of numerous animal diseases and syndromes and, as previously mentioned, are mainly used in their acute phase. This formulation is also water soluble and thus can be administered in the drinking water of animals. Twice daily administration of a mixture of approximately 0.75 mg/lb transfer factor and approximately 1.42 mg/lb Lactobacillus acidophilus ¹⁰⁹ colony forming units (CFU) resulted in clinical symptoms due to glandular plague, dust cough, hypothyroidism, and lymphopenia Reduce by at least 30%. Giving the same dose to young cattle also reduced the incidence by about 30%. Addition of twice-daily ionic salts or chelates of calcium, magnesium, sodium and potassium to the above-mentioned amounts of transfer factor and lactic acid-producing bacteria in amounts approximately those in column 4 of Table 5 resulted in a 40% reduction in the clinical symptoms of the above-mentioned diseases. %. Addition of about 0.482 mg/lb of citric acid to the above formulation resulted in about a 45% reduction in the symptoms of the above disease. Further addition of vitamins A, _B2 , _B6 , _B12 , C and E and thiamine resulted in a 50% reduction in the symptoms of these diseases. Administration of the stress preparation once or twice daily in the doses indicated in column 4 of Table 5 will cure or at least treat and alleviate autoimmune dust cough, diarrhea due to viral etiology, abscesses, plague, infestation Runny nose, acute viremia in pigs, grape boils in horses, hypersensitivity reactions due to grape boils and onchocerciasis, PURRS, BRD, calf dysentery, coliform infections, Rhodococcus infections, Symptoms of Clostridium infection, circovirus in birds and pneumonia in cats. The combination of transfer factor and lactic acid producing bacteria or further combining this combination with yeast as shown in Table 5 can also treat these diseases, but to a lesser extent. Application of encapsulated transfer factor is expected to yield equal or better results.

Administration of stress formulations as shown in Table 5 once or twice daily also improved body weight gain and feed efficiency of livestock. Weight gain can be improved by at least 8%. The combination of transfer factor and lactic acid producing bacteria or combining this combination further with yeast as shown in Table 5 also improved body weight gain, but to a lesser extent. Application of encapsulated transfer factor is expected to yield equal or better results. In a preferred embodiment, 2 gm of encapsulated hybrid dextran containing 1 gm of hybrid dextran is used.

A breakdown of the performance formulations of transfer factor and nutraceuticals for the treatment and cure of numerous diseases such as arthritis, laminitis, inflammation and malignancy is shown in Table 6. The following combinations can also be used to treat these diseases: transfer factor and superoxide dismutase; transfer factor and glucosamine salt; transfer factor, glucosamine salt and superoxide dismutase; transfer factor, glucosamine salt, superoxide dismutase and glycine; transfer factor, glucosamine salts, superoxide dismutase, glycine, and dimethylsulfone; transfer factor, glucosamine salts, superoxide dismutase, glycine, dimethylsulfone, and octocosonol; or transfer factor, glucosamine salt, superoxide dismutase, glycine, dimethyl sulfone, octocosonol and montmorillonite.

Table 7 shows formulations containing transfer factor with hybrid and non-hybrid dextran.

Any of the above formulations may be incorporated into the encapsulated formulation.

Table 1

Montmorillonite composition

Average Nutrient Content Per Ounce

(1 tablespoon = ~0.36oz.)

(mg)

Silicon 6933 Tungsten 0.218

Aluminum Silica 2505 Vanadium 0.215

Sodium chloride 1320 Ruthenium 0.210

Potassium 1293 Baron 0.189

Protein 1116 Bromine 0.140

Calcium 1104 Cobalt 0.129

Sulfur 431 Selenium 0.110

Iron 431 Syprosium 0.107

Magnesium 224 Fluorine 0.102

Chlorine 164 Scandium 0.0997

Titanium 61.9 Samarium 0.0943

Carbon 48.2 Nucleus 0.0754

Sodium 37.2 Copper 0.0593

Barium 10.5 Praseodymium 0.0539

Phosphate 8.62 Erbium 0.0539

Strontium 6.46 Hafnium 0.0539

Cesium 4.93 Ytterbium 0.0377

Manganese 4.04 Lithium 0.0377

Thorium 2.69 Yttrium 0.0323

Uranium 2.69 Holmium 0.0296

Arsenic 1.97 Cadmium 0.0296

Chromium 1.89 Palladium 0.0189

Molybdenum 1.64 Terbium 0.0161

Nickel 1.62 Thulium 0.0161

Iodine 1.28 Gold 0.0161

Lead 1.17 Tantalum 0.0135

Cerium 1.08 Iridium 0.0135

Rubidium 0.983 Lutetium 0.0108

Antimony 0.781 Europium 0.0108

Gallium 0.673 Rhodium 0.0108

Germanium 0.673 Tin 0.0108

Neodymium 0.539 Silver 0.00808

Zinc 0.539 Indium 0.00808

Lanthanum 0.486 Oxygen 0.00539

Bismuth 0.385 Mercury 0.00269

Zirconium 0.269 Tellurium 0.00269

Rhenium 0.269 Beryllium 0.00269

Thallium 0.269

Table 2

premix formulation

(Amounts in mg/lb body weight unless otherwise stated)

Element high Low Preferred Dosage: mg/5oz. Formula 1-Arginine*Lacto Yeast (4.9% blend) Montmorillonite Canola Oil (14.5% blend) Safflower Oil (14.5% blend) Linseed Oil (55% Alpha Linolenic Acid) (1.0% Blend) Phosphorus (Phosphoric Acid Sodium Dihydrogen) 12% Calcium Carbonate 8.5% (38% Calcium) Dimethylsulfone Transfer Factor Vitamin C (Ascorbic Acid) D-Biotin (Vitamin H2%) Vitamin D ₃ Vitamin B ₁₂ Folic Acid Niacinimide Pantothenic Acid (d-Calcium Pantothenate) 91.6 %Vitamin B ₆ (Hcl pyridine) 82.3%) Vitamin A (Vitamin A Palmitate) 650M IU/g Feed Grade Vitamin B ₂ Thiamine (Mononitrate) 83% Vitamin E Vitamin K Cobalt (Protein) 5% Copper ( Proteinate) 10% Iodine (Potassium Iodide) 98% Iron (Proteinate) 15% Magnesium (Oxide) 58% Manganese (Proteinate) 15% Molybdenum (Sodium Molybdate Dihydrate) 39% Selenium (Sodium Selenite) 44.8% Zinc (Proteinate) 15% 1-Lysine (-HCl) d, 1-Methionine Mixed Tocopherols Choline Chloride Sipernat 50 (Silicon Dioxide) Lodex-5 (Maltodextrin) Soy Powder (17.5% Blend) Sweet Whey BF70 Spice Dextrose Powder  0.569.511gm/lb1.5gm/lb1.5gm/lb1.5gm/lb15.750gm13.68gm2050.0021.629.7329.16IU0.0921120.3241.158600IU0.05543.0972.9IU10.000430.560.0053.31101.650.050.00162508.4111.03   0.0050.69510.241182.052.052.050.05250.04850.020.050.21620.0009730.7298IU0.0000920.0010060.0121570.01080.0011584.02IU0.0027760.003080.0729IU0.00070.0000430.01120.0000530.03310.040.040.0010.0000810.049870.08410.1103     0.056.912.411820.57120.5720.5715.084.8820.752.1620.009737.298IU0.000920.010060.121570.1080.0115840.212IU0.027760.03080.729IU0.0070.000430.1120.000530.3310.40.40.010.000810.49870.8411.103     50.006951.882411.8820571.8820571.881418.755080.004880.002000.00750.002162.5010.007298.38IU0.9210.06121.57108.0011.5840232.50IU27.7630.80729.42IU7.000.43112.000.53331.16400.00332.1010.001.00498.72841.571103.86300.002434.0012768.757519.3824828.13996.00146.00750.00

(*) Lactic acid producing bacteria make up two thirds of the ingredient and yeast one third; lactic acid producing bacteria 500,000,000 CFU/gm, yeast (eg "Saccharomyces") 250,000,000 CFU/gm

table 3

Canine Premix Formulation

(Amounts in mg/lb body weight unless otherwise stated)

Element high Low Preferred Dosage: mg/oz formulation 1-Arginine*Lacto Yeast (4.9% blend) Montmorillonite Canola Oil (14.5% blend) Safflower Oil (14.5% blend) Linseed Oil (55% Alpha Linolenic Acid) (1.0% Blend) Phosphorus (Phosphoric Acid Sodium Dihydrogen) 12% Calcium Carbonate 8.5% (38% Calcium) Dimethylsulfone Transfer Factor Vitamin C (Ascorbic Acid) D-Biotin (Vitamin H2%) Vitamin D ₃ Vitamin B ₁₂ Folic Acid Niacinimide Pantothenic Acid (d-Calcium Pantothenate) 91.6 %Vitamin B ₆ (Hcl pyridine) 82.3%) Vitamin A (Vitamin A Palmitate) 650M IU/g Feed Grade Vitamin B ₂ Thiamine (Mononitrate) 83% Vitamin E Vitamin K Cobalt (Protein) 5% Copper ( Proteinate) 10% Iodine (Potassium Iodide) 98% Iron (Proteinate) 15% Magnesium (Oxide) 58% Manganese (Proteinate) 15% Molybdenum (Sodium Molybdate Dihydrate) 39% Selenium (Sodium Selenite) 44.8% Zinc (Proteinate) 15% 1-Lysine (-HCl) d,1-Methionine Mixed Tocopherols Choline Chloride Sipernat 50 (Silicon Dioxide) Lodex-5 (Maltodextrin) Peanut Oil Soy Flour (17.5% Blend) Peanut Flour Sweet Whey BF70 Spice Dextrose Powder   0.569.511gm/lb1.5gm/lb1.5gm/lb1.5gm/lb15.750gm13.68gm2050.0021.629.7329.16IU0.0921120.3241.158600IU0.05543.0972.9IU10.000430.560.0053.31101.650.050.00162508.4111.03   0.0050.69510.241182.052.052.050.05250.04850.020.050.21620.0009730.7298IU0.0000920.0010060.0121570.01080.0011584.02IU0.0027760.003080.0729IU0.00070.0000430.01120.0000530.03310.040.040.0010.0000810.049870.08410.1103     0.056.912.411820.57120.5720.5715.084.8822.502.1620.009737.298IU0.000920.010060.121570.1080.0115840.212IU0.027760.03080.729IU0.0070.000430.1120.000530.3310.40.40.010.000810.49870.8411.103     10.001390.38482.203887.003887.00240.001010.00977.00400.00500.00432.502.001459.68IU0.182.1624.3121.602.328046.50IU5.550.16145.88IU1.400.08622.400.10666.2380.0066.422.000.2099.74176.91220.7760.00486.802553.351508.87496.564965.024965.02400.0029.20500.00

(*) Lactic acid-producing bacteria make up two-thirds of the ingredient and yeast one-third; lactic acid-producing bacteria 500,000,000 CFU/gm, yeast (eg "Saccharomyces") 250,000,000 CFU/gm

Table 4

Cat Premix Preparations

(Amounts in mg/lb body weight unless otherwise stated)

Element high Low Preferred Dosage: mg/2.2gm formula 1-Arginine*Lacto Yeast (4.9% blend) Montmorillonite Canola Oil (14.5% blend) Safflower Oil (14.5% blend) Linseed Oil (55% Alpha Linolenic Acid) (1.0% Blend) Phosphorus (Phosphoric Acid Sodium Dihydrogen) 12% Calcium Carbonate 8.5% (38% Calcium) Dimethylsulfone Transfer Factor Vitamin C (Ascorbic Acid) D-Biotin (Vitamin H2%) Vitamin D ₃ Vitamin B ₁₂ Folic Acid Niacinimide Pantothenic Acid (d-Calcium Pantothenate) 91.6 %Vitamin B ₆ (Pyridine Hcl) 82.3%) Vitamin A (Vitamin A Palmitate) 650M IU/g Feed Grade Vitamin B ₂ Thiamine (Mononitrate) 83% Vitamin E Vitamin K Cobalt (Protein) 5% Copper (proteinate) 10% iodine (potassium iodide) 98% iron (proteinate) 15% magnesium (oxide) 58% manganese (proteinate) 15% molybdenum (sodium molybdate dihydrate) 39% selenium (sodium selenite ) 44.8% Zinc (Proteinate) 15% 1-Lysine (-HCl) d, 1-Methionine Mixed Tocopherols Choline Chloride Sipernat 50 (Silicon Dioxide) Lodex-5 (Maltodextrin) Sweet Whey BF70 Spice Dextrose Powder HCl Glucosamine Pernaconniculus - Chondroitin  0.569.511gm/lb1.5gm/lb1.5gm/lb1.5gm/lb15.750gm13.68gm2050.0021.629.7329.16IU0.0921120.3241.158600IU0.05543.0972.9IU10.000430.560.0053.31101.650.050.00162508.4111.03   0.0050.69510.241182.052.052.050.05250.04850.020.050.21620.0009730.7298IU0.0000920.0010060.0121570.01080.0011584.02IU0.0027760.003080.0729IU0.00070.0000430.01120.0000530.03310.040.040.0010.0000810.049870.08410.1103   0.056.912.411820.57120.5720.5715.084.88216.002.1620.009737.298IU0.000920.010060.121570.1080.0115840.212IU0.027760.03080.729IU0.0070.000430.1120.000530.3310.40.40.010.000810.49870.8411.103     0.78108.4237.00323.25323.2522.1378.7075.6931.20250.0033.730.156113.90IU0.0140.1681.901.680.18627.60IU0.430.4811.38IU0.110.0061.750.0085.176.245.180.1560.1567.7813.8017.224.6838.0199.06117.30155.372.28250.00100.00200.00

(*) Lactic acid-producing bacteria make up two-thirds of the ingredient and yeast one-third; lactic acid-producing bacteria 500,000,000 CFU/gm, yeast (eg "Saccharomyces") 250,000,000 CFU/gm

table 5

stress preparation

(Amounts in mg/lb body weight unless otherwise stated)

Element high Low Preferred Dosage: mg/oz of formulation Calcium Pantothenate Vitamin C (Ascorbic Acid) Vitamin B ₁₂ Vitamin A Vitamin B ₂ Thiamine Vitamin E Magnesium Sulfate * Lactobacillus Acidophilus Sodium Chloride Dipotassium Hydrogen Phosphate Citric Yeast (Hydrolyzed) Glycine Potassium Chloride Vitamin D ₃ Glucose Artificial Flavor Transfer Factor Sipernat (Silicon Dioxide) 1.8020.0013.00600.00IU1.2016.0072.9IU10.0010.00166.00116.0031.00180.000.14218.0029.0040.000.02850.00 0.090.0560.130.10IU0.0650.03080.729IU0.1130.4670.2365.851.590.19570.01420.930.7292.000.00280.05 0.0280.0170.1980.0140.0180.0170.0120.1131.4182.3681.7730.4820.2830.1420.2830.00221.3828.5480.750.05 28.0017.00198.5914.0018.0017.0012.48113.001418.002368.001773.00482.00283.00141.80283.001.5621375.0028.30750.0056.70

(*)10 ⁹ colony forming units (CFU)/gm

Table 6

performance formulation

(Amounts in mg/lb body weight unless otherwise stated)

Element high* Low* mean* Dosage: mg/oz. Formula Superoxide Dismutase Glucosamine Transfer Factor ¹ (Horse, Bovine) Transfer Factor ¹ (Goat) Transfer Factor ¹ (Dog, Cat) Pernaconniculus-Chondroitin (Mucopolysaccharides) Boswellic Acids Di-Methylglycine Di Methylsulfone Octocosonol Montmorillonite 60.065.015.010.050.016.53027.027.02.030.0 0.60.650.150.100.50.1650.30.270.270.0040.3 6.06.51.51.05.01.653.02.72.70.043.0 6000.06500.01500.03000.014000.01650.03000.02700.02700.0400.03000.0

*These amounts are calculated for livestock animals weighing approximately 450-1,000 lbs, goats weighing approximately 150 lbs, and dogs and cats weighing approximately 8-15 lbs.

¹ The amount of transfer factor may vary from species to species, but the amounts of other components remain the same for each species.

Table 7

Livestock Stress Rumen Diverter

(Amounts in mg/lb body weight unless otherwise stated)

Element Dosage: mg/oz. (unless otherwise stated) formulation Stabilized ¹ transfer factor (mammalian source) transfer factor (avian source) beta-sitosterol (90% phytosterols) phytic acid olive leaf extract aloe extract powder (200:1) hybrid and non- Hybrid glucans (from hybrid Cordyceps, Agaricus blazeii, Miatake, Shitake, Coriolis, Inonotus, Obliquus, and Poriscocos mushrooms) Vitamin C Non-stabilized Vitamin A Vitamin D3 Vitamin E Vitamin B1 Vitamin B2 Vitamin B12 Dipotassium Hydrogen Phosphate Potassium Chloride Magnesium Sulfate Calcium Pantothenate Ascorbic Acid Lactobacillus Yeast (Saccharomyces cerevisiae) Protein Zinc 3500.01000.0300.0350.035.017.04000.02000.04434IU/oz1140IU/oz500IU/oz12.7712.771.51.5g/oz2078323232.5×10 ⁶ CFU/oz15.0×10 ^{6 10} CFU/oz

*These amounts are calculated for livestock animals weighing approximately 450-1,000 lbs, goats weighing approximately 150 lbs, and dogs and cats weighing approximately 8-15 lbs.

¹ Includes stabilized active ingredient in a formulation of 50% soybean oil and 50% active ingredient.

The following examples serve to more fully describe the manner of using the above invention and enumerate the best modes contemplated for carrying out various aspects of the invention. It should be understood that these examples are in no way intended to limit the true scope of the invention, but are provided for illustrative purposes. All patents, patent applications, publications and references cited herein are expressly incorporated by reference in their entirety.

Example 1

Group I

240 hybrid heifers were randomly divided into three groups of 80 calves each. They were weighed separately and they received a mixture of bovine infectious rhinotracheitis (IBR) virus, inactivated bovine viral diarrhea virus (BVD), attenuated-live bovine respiratory syncytial virus (BRSV) and inactivated Combination live attenuated virus vaccine consisting of parainfluenza-3 (PI3) virus, polyvalent bacterin toxoid against seven Clostridium species; dormectin dewormer (Ivomec); and progesterone implant. Ten days after treatment, calves were given a booster dose of the same live attenuated vaccine they had initially received. A group of 80 calves averaging 440.1 lbs received a 1 oz dose of the stress formulation listed in column 5 of Table 5 dissolved in 1 oz of water via a dosing syringe at the time of treatment. Thereafter, they were given a daily dose of 1 oz of the stress formulation mixed in the feed (Total Mixed Ratio - TMR) for 4 days after treatment. A second group of 80 calves averaging 440 lbs received 1.5 ml/cwt tilmicosin (Micotil) concurrently with the initial treatment. A third group of 80 calves averaging 449.9 lbs was used as a control group. The groups were observed for 26 days after treatment, at which time each calf was weighed again and feed efficiency was calculated jointly for each group.

Group II

200 hybrid stock heifers were randomly divided into four groups of 50 calves each. Treat them the same way as the stock in Group I. A group of 50 calves averaging 441 lbs received 1 ounce of the stress formulation listed in Table 4, column 5 daily in their TMR for 5 days. A second group of 50 calves averaging 433 lbs received 1/2 oz of the same stress formulation in their TMR for 5 days. A third group of 50 calves averaging 47 lbs received metaphylactic 1.5ml/cwt tilmicosin/cwt concurrently with the initial treatment. A fourth group of 50 calves averaging 432 lbs was used as a control group. Each heifer in all four groups received a booster dose of a live attenuated virus combination vaccine of IBR, PI3, BVD and BSV 10 days after the initial treatment. Groups were observed for 26 days after treatment, at which time each calf was weighed again and feed efficiency was calculated jointly for each group.

One-way statistical analysis of variance was performed on body weight gain. F-tests and LSD mean separations were performed using α = 0.05 as the first-type error rate. The software is SAS (1999), program GLM.

Statistical analysis of BRD incidence rates used: Chi-square analysis using Fisher's exact test, with a probability of 0.05 or less interpreting significance as explaining differences in incidence rates between groups.

The results are listed in Tables 8 and 9 below.

For Group I, 80 calves treated with 1 oz of stress formulation in 1 oz of water by dosing syringe on the day of treatment and 1 oz of stress formulation/day added to TMR for 4 days after treatment. There were no diseased pulls (ie diseased calves undergoing treatment) among the cows. There were 17 diseased pullouts and 4 redraws due to BRD in the control group, and 12 diseased pullouts and 1 redrawn in the tilmicosin group.

Heifers in Group I had a mean daily weight gain of 3.63 lbs over the 26 day test period, which was statistically significant when compared to the other two groups. Average daily body weight gain (ADG) was 2.96 and 3.08 pounds for tilmicosin and the control group, respectively. The feed efficiencies of the stress preparation, tilmicosin and the control group were 6.73, 6.94 and 6.66, respectively.

Heifers in the 1 oz stress formulation dose group in Group II had an average daily body weight gain of 3.2 lbs and those in the 0.5 oz stress formulation dose group had an average daily weight gain of 3.05 lbs , tilmicosin and the control group had mean daily body weight gains of 2.88 and 2.92 pounds, respectively. Feed efficiency was 5.31 for 1 oz of the stress formulation, compared to 6.09, 6.10, and 5.99 for half an oz of stress formulation, tilmicosin, and control, respectively.

There were 11 diseased pull-outs and re-draws for BRD treatment in a group of 50 heifers that received 1 oz of stress formulation/day added to the total mix ration for 5 days from the day of treatment, In the group receiving 1/2 oz TF in TMR for 5 days there were 13 diseased pull-outs and 4 re-draws for BRD. There were 5 diseased pull-outs and 2 re-draws from the tilmicosin group during the 30-day test period. In the control group, there were 11 pull-outs with BRD disease and 2 re-draws.

When comparing the differences in the proportion of sick pull-outs between groups within Group I, the stress formulation appeared to provide significant protection against BRD over the course of the 26-day test period. The stress preparation also significantly increased mean daily body weight gain.

In group II, heifers in two groups achieved better weight gain than heifers in the other two groups. However, in Group II, protection against BRD appeared to be lower than that of tilmicosin. When comparing the effects of TF on BRD between Groups I and II, the results appeared inconsistent until it was realized that the heifers in Group II did not receive the initial dose of the stress formulation via the dosing syringe during treatment. This evidence makes a strong case for administering the starting dose via dosing syringe or capsule to ensure that each subject receives at least the full first dose without relying solely on receiving the stressor via TMR. Heifers drawn for treatment in both stress formulation groups likely did not consume a full portion of TMR on the first critical stress day and thus did not receive sufficient stress formulation to stimulate the immune system.

When comparing heifers that received a full ounce of stress formulation per day to the group that received half an ounce per day, there were no significant differences in heifer performance. It is very likely that the difference might be even smaller if both doses were given initially by dosing syringe or capsule.

It should be noted here that the weight gain in the stressor group over the other groups in Group II more than adequately compensated for the cost of treating BRD in the stressor group.

In unpretreated at-risk cattle such as the heifers in these studies, direct stimulation of the immune system with a stress agent along with vaccine administration does appear to increase the level of immunity to BRD. Stress formulations have been shown to reduce the need for and or enhance the effectiveness of antibiotic therapy.

Table 8

Group I results

1 oz. stress preparation per day - take it on the first day, then apply it on the face on the next 4 days

therapy group number of heifers ADG Kg(lbs) Muscle strain muscle strain   Feed Efficiency diseased muscle strain Stress preparation (1oz/day) tilmicosin (Micotil1.5ml/cwt) control group 808080 3.632.963.08 200.0(440.1)200.0(440.0)204.5(449.9) 01217 014 6.736.946.66 1.651.351.40

Table 9

Group II Results

Daily stress preparation - 5 days face only

therapy group number of heifers ADG Kg(lbs) Muscle strain muscle strain   Feed Efficiency diseased muscle strain Stress preparation (1oz/day) stress preparation (1/2oz/day) tilmicosin (Micotil1.5ml/cwt) control group 50505050 3.203.052.882.92 200.5(441.0)198.8(433.0)203.2(447.0)196.4(432.0) 1113511 4422 5.316.096.105.99 1.451.391.311.33

Example 2

The Fort Bidwell, California herd has a chronic problem with calf dysentery with a mortality rate of 63% and a morbidity rate of 90%. This problem has persisted for 7 years. Treatments that did not produce improvement included the antibiotics tetracycline, mycotil, sulfur and Penicillium and other traditional treatments such as liquids and antidiarrheals such as kaolin and pectin preparations. The University of California, Davis and the University of Washington cannot provide a solution. Forty test calves weighing approximately 100 lbs were treated daily with 1 ounce of the stress formulation shown in Table 5, column 5, delivered in capsule form for 2 days, and 60 calves serving as controls received no substance. for prevention. In the test calf, one animal died because it was dosed too late, but none of the other test animals showed any signs of disease. However, the proportion of diarrhea in control calves was 90%, the same as in previous years. When calves were treated with stress agents immediately after a dysentery outbreak, the calves got better. New calves in the herd are currently treated in capsule form with 1 oz of the stress formulation shown in Table 5, column 5, and they show the same results as test calves with 1 capsule daily for 2 days. The last 20 calves in the herd that had been treated with the stress formulation regimen had been pastured and gained 7% body weight and had better coat and posture than the test calves. Neighboring largeholders with similar dysentery problems in calves have also begun testing stress formulation regimens and have had similar successful results.

Example 3

Forty egg donor cows lost all of their calves on a farm in Pennsylvania, and some of the adult cows also showed disease. The University of Ohio diagnosed cows and calves with Clostridium perfringens type A. Initial treatment of these cows and calves with several available antibiotics was unsuccessful. Calves had 100% morbidity and 80% mortality. The protocol begins with calves weighing approximately 80-100 lbs each treated with 1 ounce per day of the stress formulation shown in column 5 of Table 5 for 7 days from birth. Antibiotics were not given to these calves. About 30 calves have been treated since the program started, no dysentery was observed in the herd and no more calves died.

Example 4

A herd of 130 cows and calves in Columbus Nebraska suffered from chronic dysentery of coliform origin. About 60% of calves showed affliction. Treatment with antibiotics and fluids has produced moderate success, with a mortality rate of approximately 10%. Ten of the calves, each weighing approximately 80-100 pounds and suffering from this dysentery, were then treated daily for 3 days with 1 ounce of the stress formulation shown in Table 5, column 5. After 3 days on the regimen, the 10 calves no longer showed signs of dysentery. However, untreated calves still had problems with dysentery.

Example 5

Cats (2.2 gm/day as shown in column 5 of Table 4), dogs (28.37 gm/day as shown in column 5 of Table 3) and horses and cattle (as shown in column 5 of Table 2) were treated with the premix formulation. Benign tumors in more than 50 cases in the indicated 5oz./day). These tumors range from benign sarcomas to papillomas. Overall, tumors shrink by 40%-80% and even disappear completely in some cases. Malignancies such as Oral squamous cell carcinoma was reduced.

Example 6

100 cows weighing 450 lbs were trucked 2 hours from the ranch to the feedlot and were just weaned from the cows. Fifty of the vaccinated cattle were treated by conventional vaccination and insecticide deworming and one injection of Micotil and served as a control group. Another 50 cows were vaccinated, dewormed and each given 1 ounce of a solution containing 1500 mg of transfer factor and 1418 mg of lactic acid producing bacteria as shown in Table 5. This dose was administered orally to each test cow for a further 4 days. After 30 days of administration of transfer factor and lactic acid-producing bacteria, the test cows were each 10 pounds heavier than the Micotil-treated cows.

Example 7

There was a severe Clostridium perfringens type A outbreak in 100 calving cows with 80% morbidity and 30% mortality in conventionally treated calves. Calves weighing approximately 110 lbs were given 750 mg of transfer factor and 1418 mg of Lactobacillus acidophilus (10 ⁹ colony forming units (CFU)/gm) each for 2 consecutive days, the incidence of Clostridia decreased to 20%, and death rate down to 5%.

Example 8

500 original breed cattle weighing approximately 600 lbs were each brought from the ranch to the feedlot after 6 hours of trailer transport and immediately treated (ie, insecticide dewormed and vaccinated). 750 mg of transfer factor, 283 mg of yeast and 2368 mg of lactic acid were given to 250 or every other calf according to Table 5. Other calves were treated, some were given Micotil and others were given Liquarnycin and sulfonamides in order to test different products at recommended doses. After 40 days, the transfer factor, yeast and Lactobacillus calves weighed 12 pounds more than the other calves and had 30% less disease in the calves in the transfer factor etc. group than the other calves. Slaughter yield data showed significant improvement in large ribeye, lower slaughter waste and higher yield in cattle using transfer factor.

Example 9

Clostridium perfringens type A chronic dysentery among first born calves in a herd of 100 dairy cows on a small dairy farm. Still losing calves using conventional treatments. The remaining calves were treated daily for 5 days after their birth with a formulation of 1300 mg of transfer factor and 1418 mg of lactic acid producing bacteria and 283 mg of yeast as shown in Table 5, which were mixed into the solution and fed to each calf. Morbidity was reduced by 60% and mortality by 80%.

Example 10

This example compares the oral administration of bovine transfer factor with a metaphylactic antibiotic (Micotil) in the treatment of calves and their effect on the performance and health of stressed fattening cattle.

Approximately 600-700 feeder cattle (400-500 lb each) were penned and provided with clean drinking water and longstem hay ad libitum prior to treatment. Body weight and rectal temperature were recorded for each animal within 24 hours of arrival. Cattle are randomly manipulated through processing equipment and uniquely identified using numbered ear tags. Each animal was treated for internal and external parasites (Phonectin) and vaccinated against common viral (Bovishield 4) and Clostridium (Fortress-7) diseases.

Calves from each load were sorted in four ways into groups of 23-28 head. Every other animal received a 1-oz oral dose of non-encapsulated bovine transfer factor as shown in Table 5 (given as an oral liquid veterinary drench), and the remaining animals received 1.5 ml/100 lb BW of Micotil. On days 2, 3, 4, and 5, animals in the designated bovine transfer factor groups were supplemented with 1 oz/head/day of bovine transfer factor as a quantitative face-coat. Randomly assign groups to consecutively numbered pens. Cattle were re-vaccinated with a 4-way virus vaccine (Bovishield-4) on day 7 after the initial treatment and temperatures were recorded.

The experimental diet provided approximately 45% roughage and 55% concentrate. The amount of feed provided to each pen of cattle was determined each morning at approximately 0700 hours. Cattle were fed enough so that there was only traces of unconsumed feed in the trough on the second morning. The full daily ration for each pen was delivered at approximately 0800 hours each day. In case of overfeed, remove remaining feed from trough to prevent spoilage. Feed removed was weighed and taken into account in subsequent calculations of feed consumption.

Animals were monitored daily for clinical signs of respiratory disease and cattle exhibiting clinical signs of respiratory disease including depression, lethargy, anorexia, coughing, shortness of breath, nasal and/or ocular discharge were identified as candidates for treatment. Animals were assigned a clinical score ranging from 1 to 4. A clinical score of 1 identifies mild respiratory disease, a clinical score of 2 indicates moderate disease, a score of 3 indicates severe respiratory disease, and a clinical score of 4 indicates moribund animals. Animals with an assigned clinical score of 1 or greater were removed (drawn) from the pen and brought to the handling area for measurement of body weight and rectal temperature. Animals with a clinical score of 1 or greater received antibiotic therapy.

All animals treated received the standard regimen for respiratory disease, including subcutaneous injection of tilmicosin (Micotil) at a dose of 10 mg/kg. Rectal temperatures were recorded and cattle were returned to their original pens following treatment. Repeat treatment after 48 hours if necessary. Information relating to morbidity, mortality, body weight gain and feed intake was collected throughout the experiment.

At the end of the reception period, the cattle were weighed individually and a 10-ml aliquot of blood was retained for plasma recovery. The receiving pens were combined so that cattle from each treatment were equally distributed into each of the two pastures. The cattle are then transported for summer grazing on natural pastures. Upon completion of the grazing period, cattle are collected from pasture and transported for final processing. Cattle were distributed among 4 feedlot pens, with cattle from 6 pens combined into a single feedlot pen (approximately 150-180 head).

The results from this experiment are listed in Table 10. As can be observed, these transfer factor treated animals had significantly higher antibiotic treatment withdrawal rates than Micotil treated animals, i.e. 73% vs. 48% for the first treatment and 0 for the second treatment 32% vs 14%, and 17% vs 50% for the third treatment.

These results suggest that transfer factor does not work as well as tilmicosin when used to treat stressed cattle.

Table 10

project Tilmicosin transfer factor head count starting weight, lb starting rectal temperature, deg F7-day body weight, lb7-day rectal temperature, deg F dry matter intake, lb last 7 days last 21 days first treatment, total % re-treatment, total % Third Treatment, % Total Deaths, % Total 333492.1102.5502.2102.412.89.848.0514.114.500.60 332495.6102.6506.3102.312.19.673.4931.9317.470.30

Example 11

In vitro protein degradation. Ruminal fluid was incubated in vitro alone (control group), with casein or with TF. Rumen contents were obtained from 2 rumen-intubated Jersey beef cattle fed a diet containing 76% steamed cornflakes, 10% alfalfa hay, 3% soybean meal, 1.2% urea, 5% cane molasses, and 4.8% mineral Vitamin premix (DM base), for ad libitum intake. The entire rumen contents were strained through two layers of cheesecloth and an attempt was made to remove any particle-bound organisms by washing the solid residue left on the cheesecloth four times with a prepared McDougall's buffer. The total volume is equal to the original volume of the strained rumen fluid. The strained rumen fluid and buffer solution mixture was then filtered through eight layers of cheesecloth and combined.

The final inoculum contained (per liter) 450 mL strained rumen fluid, 450 mL buffer extract from washed solids, 234 mg 2-mercaptoethanol, 50 L maltose solution containing 100 mg/mL maltose, 25 mL 60 mM hydrazine sulfate solution, and 25 mL containing 1.80 mg/mL chloramphenicol solution. Hydrazine sulfate and chloramphenicol were added in an attempt to inhibit microbial uptake and metabolism of _NH3 and AA.

40 mg N from casein or stress preparation (N concentration of casein and stress preparation predetermined according to Kjeldahl N ¹⁶ analysis) was weighed into a 500 mL Erlenmeyer flask and 100 mL McDougall's buffer was added. Flasks containing buffer alone (control), buffer + casein, or buffer + stress formulation were then incubated for 1 hour at 39°C in a temperature-controlled chamber. A total of 12 flasks were used with four replicates for each treatment.

In vitro incubations were initiated by adding 200 mL of inoculum to each flask while purging with _CO2 . Incubations were performed for a period of 4 hours and 1-mL samples were collected immediately after addition of the inoculum (0 hours) and every 30 minutes thereafter. At the time of sampling, 1-mL samples were placed into disposable microcentrifuge tubes containing 0.25 mL of chilled 25% w/v trifluoroacetic acid and stored at -20°C until subsequent analysis.

For analysis, samples were thawed at room temperature and ^then centrifuged at 21,000 xg for 15 min and the resulting supernatant analyzed for NH _and total amino acid concentrations using a Technicon III AutoAnalyzer ^f as described by Broderick and Kang.

Calculation of protein degradation rate. Despite the in vitro incubation over the course of 4 hours, _NH3 and total amino acid concentrations only increased over the course of 1.5 hours, after which the _NH3 and total AA concentrations began to decrease, suggesting that _NH3 and total amino acids were taken up by the microorganisms. Therefore, only time points between 0-1.5 hours were used in the calculation of in vitro protein degradation rates. In vitro protein degradation at each time point was calculated using the following formula: % protein degradation = blank corrected value ([ _NH3 -N]) + ([total amino acids - N]) / mg N added to the flask. The percent undegraded protein at each time point was calculated using the following formula: 100 - percent undegraded protein.

Statistical analysis. Protein degradation rates were determined using regression analysis regressing the natural logarithm of the percent undegraded protein versus time. The resulting slope represents the protein degradation rate in fractions/hour. Slopes representing protein degradation rates were analyzed using ANOVA ^g where flasks were used as experimental units and the model effect consisted of protein source.

Example 12

A cattle feedlot operation with 3,800 feeder cattle participated in the study using the compositions detailed in Table 7. Typical practice for much of the industry is to purchase fattening cattle from large farms or sales sheds and then transport the cattle to feedlots. Animals generally weighed 350-550 lbs on arrival. Cattle are treated, fed and eventually brought to market weight. The feedlots participating in this study used the following treatment regimens over several years: Micotil at 1.5cc/cwt; TSV-2 (intranasal IBR-PI-3); Triangle 4 (IBR-PI-3, BVD, BRSV, Pasturella hemolyticum and Haemophilussomis); ivermectin (drench); chlortetracycline given at a rate of 80 mg per day in chopped mixed forage including traces of inorganic salts, Lasts 21-days. During the first 1 year of the study, the above regimen resulted in 15 animal deaths (3.9%), 1140 animals became ill (30%), and 200 developed chronic lung disease (lung disease patients) (5.3%). The programs of the participating feedlots produced statistical values similar to or better than the national average for 3,800 cattle with a mortality rate of 247 (6.4%) and a morbidity rate of 25% -35%.

During the course of the study, the standard regimen of participating feedlots was supplemented with the compositions detailed in Table 7. Regimen supplementation consisted of three consecutive treatments, each consisting of a single oral administration of 1 oz. capsule on day 1 followed by 1 oz. of the topical formulation on 2 consecutive days.

The results of this study reflect a significant and exceptional improvement over the previous year as well as the national average by adding the composition detailed in Table 7 to the previous regimen. Specifically, mortality was reduced by 90% to 15 (0.39%), morbidity was reduced by 68% to 342 (9%), and chronic lung disease was reduced by 84% to 32 (0.84%).

In addition to the improved mortality and morbidity results, this study also reflected that the addition of the compositions detailed in Table 7 to the previous regimen resulted in a significant increase in body weight gain. In the previous treatment regimen, the average weight gain in the first 30 days was 45 lbs. On the supplemented regimen, the average weight gain in the first 30 days was 80 lbs.

Example 13

The persistent and ongoing struggle to maintain acceptable Bulk Tank Somatic Cell Counts (BTSCC) represents one of the single greatest financial drains on the dairy industry. The individual cost of treatment can exceed $250 per cow. A recent study indicated that 34.5% of all cows had an SSC in the 200,000-229,000 range. The increasing pressure to reduce antibiotic use, the emergence of resistant microbial strains and the recent upward trend in national BTSCCs further demonstrates the seriousness of this problem and the growing need to reduce and maintain reduced somatic cell counts. Financial incentives in the form of quality bonuses add additional importance to SCC control. Therefore, a study was conducted to determine whether the compositions detailed in Table 7 could be used to effectively reduce BTSCC.

The study included 26 cows selected for high somatic cell counts. The control group (13 cows) had an initial mean SCC of 1,854,811. The treatment group (13 cows) had a starting mean SCC of 2,374,000. Cows in the control group received the standard regimen during the 60-day study period. Treated cows received 1 oz. of the composition detailed in Table 7 for 3 consecutive days, followed by a 3-day rest period for a total of three cycles (nine treatments total).

SCC testing of the control and treatment groups after 26 days revealed that the control group had 2,049,636 SCCs (10.5% increase) while the treatment group had 957,455 SCCs (59.7% decrease). Thus, the treatment group had an improvement of 70.2%, better than the control group. In addition, SCC counts at the 90-day test showed a 26% reduction in SCC, indicating a residual effect of the composition.

Example 14

64 high stress stock cattle were purchased and 32 (treatment group) were initially given two 1 oz. capsules containing the composition detailed in Table 7, while the remaining 32 (control group) remained untreated. The treatment group was also given 1 oz. of the composition daily for an additional 2 days. Neither the treatment group nor the control group received antibiotics. After 3 weeks, 5 calves from the treatment group required treatment due to morbidity, while 12 calves from the control group required such treatment (60% improvement in morbidity reduction). Furthermore, although 1 calf died in the control group, no calves died in the study group.

Example 15

Each of the seven goats suffered from severe pink eye, Chlymidia, other bacterial infections or were nearly blind. All 7 goats were treated with standard medication for 3 weeks with little or no improvement. All diseased goats were then given 1 oz. of the composition detailed in Table 7 daily for 14 days. Two goats with outbreaks stopped progressing within about 48 hours, and the other goats returned to normal within 10 days, with no eye scarring and fewer warts in the infected goats. Antibiotics were not used in this regimen.

Example 16

Growth of fungi of the genus Cordyceps

The ideal medium for growth of Cordyceps on a solid substrate is as follows: 1 part white millet (hulled) - 4 parts white sorghum (hulled) supplemented with 0.8% w/w oyster meal and 1% w/w vegetable oil (peanut oil or soybean oil). Water is added to equal 50% of the total moisture in the sterile substrate. Precooking the grain mixture for 4-6 hours followed by sterilization tended to induce a more rapid growth response of Cordyceps. On this medium, Cordyceps can grow for long periods of time, with near complete conversion of substrates to mycelia and complete expression of secondary metabolites from Cordyceps. The resulting Cordyceps was about 3-4% residual grain or about 96-98% pure mycelium when grown on this substrate. The real benefit of this growth method is that the full gift of extracellular metabolites produced throughout the full growth process is captured. Due to the addition of certain growth-initiating compounds to the mixture, Cordyceps sinensis is readily induced to produce fruiting bodies in culture in the absence of any insect matter. However, the formation of fruiting bodies on this medium did not produce any significant changes in the analytical chemical properties.

Using the aforementioned substrates, the complete chemical identity of cultivated Cordyceps remains inaccessible to wild-collected Cordyceps unless it is grown under very specific conditions. Cordyceps sinensis produces a relatively large amount of free adenosine when grown at normal air oxygen levels and room temperature. It also produces large amounts of uridine and guanosine. Only very small amounts, if any, of cordycepin were produced, and virtually no hydroxyethyladenosine. In the case of an organism that produces these compounds, it requires stress to grow through the absence of oxygen, a drop in temperature and complete absence of light. Just growing under cold and anaerobic conditions from the start is not helpful because when Cordyceps is grown under those conditions it forms yeast-like anamorphs with very different chemical properties. They must first be grown under hot and fast conditions, and then induced to convert their "summer" metabolites into target pharmaceutical compounds. To obtain these target compounds, a strict growth protocol was followed. Cordyceps were grown for 28-30 days at 20-22°C in diffuse light and sea-level air oxygen after inoculation on ground/milor millet substrate. It is then moved into a controlled environment chamber where the oxygen is reduced to 50% air oxygen, which is about 10% oxygen. The remainder of the growth air consists of nitrogen, carbon monoxide and carbon dioxide. The temperature was lowered to 3°C and all light was excluded. Keep it in these conditions for about 15-20 weeks. This process results in the conversion of most of the adenosine to cordycepin, dideoxy-adenosine and hydroxyethyl-adenosine. A number of other unique nucleosides were also produced, with the final chemical properties fully matching that of wild Cordyceps.

Example 17

Hybrid dextran preparation

Once the substrates and growth parameters were determined for optimization of target compounds, differences in chemical properties from different strains of Cordyceps sinensis were determined. Since there are so many Cordyceps strains and each strain has its own unique chemical characteristics, all obtained strains were tested. None of the known strains were confirmed to produce amounts of active components approaching those found in wild Cordyceps. In order to quantitatively increase the yield of the target compound, hybridization experiments of the Cordyceps strains were performed; they were hybridized to obtain a greater yield of the target compound. Various experiments were performed in order to obtain different fungal strains performing their own nuclear fusion. For example, niacin can be used to generate hybrid mycelia. This compound is difficult to use and produces unreliable results. After trying several different compounds to cause this fusion, it was found that snake venom worked best.

Venom for hybridization experiments was purified from the western diamondback rattlesnake (Crotalus atrox) [Sigma Scientific, St. Louis, Missouri, USA]. The venom was added to the agar medium in an amount which altered growth but proved not to be toxic to the strains described. The consumption range of this snake venom is 10mg-30mg/300ml agar medium. The venom is heat labile and must be added aseptically after the medium has been sterilized. The agar used for this hybridization is Aloha Medicinals, Inc., Maui, Hawaii proprietary agar called R7 Agar, which consists of wort, activated charcoal, minerals, and humus—the carbon-rich ash residue from the coal-burning industrial process . The exact formulations are listed in Table 11. Other agars can also be used.

Table 11

Snake Venom/R7 Agar Prescription

2.1L distilled water 50g light wort 34g Agar 10g Humus 5g   Activated carbon 1g _MgSO4 10ml 1% KOH solution base on needs Rattlesnake (C.atrox) venom

Petri dishes of this R7 agar medium were inoculated with mycelia from two different Cordyceps strains. These are usually two species of Cordyceps sinensis, however, we have also crossed Cordyceps with other species of the genus Cordyceps, such as Cordyceps militaris, Cicada velvet and Macrocystis. These different strains, when co-inoculated on a Petri dish, generally grow towards each other until they almost meet, at which point they form a zone of inhibition in which neither strain can grow. Eventually, one strain may be stronger than the other and overgrow on the plate, but they remain genetically distinct; two different cultures populate the same Petri dish.

Sufficient venom is added to the agar and the two cultures grow towards each other until they meet and form their mutual zone of inhibition. However, this period of inhibition is short-lived, with only about 2 or 3 hours before the colonies each begin to send mycelial strips into the zone of inhibition. These hyphal strands grow together and exchange nuclear material through their venom-weakened cell walls. They form hybrids at this point of mutual contact of new hybrid strains that are distinctly different from the parental strains. Within about 4 hours after the initial formation of the zone of inhibition, hybridization was complete and the colonies resumed growing rapidly toward each other. They became three colonies, two original and one new hybrid.

Carefully remove a portion of the newly formed hybrid from the original zone of inhibition at the exact time when the colony begins to fuse. That is, during the 3-4 hours after the initial encounter of the colonies. Hybrids were transferred to new Petri dishes containing normal (non-venom) agar. One method of determining hybridization consists in inoculating new plates containing normal agar with all three strains, the two originals and the suspected hybrid. If hybridization had actually occurred, they would now be three distinct colonies and would form mutual three-way zones of inhibition. If hybridization does not occur, then the suspected hybrids tend to fuse with each other or with another original colony, thereby confirming that the suspected hybrids are prone to fusion with one or the other of the original colonies, confirming that the suspected hybrids are not genetically different from the original strain.

Once the hybrids were confirmed, their growth parameters were tested. If vigorous and hardy growth occurs on the substrate, it is allowed to grow a certain amount of mycelium, and the active fraction is collected and analyzed. By repeating the test in this manner, hybrid strains were prepared that were readily grown in solid substrate culture, had higher potency than any other cultivated strain and were at least equal in potency to the highest quality wild Cordyceps. This new strain is Cordyceps sinensis Alohaenis.

Example 18

Treatment of Stressed Cattle

The transfer factor formulations listed in Table 7 were used to study live stock cattle under stress. Calves were given this ruminal shunt formulation at a rate of 1 oz/head/day for 4 days. 318 calves were treated with the transfer factor preparation. There were 180 calves in the control group. All calves were vaccinated and kept warm.

Results from this experiment appear in Figure 1 of the accompanying drawings. As can be observed, the incidence in the control population was approximately 15.5%, while the incidence in the transfer factor treated population was 3.1%. Furthermore, the mortality rate in the control group was 5.5%, while the mortality rate in the transfer factor-treated group was 0%. The control group had a daily weight gain of 1.85 lbs/day, while the group treated with transfer factor had a daily weight gain of approximately 3.05 lbs/day.

Example 19

In another study, 585 calves were treated with 1 oz of the transfer factor formulation of Table 7 daily for 3 days and treated with 1 oz of the formulation of Table 7 during revaccination on day 12. A control group of 29 calves did not receive the formulation of Table 7. All calves in this study received vaccines and antibiotics (Micotil or A-1A) and insecticide deworming (Ibomec). The calves are grown for 4-6 days to 45 days, horns are dehorned and all bulls castrated if necessary. Average daily body weight gains were calculated based on entry and exit body weights at the facility.

As can be observed in Figure 2, the incidence in the control group was 83%, whereas the incidence in the transfer factor treated group was only 2.6%. Similarly, the mortality rate in the control group was 24.1%, compared to 0% in the transfer factor-treated group. In each case, deaths in the control population were the result of bovine respiratory disease. Furthermore, daily body weight gain in the control group was less than 1 lb/day, whereas those animals treated with transfer factor achieved a body weight gain of approximately 3.1 lb/day.

Appendix 1. Human and Bovine Pathogens:

potential cross reactivity

human pathogen or disease Commonality bovine pathogen Bacterial Traveler's Disease (E. coli) Bloody Diarrhea/Hemolytic Uremic Salmonella Infection/Salmonella Typhi Diarrhea due to food or water Clostridium infection (non-tetanus) Clostridium difficile Mycobacterium infection Johnei, Gram Rohn's disease Staphylococcus superinfection Streptococcal infection Endocarditis Superinfection Streptococcus pyogenes Enterococcus hospital/VRE strains Severity of Helicobacter pylori (ulcers) very very increase common very common common common common increase increase common common common Toxigenic Escherichia coli Campylobacter jejuni Escherichia coli 0157:H7 Verotoxic Salmonella typhimurium, dublin Campylobacter jejuni Clostridium (many species) Mycobacterium species common in Jersey cattle Staphylococcus aureus Streptococcus Beta Streptococcus pyogenes Coccus Enterococcus (most species & VRE) bovine/pig combination Viruses Influenza Pneumonia Respiratory Syncytial Virus Papilloma, Condylomaya Viral Diarrhea Rotavirus Cytomegalovirus Herpes HIV (retrovirus) Rhinovirus (common cold) common common common common common common very Influenza virus Bovine respiratory syncytial virus Bovine papillomavirus Bovine viral diarrhea Rotavirus coronavirus Bovine CMV and IBR Bovine rhinotracheitis Bovine immunodeficiency virus Bovine rhinovirus Yeast, Fungi and Protozoa Candidiasis Cryptosporidiosis Giardiasis common very common Candida exp. Common calf diarrhea, C. parvum calf diarrhea, G. lamblia Other mycoplasma pneumonia, arthritis common Mycoplasma bovis pneumonia

Appendix 2. Human and Avian Pathogens:

potential cross reactivity

human pathogen or disease Commonality avian pathogen Bacterial Traveler's Diarrhea (E. coli) Bloody Diarrhea/Hemolytic Uremic Diarrhea Salmonella Infection Diarrhea due to Food or Water Clostridium Infection Pasteurellosis Pneumonia Systemic Infection Diarrhea, Systemic Infection very very increase very very common very common common common very Toxigenic Escherichia coli Campylobacter jejuni Escherichia coli 0157:H7 verotoxic01, 02, 047, other Salmonella species Campylobacter jejuni Clostridium species Pasteurella multocida Haemophilus gallinarum Mycoplasma pneumoniae Chlamydia pneumoniae Erysipelas suis Listeria monocytogenes Viruses Varicella Influenza Infectious Bronchitis Adult Leukemia Virus (ATLV-1) Pneumonia Herpes Infection very very common rare common common Avian Pox Influenza Virus Infectious Bronchitis Marek's Disease Virus Paramyxovirus Herpes Simplex Virus Fungal pneumonia, systemic disease diarrhea, systemic disease diarrhea, thrush, vaginitis systemic disease systemic disease very very very very very very Aspergillus species Aspergillus species Candida albicans Capsular Histoplasma Coccidia parasite trichomoniasis diarrhea very very Trichomonas Giardia

Claims (41)

CLAIMS 1. A method comprising administering to an animal a transfer factor formulation, wherein said formulation comprises transfer factor encapsulated with a hydrophobic or lipid coating. 2. The method of claim 1, wherein the hydrophobic coating comprises essential fats and/or vegetable oils. 3. The method of claim 2, wherein said vegetable oil comprises soybean oil. 4. The method of claim 1, wherein said formulation further comprises dextran. 5. The method of claim 4, wherein the dextran is a hybrid dextran. 6. The method of claim 4, wherein the dextran is encapsulated with a hydrophobic or lipid coating. 7. The method of claim 6, wherein the hydrophobic coating comprises essential fats and/or vegetable oils. 8. The method of claim 7, wherein said vegetable oil comprises soybean oil. 9. The method of claim 1, wherein the transfer factor is a targeted transfer factor. 10. The method of claim 9, wherein the targeted transfer factor is targeted to Herpes Simplex Virus 1, Herpes Simplex Virus 2, Helicobacter pylori, Champhobactor or Chlamydia. 11. The method of claim 1, wherein said administering is for prophylaxis. 12. The method of claim 1, wherein said administering is for the treatment of a pathological condition. 13. The method of claim 12, wherein said pathological condition is selected from the group consisting of heart disease, inflammatory disease and vascular disease. 14. The method of claim 1, wherein said administering is to increase the efficiency of food conversion. 15. A composition comprising transfer factor encapsulated with a hydrophobic or lipid coating. 16. The composition of claim 15, wherein the hydrophobic coating comprises essential fats or vegetable oils. 17. The composition of claim 16, wherein said vegetable oil comprises soybean oil. 18. The composition of claim 15, further comprising dextran. 19. The composition of claim 18, wherein the dextran is a hybrid dextran. 20. The composition of claim 18, wherein the dextran is encapsulated with a hydrophobic or lipid coating. 21. The composition of claim 20, wherein the hydrophobic coating comprises essential fats and/or vegetable oils. 22. The composition of claim 21, wherein said vegetable oil comprises soybean oil. 23. The composition of claim 15, wherein the transfer factor is targeted transfer factor. 24. The composition of claim 22, wherein the targeted transfer factor is targeted to Herpes Simplex Virus 1, Herpes Simplex Virus 2, Helicobacter pylori, Champhobactor or Chlamydia. 25. A method comprising administering to an animal a formulation comprising dextran, wherein said dextran is encapsulated with a hydrophobic or lipid coating. 26. The method of claim 25, wherein the dextran is a hybrid dextran. 27. The method of claim 25, wherein the hydrophobic coating comprises essential fats and/or vegetable oils. 28. The method of claim 27, wherein said vegetable oil comprises soybean oil. 29. The method of claim 27, wherein said formulation further comprises transfer factor. 30. The method of claim 29, wherein the transfer factor is encapsulated with a hydrophobic or lipid coating. 31. The method of claim 30, wherein said hydrophobic coating of said transfer factor comprises essential fats and/or vegetable oils. 32. The method of claim 28, wherein the vegetable oil encapsulating the transfer factor comprises soybean oil. 33. A composition comprising dextran encapsulated with a hydrophobic or lipid coating. 34. The composition of claim 33, wherein the dextran is a hybrid dextran. 35. The composition of claim 33, wherein the hydrophobic coating comprises essential fats or vegetable oils. 36. The composition of claim 35, wherein said vegetable oil comprises soybean oil. 37. The composition of claim 33, further comprising transfer factor. 38. The composition of claim 37, wherein the transfer factor is encapsulated with a hydrophobic or lipid coating. 39. The composition of claim 38, wherein said hydrophobic coating of said transfer factor comprises essential fats or vegetable oils. 40. The composition of claim 39, wherein said vegetable oil comprises soybean oil. 41. A composition comprising transfer factor and hybrid dextran.

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