HU0400589A2 - Colostrum-based composition - Google Patents

Colostrum-based composition Download PDF

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Publication number
HU0400589A2
HU0400589A2 HU0400589A HU0400589A HU0400589A2 HU 0400589 A2 HU0400589 A2 HU 0400589A2 HU 0400589 A HU0400589 A HU 0400589A HU 0400589 A HU0400589 A HU 0400589A HU 0400589 A2 HU0400589 A2 HU 0400589A2
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Hungary
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colostrum
composition
derived
milk
hyperimmune milk
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HU0400589A
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Hungarian (hu)
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HU0400589A3 (en
Inventor
Peter Graeme Hobman
Charles Edward Williams
Simon Stephen Yarrow
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Fonterra Co-Operative Group Limited
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Application filed by Fonterra Co-Operative Group Limited filed Critical Fonterra Co-Operative Group Limited
Priority to PCT/NZ2001/000256 priority patent/WO2002040051A1/en
Publication of HU0400589A2 publication Critical patent/HU0400589A2/en
Publication of HU0400589A3 publication Critical patent/HU0400589A3/en

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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/14Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from fungi, algea or lichens
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K35/00Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/20Milk; Whey; Colostrum
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K39/395Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A61K39/40Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum bacterial
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00Drugs for skeletal disorders
    • A61P19/02Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00Non-central analgesic, antipyretic or anti-inflammatory agents, e.g antirheumatic agents; Non-steroidal anti-inflammatory drugs (NSAIDs)
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04Antibacterial agents
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/04Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies from milk
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/12Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria
    • C07K16/1203Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria from Gram-negative bacteria
    • C07K16/121Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria from Gram-negative bacteria from Helicobacter (Campylobacter) (G)
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/12Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria
    • C07K16/1203Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria from Gram-negative bacteria
    • C07K16/1228Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria from Gram-negative bacteria from Enterobacteriaceae (F), e.g. Citrobacter, Serratia, Proteus, Providencia, Morganella, Yersinia
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/12Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria
    • C07K16/1267Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria from Gram-positive bacteria
    • C07K16/1282Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria from Gram-positive bacteria from Clostridium (G)
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K2039/505Medicinal preparations containing antigens or antibodies comprising antibodies
    • Y02A50/482

Abstract

The present invention relates to a composition comprising a colostrum or colostrum-like product and a hyperimmune milk product (HIM) or a product derived from hyperimmune milk in amounts sufficient to provide a broad spectrum of pathogenic pathogen binding activity of pathogenic organisms. - Anti-infectious agents for the treatment of an infectious disease, - The use of colostrum or colostrum product and a product containing hyperimmune milk (HIM) or hyperimmune milk in the manufacture of a medicament for the treatment or prophylaxis of infection-related and inflammatory disease. Compositions and methods of the invention may be used to treat or prevent an infection-related and inflammatory disease in clinical practice. HE

Description

The present invention relates to a colostrum-based composition for use in the treatment of an infection-related disease, including gastrointestinal (GI) and joint (disease) management.

Common infections of the gastrointestinal tract, such as bacteria, yeast, or parasitic pathogens that can cause acute infections (gastroenteritis such as Salmonella, Shigella or viral infections) or chronic infections such as Campylobacter jejuni-v & \ , Closrtidium difficile and Yersina enterocolitica. In general, the host immune system will cope with the presence of such pathogens. Under certain circumstances, however, pathogens such as Yersina enterocolitica and Helicobacter pylori can colonize the stomach and intestine and cause serious disease.

In a healthy animal (and human), the pathogenic microorganisms are controlled by the immune system. Immunoglobulins play an essential role in the immune system. Immunoglobulin G (IgG) is the most abundant immunoglobulin in all animal species (and humans). Clinical studies have shown that cow's milk contains specific antibodies against both enteropathogenic and enterogenic organisms.

Immunoglobulins are transmitted from mother to offspring in all mammalian species, thereby providing passive immunity to the newborn animal. In humans and monkeys, IgG and ancillary antibodies cross the placenta to the fetus during pregnancy and pregnancy. in the second two thirds of pregnancy. Passage appears to be selective in the sense that other immunoglobulins do not pass. In bovine animals, passive immunity is conferred by secretion of immunoglobulins, particularly IgG, into the colostrum produced by the cow during the first few days after calving, and by absorption of the immunoglobulins in the gastrointestinal tract. Absorption is selective in the sense that IgG is predominantly transmitted to the intestinal wall relative to other immunoglobulins.

Cow's milk antibodies have been shown to be effective in locally protecting against diseases caused by pathogenic microorganisms. Studies have shown that specific antibodies in cow's milk are active against enteropathogenic and enerotoxic Escherichia coli, cryptospridium, rotavirus and Shigella flexneri.

- 2 Hyperimmunized milk ("HIM") can be obtained from a cow which has been subjected to hyperimmunization with proprietary antigens in order to increase the concentration (ie titer) of specific antibodies active against the selected antigen. Such methods lead to the production of unique dairy products containing increased amounts of biologically functional antibodies and immunomodulators. HIM is known to be beneficial in preventing certain diseases by enhancing the body's natural resistance to the disease-causing antigens.

It is also a recognized fact that HIM contains ingredients that have anti-inflammatory activity and may be effective in treating joint disease.

Gangliosides, especially GM 3 and GD3, are a key component of the plasma membrane of all human cells, and are particularly prevalent in the nervous system. They play an important role in cell-cell recognition, cell signaling, and cell growth. Gangliosides are polar, complex phospholipids and contain a ceramide backbone attached to a sugar chain. The sugar chain contains an acid sugar, N-acetyl neuraminic acid (sialic acid).

Gangliosides are important constituents of breast milk (human milk) and cow's milk. The proportion of gangliosides in breast milk varies during different periods of milk production (lactation). For example, initially GD 3 is predominant, while GM 3 (amount) increases with milk selection, and after about a month it will be the major ganglioside. Gangliosides have three major physiological functions: they block the action of certain pathogens, promote neuronal growth and its repair mechanisms, and play a role in the regulation of cell growth and differentiation. Pathogens such as E. coli, with their ability to prevent rotavirus and Helicobacter pylori adhesion, have the potential to make them useful (useful) in preventing intestinal infections in the gastrointestinal tract and as an anti-ulcer agent. Idota et al., Idota et al., Biosci., Biotech. Biochem. 59 (1): 69-72 (1995)] demonstrated that GM 3 and GD 3 gangliosides reduced the binding of E. coli to human intestinal cells.

The high concentration of gangliosides in the human brain and its effects on nerve growth potentially make them useful for learning to cure graves and Alzheimer's disease. Low concentrations of gangliosides in the brain, for example, have been associated with irreversible impairment of learning (ability) in rats. In addition, external administration of gangliosides has been shown to provide partial protection in experimentally induced allergic neuritis, and gangliosides accelerate neuronal reperfusion / r processes in an in vivo cat model. In connection with cell growth and cell development, GM3 ganglioside binds to epidermal growth factor (EGF) and inhibits EGF-dependent receptor tyrosine autophosphorylation and cell growth. Reduced levels of ganglioside expression have been associated with increased EGF receptor autophosphorylation on tyrosine residues and increased EGF-stimulated cell proliferation.

Evidence also suggests that O-acetylated GM3 may increase the immunological activity of intact tumor cells. Gangliosides are potent pharmacological regulators of cell growth and cell differentiation. The direct addition of gangliosides to tissue culture medium causes growth inhibition by prolonging the G1 phase of the cell cycle and blocks cell proliferation in the presence of fibroblast growth factor and platelet derived growth factor.

Cow's colostrum is known to be rich in other nutritionally important and biologically active components, such as growth factors (e.g., which have been shown in numerous scientific studies to aid in healing and repair of the skin and microscopic tissue muscle) in antimicrobial agents (e.g. lactoferrin). ), minerals and vitamins Some of the major growth factors and other proteins found in cow colostrum are shown in Table 1 below:

Table 1

Growth factors IGF-1 50-2000 ng / ml IGF-2 200-600 ng / ml TGF-beta-1 18 ng / g TGF-beta-2 863 ng / ml Immunological-antimicrobial enzymes IgGl 52-87 g / l IgG2 1.6-2.1 g / l IgM 3.7-6.1 g / l Yoke 3.2 - 6.2 g / l lactoferrin 1.5-5 mg / ml lysozyme 0.14-0.7 mg / ml lactoperoxidase 11-45 mg / L

Hyperimmune colostrum can be obtained from a cow (bovine) in a manner similar to that described previously for producing HIM.

Arthritis is a degenerative condition that involves degeneration of the joints and connective tissues and is characterized by pain and swelling. Joint membranes (connective tissue) thicken and joints are tender.

There are many regulatory and growth factors present in the colostrum that provide anti-inflammatory protection. This protective effect is probably due, in part, to the eradication and / or neutralization of microbial pathogens associated with certain secondary diseases, such as certain forms of arthritis.

The conventional approach to the treatment of gastrointestinal disorders, inflammation and bone disease, relies on the potential use of pharmaceutical compositions with side effects.

The object of the present invention is to provide a composition which is capable of reducing or overcoming at least some of the problems described above or which provides a viable alternative. In particular, one object of the present invention may be to provide a nutritional composition comprising a combination of ingredients selected from a functional profile for use in the treatment of infectious diseases, including gastrointestinal disorders, inflammation and bone disease.

Other objects of the present invention may be apparent from the following description, which is given by way of example only.

The following is a summary of the invention.

In one aspect, the invention relates to a composition comprising a colostrum or a colostrum-derived product and a hyperimmune milk or hyperimmune milk-derived product in an amount sufficient to provide a combined spectrum of pathogen binding activity against a broad spectrum of pathogenic organisms.

Preferably, the composition further comprises ganglioside in an amount sufficient to provide antimicrobial binding activity.

Preferably, the composition further comprises other milk lipids and / or milk carbohydrates or milk carbohydrate derivatives.

In a further preferred embodiment of the invention, the composition further comprises calcium in an amount sufficient to provide the recommended daily amount required for healthy bone metabolism.

• ·

Preferably, the calcium is milk-derived calcium.

Preferably, the composition comprises from about 50% to about 95% (by weight) of colostrum, 5-50% HIM, and 0-10% milk lipids (e.g. gangliosides) and other ingredients, wherein the amount of HIM and milk lipid and other ingredients is not more than 50% of the formulation.

In a preferred embodiment of the invention, about 50-93% of the colostrum or colostrum-derived product comprises 5-45% of the hyperimmune milk or hyperimmune milk-derived product containing 2 to 4% of the ganglioside component and 0.1-1% of calcium.

Preferably, the colostrum or colostrum product is present in 60%, the HIM or HIM derived product in 35%, the ganglioside component in 3% and the calcium in 1.5%.

Preferably, the ganglioside-containing ingredient comprises an amount of ganglioside which provides a dose of 5 to 50 mg / day.

Preferably, the colostrum or colostrum-derived product is cow colostrum powder.

Preferably, the cow colostrum powder is coated with phospholipid.

Preferably, the colostrum is a hyperimmune colostrum.

Preferably the hyperimmune milk or hyperimmune milk-derived product is a hyperimmune cow's milk protein powder or skimmed milk powder.

Preferably, the ganglioside-containing ingredient is derived from cow's milk.

Preferably, the ganglioside may include GM 3 and GD 3 .

In another preferred embodiment of the invention, the composition includes, inter alia, about 65-70% milk colostrum protein powder, about 24-30% hyperimmune milk powder, about 2-4% ganglioside-containing ingredient and about 0.5% -1.5% milk calcium.

In another aspect, the present invention provides a dairy and / or colostrum-derived composition comprising colostrum or colostrum-derived product, hyperimmune milk or hyperimmune milk-derived product and gangliosides in an amount that provides a functionally balanced composition and increased anti-inflammatory activity.

Preferably, the composition contains about 50-93% colostrum or colostrum product, about 5-45% hyperimmune milk or hyperimmune milk product, and about 2-4% ganglioside-containing ingredient.

Preferably, the composition further comprises milk calcium. Preferably in a ratio of about 1.5%.

· ♦ · ··: ·

Preferably, the ganglioside-containing component contains gangliosides sufficient to provide a dose of 5 to 50 mg / day.

In another aspect, the invention provides a method of treating or preventing an infection-related disease, wherein the composition comprises a colostrum or a composition comprising a colostrum product and a hyperimmune milk or hyperimmune milk product in an amount sufficient to control a broad spectrum of pathogenic organisms. to provide a combined spectrum of pathogen binding activity.

Preferably, the composition further comprises gangliosides and calcium.

Preferably, the composition comprises about 55-95% colostrum or colostrum-derived product, 5-45% hyperimmune milk or hyperimmune milk-derived product, 2-4% ganglioside-containing ingredient and 0.1-1% calcium.

Preferably, the infection-related disease is H. pylori or Clostridium difficile-related disease.

Alternatively, the infection-related disease is an irritable bowel syndrome or disease or arthritic condition.

In another aspect, the invention relates to the use of a composition comprising a colostrum or a product of a colostrum and a product derived from hyperimmune milk or hyperimmune milk in the manufacture of a composition for the treatment of an infection.

Preferably, the colostrum or colostrum-derived product and the hyperimmune milk or hyperimmune milk-derived product (the composition) are present in an amount sufficient to provide a combined spectrum of pathogen-binding activity against a broad spectrum of pathogenic organisms.

Preferably, the composition further comprises gangliosides and calcium.

Preferably, the infection-related disease is H. pylori-related disease, irritable bowel syndrome or arthritic condition.

In another aspect, the invention relates to the use of a composition comprising a colostrum or a product of a colostrum and a product derived from hyperimmune milk or hyperimmune milk in the manufacture of a composition for the treatment of an inflammatory disease.

Preferably, the colostrum or colostrum-derived product and the hyperimmune milk or hyperimmune milk-derived product (composition) are present in an amount of: ··· · ·

- 7 which provides a functionally balanced formulation and increased anti-inflammatory activity.

Preferably, the composition further comprises gangliosides and calcium.

Preferably, the inflammatory disease is an arthritic condition.

In another aspect of the invention there is provided a composition essentially as described herein and with reference to the following examples.

Other aspects of the invention will be apparent from the following description which is given by way of example only.

The following is a brief description of the figures.

Figure 1 shows a comparison of the in vitro binding of different formulations to Candida albicans;

Figure 2 shows a comparison of the in vitro binding of different formulations to Salmonella typhimurium;

Figure 3 shows a comparison of the in vitro binding of different formulations to Klebsiella pneumoniae;

Figure 4 shows a comparison of the in vitro binding of different formulations to Clostridium difficile;

Figure 5 shows a comparison of the in vitro binding of different formulations to Escherichia coli 0157;

Figure 6 shows a comparison of the in vitro binding of different formulations to Helicobacter pylori;

Figure 7 shows a further comparison of the in vitro binding of different formulations to Candida albicans;

Figure 8 shows a further comparison of the in vitro binding of different formulations to Salmonella typhimurium;

9-11. Figure 5A shows a comparison with theoretical calculation.

The following is a detailed description of the invention.

It is a general object of the present invention to provide a composition for use in the treatment of a variety of infectious diseases, including gastrointestinal and joint disorders. The treatment may be prevention or response to the symptoms that have occurred.

It has been found that the combination of colostrum and HIM (or products derived therefrom) results in an effect over a wide range of bacterial infections beyond that observed when the individual components are used individually. For some bacteria, the effect is greater than even for the individual components; in other cases, the effect is the same or similar to using significantly less colostrum-HIM ingredients in the composition.

A particularly preferred ingredient of the composition is a ganglioside-containing ingredient. Gangliosides are milk lipids and the health benefits of such ingredients, in particular GM 3 or GD 3, have been previously described.

Other additives include calcium, especially calcium from milk and other milk lipids, phospholipids and milk carbohydrates, and derivatives thereof.

In a preferred embodiment, the composition may contain up to 50% (w / w) of HIM (with any other ingredients present) in equilibrium with colostrum or colostrum-derived products. Preferably, the amount of colostrum in the product is 50-95% (w / w), more preferably 60-80%, and most preferably 60-75%. HIM is present in 5-50%, more preferably 10-45%, and most preferably 15-40%. Of course, other combinations of concentration ranges may be used.

Colostrum was obtained from healthy, non-immunized, grazed cows which were skimmed, pasteurized and spray-dried to produce protein powder. The use of colostrum from hyperimmunized cows (i.e., hyperimmune colostrum) is also an optional solution. In another preferred embodiment of the present invention, the colostrum powder is enveloped with milk phospholipids, in particular, the envelope β-lipids include phosphatidylcholine, phosphatidylserine, phosphatidylethanolamine and sphingomilein.

Bovine colostrum has been shown to have specific binding activity against many pathogens including Candida albicans, E. coli 0157, Helicobacter pylori, Propionibacterium acnes, Kebsiella pneumonia, Staphylicoccus mutant, Streptococcus pyogenes, Streptoc , Yersinia enterocolitica, Staphylicoccus epidermitis, Salmonella enteriditis, Haemopilus influenzae, Campylobacter jejuni and Listeria monocytogenes.

In addition, bovine colostrum is rich in vitamins, minerals, growth factors (eg IgG) and immuno-antibacterial enzymes.

Hyperimmune colostrum can be used to maximize the amount of biologically functional antibodies and immunomodulators present in the colostrum.

Colostrum also contains a variety of components with anti-inflammatory properties, including lactoferrin, a proline-rich polypeptide, lysozyme, and growth factors (eg, IgG), some of which also have antimicrobial activity. In addition, the bovine colostrum for use in the composition of the invention has an immunomodulatory effect by blocking inflammatory cytokines such as TNF-α and IL-6.

Immune milk is obtained from cows that have been hyperimmunized with proprietary antigens and methods that result in increased amounts of unique dairy products containing biologically functional antibodies and immunomodulators.

Immunoglobulins in IIIM have been shown to specifically bind to the following pathogens: Pseudomonas aeruginosa, Aerobacter aerogenes, Haemophilus typhimurium, Streptococcus mitis, Proteus vulgaris, Shigella dysentocera, Streptococcus pneumoniae, Actinomyces, Actinomyces ., 3, 5, 8, 12, 18, 22).

It is known that these pathogens play a role in many diseases or physiological disorders including food poisoning, gastrointestinal ulcers, skin and lung infections, mouthwash, tooth decay and gum disease, surgical infections, respiratory diseases, and bowel disease.

The following is a list of typical pathogens and associated diseases. The composition of the invention may be used to treat and / or control such cases.

Table 1

pathogen Caused disease Candida albicans candidiasis, thrush E. coli 0147H7 food poisoning Clostridium difficile indigestion Enterobacter aerogenes Skin and lung infection. They also found species in the colon. Yersinia enerocolitica indigestion Proteus vulgaris Maybe a bowel disease Sheigella flexneri Possibly an indigestion Salmonella typhimurium food poisoning Bacteriodes thetaiomicronin They found species in the colon. Bacteriodes fragilis They found species in the colon.

Gangliosides, in particular the GM 3 and GD 3 described above, have been shown to have beneficial effects on the gut, brain, and cell growth and cell development. It is possible that their anti-adherence and antimicrobial activity (e.g. in E. coli and H. pylori, and various microbial toxins such as Shigra-toxm.) May further increase or complement the clinical benefits of colostrum combined with HIM.

The FLZSrt diagram (see Figure 7) shows that the ganglioside product added to the composition of the invention does not appear to show binding itself on the selected microorganisms. Gangliosides have antimicrobial activity but do not bind to the microorganism. In contrast, activity is understood to be an anti-adhesive effect (see Idota et al., Supra). Thus, the action of the ganglioside component should not exert its effect on the binding activity of HIM or colostrum. This suggests that the effect of the formulation is independent of the ganglioside product, indicating that the synergistic binding effect occurs between colostrum and HIM.

The following figures (9-11) show the binding effect that would be expected with a purely additive effect of the ingredients. 9-11. however, it is shown in Figures 1 to 4 that in fact a higher than expected binding effect is achieved, which underlines the synergistic effect of the combination of HIM and colostrum.

It is possible that the observed increased binding (as shown in the figures) of the HIM and colostrum preparation is due to the action of ganglioside. Such an effect would be very unexpected and in itself would be a synergistic effect. In this sense, a further aspect of the invention relates to the combination of HIM and colostrum (or derivative products) with a ganglioside.

In order to provide suitable antimicrobial binding activity (and potential synergy), the preferred concentration of gangliosides in the composition is sufficient to achieve a daily dose of 5 to 50 mg. The gangliosides are preferably present in the composition in an amount of about 0.0205%. The ganglioside-containing ingredient can thus be up to 10% of the composition, depending on the ganglioside concentration of the ingredient. More preferably, the amount of gangliosides in the composition is 2-4%.

The ganglioside product was prepared as a non-genetically modified product directly extracted from milk. The product (or ganglioside-containing ingredient) contains GM 3 and GD 3 gangliosides in concentrated form.

The composition may contain other lipids and carbohydrates. Examples of lipids include:

sphingomyelin, phosphatidylserine, phosphatidylcholine. Examples of carbohydrates are: galacto-, · · ·:

oligosaccharides, sialyl lactose, sialylated oligosaccharides. These examples are not intended to limit the scope of the invention.

The calcium used in the composition of the invention is also of milk origin. The preferred calcium content is about 0.1% to about 2% of the composition. More preferably, the calcium content is 0.1-1.5%.

The specific binding activity and complementary activity of colostrum and hyperimmune milk concentrates against gastrointestinal pathogens, which is further assisted by the sialic acid binding activity of gangliosides, means that the composition of the invention is more specifically directed against acute and chronic gastrointestinal disease. Examples of such diseases are gastric ulcer, duodenal ulcer, ulcerative colitis, Crohn's disease, chronic diverticulosis, irritable bowel syndrome, pseudomembranous colitis, antibiotic-associated diarrhea, and travel diarrhea.

By combining colostrum and hyperimmune milk in appropriate proportions, a product is produced which exhibits a broad spectrum of activity against pathogenic organisms, with expected and potentially unexpected clinical benefits. The bacterial (bacterial) effect of the individual components is expected, but the activity level of the combination is unexpected and provides therapeutic and cost benefits.

Typical key proportions of the main ingredients of the preparation are summarized in the following table:

Component Minimum% Maximum% colostrum 50 95 hyperimmune milk 5 50 ganglioside 0 10

The combined amount of HIM and other ingredients must not exceed 50% of the product. As is obvious, the (concentration) ranges are indicative only.

As shown in the examples and experiments carried out, the effects of treatment using the composition of the invention are significant. It is known that the individual components of the formulation (HIM and colostrum) have beneficial effects, but it is unexpected that a combination of these will show the efficacy shown herein. Accordingly, it is believed that there may be a synergistic interaction between the HIM and the colostrum component of the composition, either directly or indirectly.

- 12 Example 1

A test composition was prepared containing 70% colostrum milk protein powder, 24% hyperimmune milk powder, 4% ganglioside-containing ingredient, whey powder, lactose and 1.5% milk calcium.

Further details of the chemical composition of the resulting formulation are summarized in Table 2:

Table 2

Composition of the trial preparation

Component weight % protein (d.b.) 76.0% fat 2.5% lactose 12.0% ash 7.5% water 4.9% Immunoglobulin G As determined by HPLC protein G > 15% ganglioside 0.036% calcium 2:15% IGF-1 min. 500 + 50 ng / g szfingomilein min. 0.00325% phosphatidylcholine min. 0.0600% phosphatidylethanolamine min. 0.0350% phosphatidylserine min. 0.0075%

In vitro binding studies

Binding assays were performed with the test formulation, colostrum milk powder, skimmed milk powder and HIM on various bacterial and fungal pathogens including Candida albicans, Salmonella typhimurium, Helicobacter pylori, E. coli15, Velostella and Clostridium with pneumonia. The results are shown in Figures 1-8. 4A. In summary, the test composition exhibited a very high specific binding rate to the test species.

- 13 In vitro anti-inflammatory properties

The tight junction measurement procedure measures the degree of leakage of epithelial cells, and more specifically the monolayer cell border of kidney cells. It is normal for epithelium, such as the intestine or kidney, to have a tight barrier or a barrier. however, this barrier may in some cases be damaged, causing the epithelium to become permeable. Such a situation occurs during inflammation.

In the assay, cells are incubated with or without a test sample and then exposed to a permeation compound. Any increase in permeability is measured and activity is measured as a change from baseline obtained prior to exposure to the compound. The lower the unit of activity, the less cells become permeable and thus the protective effect of the sample is greater.

The activity of HIM in such a test was compared with the anti-inflammatory properties of various mouse models of inflammation and a good correlation was found. Thus, the tight junction assay is a good screening procedure for measuring the anti-inflammatory activity of milk samples.

In this assay, the test formulations were compared with HIM, bovine colostrum, and control. Each sample was diluted to 10% (w / v) with phosphate buffered saline and centrifuged for one hour to remove caseins. The whey fraction was tested in a tight junction measurement. MDCK cells were cultured to confluency with Transwell and serum was added at 10% for 48 hours. No whey was added to the controls. Transepithelial electrical resistance was measured across the monolayer before and one hour after exposure to EGTA. Each sample was quadrupled.

The results are shown in Table 3.

Table 3

Sample Activity (unit) Bovine colostrum -5 test Preparation -11 Hyperimmune milk -13 control 35

All samples showed significant protective effects when compared to the control. The activity of HIM was significantly higher than that of bovine colostrum. The test preparation

- 14 were statistically significantly better than bovine colostrum and only slightly less potent than HIM, despite the fact that the test formulation contained only 24% hyperimmune milk. It is clear that the test composition increased the protective effect of hyperimmune milk per unit volume. Growth is considered significant (significant).

In summary, the test composition of the present invention comprises a combination of components each having unique antimicrobial binding and / or anti-inflammatory activity, combined with unique and unexpected clinical benefits in a wide range of diseases including infectious diseases and, more specifically, gastrointestinal, bone disorders. Such advantages are unexpected results of the combination used.

In addition, the composition may contain sufficient amounts of calcium for the average daily requirement of human calcium intake, and include a wide variety of vitamins and minerals, and a balanced protein / carbohydrate mixture.

The composition is preferably used for the prophylaxis and treatment of disease, alone or in combination with a conventional drug.

Another typical chemical composition of the composition of the invention is shown in Table 4.

Component typically, % (w / w) protein (d.b.) 77 % fat 2 % lactose 13 % ash 7 % water 5 % Immunoglobulin-G as determined by HPLC-protein-G 17 IGF-1 min. 500 + 50 ng / g calcium 2.2 % ganglioside 0079 % szfingomilein 0:28 % phosphatidylcholine 0.0600 % phosphatidylethanolamine min. 0.0350 % phosphatidylserine min. 0.0075 %

- 15 »· .Ml · Μ

The formulations shown in Tables 2 and 4 are variations of formulations prepared with milk protein concentrate. One skilled in the art will recognize that variants of skimmed milk may also be used.

Example 2

1-8. Referring to FIGS. 6 to 9, a comparison of the test composition with the control (skimmed milk powder) and the two main components of the test composition is shown. The figures show the effects of in vitro binding of different samples to a number of pathogens.

As can be seen, the test composition has significant advantages over other samples. This is surprising since the test formulation contains significantly less colostrum and HIM than the corresponding reference samples.

Referring to Figure 7, the ganglioside sample shows little or no binding to the Candida albicans pathogen. This has been described previously.

Example 3

A pilot study was conducted with a gastroenterology clinic for abdominal disease and IDB (Cro / m disease and ulcerative colitis). Twenty-five patients who did not respond to current therapies were used. The duration of the examination was 6-8 weeks. The dose was 20 g twice daily. In more than 20% of cases, we have seen dramatic improvements. In more than 34%, it was clinically considered that therapeutic recovery was achieved after relapse of previous standard therapies.

Evaluation of symptoms before and after consumption of a composition of the invention containing 60% colostrum, 35% HIM, 3% ganglioside and 1.5% lactic calcium:

Before After - esophageal and lower abdominal pain - skin lesions - severe constipation or diarrhea - exhaustion - frequent bowel movements - pain - insomnia or lack of sleep - regular and normal bowel movement, descending frequently - normal sleep patterns - disappearance of pain - more energy, mood improvement - reduction in the need for other medications

• · · · ·

The present invention may be formulated in a tablet or capsule or as a powder for administration as a beverage. Depending on the product to be used for prophylaxis or treatment, and depending on the specific medical indication, the daily effective dose is expected to be from about 1 to about 40 g. For the treatment of gastrointestinal disorders, a preferred dosage regimen may be 10 to 30 g / day administered twice daily on an empty stomach. In the treatment of gastric ulcer, it is expected to be administered preferably with a mucolytic agent. Administration of the preparation may allow the dose of conventional anti-ulcer drugs to be reduced or omitted.

As reference herein is made to specific components or embodiments of the invention that are known to be equivalent, and through equivalent embodiments, these equivalent solutions are also part of the disclosure.

The invention has been described by way of examples and possible embodiments, but it is to be understood that modifications and improvements not departing from the scope of the invention and the spirit of the claims are also within the scope of the invention.

Claims (20)

    Claims
  1. A composition comprising colostrum or colostrum products and hyperimmune milk (HIM) or a product derived from hyperimmune milk in amounts sufficient to provide a combined spectrum of pathogen binding activity against a broad spectrum of pathogenic organisms.
  2. The composition of claim 1, wherein the ganglioside component is present in an amount sufficient for antimicrobial binding activity.
  3. The composition according to claim 1 or 2, further comprising milk lipids, phospholipids and / or milk carbohydrates or carbohydrate derivatives.
  4. 4. The composition of any one of claims 1 to 5, further comprising calcium in an amount sufficient to provide the recommended daily requirement for healthy bone.
  5. The composition of claim 4, wherein the calcium is dairy calcium.
  6. The composition according to any one of the preceding claims, wherein the composition comprises from about 50% to about 95% by weight of colostrum or colostrum-derived product; about 5-50% HIM or HIM-derived product; and about 0 to 10% ganglioside or other ingredient; wherein the amount of HIM or HIM-derived product and ganglioside or other ingredient does not exceed 50% of the composition.
  7. 7. The composition according to any one of claims 1 to 4, wherein the composition comprises about 50-93% colostrum or colostrum-derived product, 5-45% hyperimmune milk or hyperimmune milk-derived product, 2-4% ganglioside-containing ingredient and 0.1-1% calcium.
  8. 8. Referring to FIGS. A composition according to any one of claims 1 to 6, wherein the ganglioside-containing component comprises ganglioside sufficient to provide a daily dose of 5 to 50 mg.
  9. The composition of any preceding claim, wherein the colostrum is a hyperimmune colostrum.
  10. The composition according to any one of the preceding claims, wherein the colostrum or colostrum product is bovine colostrum powder.
  11. A composition according to any one of the preceding claims, wherein the colostrum powder is coated with a phospholipid.
  12. The composition according to any one of the preceding claims, wherein the hyperimmune milk or the product derived from the hyperimmune milk is bovine hyperimmune milk powder or skimmed milk powder.
  13. The composition according to any one of the preceding claims, wherein the phospholipid or ganglioside-containing ingredient is derived from cow's milk.
  14. 14. A 3-13. A composition according to any one of claims 1 to 6, wherein the ganglioside-containing component comprises GM 3 and / or GD 3 .
  15. 15. or 8-15. (if independent of claim 7), wherein the composition comprises about 65-70% colostrum milk powder, about 24-30% hyperimmune milk powder, about 2-4% ganglioside-containing ingredient and about 0.5-1.5% lactic calcium .
  16. 16. A milk and / or colostrum preparation comprising a colostrum or a colostrum-derived product, a hyperimmune milk or a product derived from a hyperimmune milk, and a ganglioside-containing Ingredient in a proportion sufficient to provide a functionally balanced composition and increased anti-inflammatory activity.
  17. The composition of claim 16, wherein the composition comprises about 50-93% colostrum or colostrum-derived product, about 5-45% hyperimmune milk or hyperimmune milk-derived product, and about 2-4% ganglioside-containing ingredient.
  18. The composition of claim 16 or 17, further comprising lactic calcium, preferably in a ratio of about 1.5%.
    - 18 · »· ····· * • · · ············
  19. 19. A composition according to any one of claims 1 to 6, wherein the ganglioside-containing ingredient may contain ganglioside for a daily dose of 5 to 5 mg.
    A composition comprising colostrum or colostrum-derived product and hyperimmune milk (HIM) or a product derived from hyperimmune milk in amounts sufficient to provide a combined spectrum of pathogen binding activity against a broad spectrum of pathogenic organisms for use in the treatment or prevention of an infection-related disease.
    The composition of claim 20, further comprising ganglioside and calcium.
    22. A composition according to claim 20 or 21 comprising about 50-95% colostrum or colostrum derived product, about 5-45% hyperimmune milk or hyperimmune milk derived product and about 2-4% ganglioside-containing ingredient.
    - 19th
    23. A 20-22. A composition according to any one of claims 1 to 6 for use in the treatment or prophylaxis of an infection associated with H. pylori.
    24. A 20-22. A composition according to any one of claims 1 to 6 for use in the treatment or prevention of an irritable bowel syndrome or arthritic condition as an infection-related disease.
    Use of a composition comprising colostrum or a product of colostrum and hyperimmune milk (HIM) or a product derived from hyperimmune milk in the manufacture of a composition for the treatment of an infection.
    The use of claim 25, wherein the colostrum or colostrum-derived product and the hyperimmune milk (HIM) or the product derived from the hyperimmune milk are present in amounts sufficient to provide a combined spectrum of pathogen binding activity against a broad spectrum of pathogenic organisms.
    The use according to claim 25 or 26, wherein the composition further comprises gangliosides and calcium.
    28. A 25-27. The use according to any one of claims 1 to 4, wherein the infection-related disease is H. pylori-related disease.
    29. A 25-27. Use according to any one of claims 1 to 4, wherein the infection-related disease is Clostridium difficile-related disease.
    The use of claim 29, wherein the infection-related disease is irritable bowel syndrome.
    31. Use of a composition comprising colostrum or a product of colostrum and hyperimmune milk (HIM) or a product derived from hyperimmune milk in the manufacture of a composition for the treatment of an inflammatory disease.
    Use according to claim 31, wherein the colostrum or colostrum-derived product and the hyperimmune milk (HIM) or the product derived from the hyperimmune milk are used in amounts sufficient to provide a combined spectrum of pathogen-binding activity against a broad spectrum of pathogenic organisms.
    Use according to claim 31 or 32, wherein the composition further comprises gangliosides and calcium.
    34. A 31-33. The use according to claims 1 to 4, wherein the inflammatory disease is an arthritic condition.
  20. - 20 35. A 25-34. The use according to any one of claims 1 to 4, wherein the colostrum is a hyperimmune colostrum.
HU0400589A 2000-11-15 2001-11-15 Colostrum-based composition HU0400589A3 (en)

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CN1299771C (en) 2007-02-14
EP1341554A4 (en) 2005-06-15
AU2424002A (en) 2002-05-27
US20040047856A1 (en) 2004-03-11
US20050220894A1 (en) 2005-10-06
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JP2004517067A (en) 2004-06-10

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