JPS60208919A - Method of obtaining transfer factor from first milk, transfer factor and use - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

DETAILED DESCRIPTION OF THE INVENTION BACKGROUND OF THE INVENTION Both breast cancer contains antibodies of the humoral immune system and cells known to function in the cellular immune system, including T cells, 1B cells and macrophages. (Watso
n + D −L * + 1980 + A u s
t a J - B io 1-8c1. 33:4
03”, Outerldge, P, M, and L
ee, e, S., 1981. Adv, Exp, Med,
& Biol, 137:513) The proportions and amounts of various antibodies and of various cell types vary between the milk and colostrum of a given species, and between different species (W & Biol, 137:513).
ataon, 1980;
dLee, 1981). The antibodies produced in colostrum are known to be small, while the various types of cells that are probably present in colostrum are less robust, even if only 1.
Even if you look at the pictures carefully, it is thought that immunity is only provided locally (Watson).

1980; Outerldge and Lee, 1
981).

Watson points out that there is still a possibility that 6-cell immune phenomena can be transmitted from mother to child by the transfer of lytic factors produced by lymphocytes, such as transfer factors.
Up until now, no one, including Mr. N, has reported on cell-mediated immune transmission using soluble products obtained from colostrum or colostrum cells, and the existence of transfer factors within 17E colostrum or colostrum cells. No one reported it. Conversely, a recent paper shows that colostrum does not have the desired number of natural killer cells (Kohl, S.

at ml, 1978. J,Cl1n,Lab,
Immunol.

1:221-224. Human Co1ostral
Cytotox1city% and colostrum or milk block the ability of broad spectrum substances to induce cellular immunity,
When given to animals or mixed with cells in vitro, it may actually suppress cell-mediated immunity by preventing normal peripheral blood lymphocytes or neutrophils from killing foreign cells (Ogra ,S,S.

and Ogra, P., 1. ．． 1978. J,Pedl
atr.

92:550-555'', Crago, SB, e.
tal,.

1981, CIn, Exp, Immunol, 45:3
86-392) have been pointed out. Furthermore, since confirmation of the amount of tolan in the current length has not been reported, such transfer factors exist in large amounts in colostrum, and as a result, this substance, which was previously rare and expensive, can be easily and inexpensively obtained. That was completely unexpected. Finally, 19
The presence of 72 bulb cells in the colostrum does not imply the presence of transfer factors. It is well known that serum and blood containing lymphocytes do not contain transfer factors unless the lymphocytes are stimulated by an antigen. Additionally, all literature related to transfer factors teaches that the transfer factor should be a product of Hertzian or inducer T cells. For colostrum to be effective as a source of transfer factors, the number of Hel,6-T cells must significantly exceed the number of suppressor T cells (as in peripheral blood), since suppressor A18 cells are This is because it is the generative power of a substance that is thought to cancel out the effect or action of a factor. It has been reported that the ratio of helper 79779 spheres to suppressor Nilin 6 spheres in colostrum is lower than that in peripheral blood, and therefore, in conclusion, the physiological role of 19779 spheres in colostrum is still unclear. It is difficult to predict” (Rlehie st al, 1982゜J, L
mmunol, 12-9-:1116-1119).

It is known that it is possible to stimulate or transmit the &lli ri"rv immune response and that the transmission can be realized in different languages (Flu denberg, H.
H,, W son.

G,B,Goust,JlM,,Nekam,ni,,a
ndSmlth, C.L., 1980. Quantity n T
bymus-m-.

Thymlc Ilormones nnd T Ly
mphoc)-tea.

Δ1uti, F., and Wigzell, H.
ads,.

London, Academic Press, p. 3
91;W118011. G, B, and F'uden
berg, 11.11. .

1983, I++ununology Today 4
:157”.

Kleslus, I', II,, F'udenberg
, 11.11. .

5rnlth, C6L, 1980. Co+np, Im
munol.

Mlcroblol, Infec, INs, 3:247
).

It is also known that transfer factors can be obtained from blood cells such as serum leukocytes or lymphocytes, but these transfer factor sources are expensive and time consuming. leukocytes [eukophoresis] or killing of the animal, and requires a tedious extraction process (Wllson
and Fudenberg, 1983;
ua etal,, 1980”, Klesius, P.
H., and Kristensen, F., 1977, C.
lIn.

Immunol, Immunopathol, 7*24
0”.

Wilaon, G.B., and Fudenberg,
H, H,.

1981, Lymphoklnss 4:107)0
The yield of transfer factor is low considering the effort involved and the amount of tissue used. Furthermore, it is also known that various tissues or cells can be obtained by culturing the cells or alternatively with antigens or organisms that cause the cells to release TF into the medium (Wson, G., et al.
B., ,FL Andenberg, H. II.

Paddock,G,V, ,Tsang,ni,Y,,
Wlliams.

A. M. and Floyd, E., 1983. in
Immunobiology of Transfer
Factor.

Kirkpatrick, C.H., Burgsr, D.
,R.

and Lawrence@, H, S,, ed@,, N@
w York.

Academic Press, p. 331) (,) Transfer factor is a transfer factor source and Fudanberg, 1983: Wilso
and Fudenberg, 1981), and can be obtained by culturing specific for a given antigen (!
(Wl 1 so nat al., 1983) is also known. Finally, it is also known that transfer factors specific for a given antigen can be derived by successive transfers of this factor from an immunized subject to another (Kirkpatrlek, C.).
nd 8m1th.

T', 1976, Cs11. Inmunol,
27:323).

SUMMARY OF THE INVENTION The present invention provides a method for inexpensively obtaining a virtually infinite stitch transfer factor (TF) from a readily available source. By the method of the present invention, excreted TF specifically specific for a certain antigen is secreted from the mammary glands of a suitable lactating mammal, such as the colostrum or milk of a cow having immunity to the antigen. Substances that interfere with the effects of TF are removed, and as a result, TF
can be obtained by collecting them under suitable conditions such that they are obtained. It is preferable to use colostrum as a source of TF (it is preferable to use colostrum, which contains cells, cell debris, casein, immunoglobulins, and other undesirable substances from the colostrum that contains TF). Processed to separate.

If desired, it is also possible to further concentrate and/or purify the transfer factor. Separation, concentration, and purification methods that may be used include one or more of centrifugation, extraction, precipitation, ultrafiltration, dialysis, chromatography, and lyophilization.

In other cases, intracellular transfer factors may be derived from isolated colostrum cells by culture release or cell rupture. In addition to colostrum and milk, transfer factors can also be obtained from mammary tissue of suitable lactating 11m mammals.

The transfer factors prepared as described above may be used in edible compositions or alternatively in pharmaceutical or veterinary compositions for the prevention or treatment of diseases associated with antigens for which the TF itself is specific. may be contained in TF can be used to confer immunity against diseases associated with antigens for which it is specific, such as Mycobacterium bovis (
Mycobaeterlum bovls), Cooccidioides immitis (Coeeldloides 1)
Herpes simplex virus containing mrnit1m, human j>・, Ea
l<#1 Zevirus, bovine rhinobronchitis virus, bovine parainfluenza virus, Newcastle disease virus, Marek's disease virus, infectious bronchitis virus, laryngotracheitis virus, protozoa, or antigens related to cancer, etc. .

3. Detailed Description of the Invention In the following description, at least three types of transfer factors (TF) will be mentioned. The first type of excreted transfer factors (TFs) are released from TF-containing cells and can be collected from the extracellular fluid. The second type of pre-discharge (prs-excr
eted) TF (TFpre) is thought to occur inside cells or on the cell surface, and is released as TFe after structural changes. The third type of internal
) TF (TFl) is also found inside or on the cell surface, and the chemical structure of this TF is believed to be different from both TFe and TFpre. TFpr
e and TFl are herein referred to as intracellular (cell as
social@d) Also called TF'. The three types of TF are detailed below.

Antigen-specific efflux transfer factors (TFs)
In this method, substances secreted from the mammary gland of a suitable mammal during lactation are subjected to suitable conditions such that substances that interfere with the effect of transfer factors, that is, their function of imparting cellular immunity, are removed and, as a result, transfer factors are obtained. can be obtained by collecting under. Colostrum is a particularly rich source of transfer factors. TFs can also be obtained from milk, but the degree of TFed in milk is more variable than in colostrum. Colostrum is therefore currently preferred as the material for obtaining TFe. By using colostrum or whey in this way, a large amount of TFe can be easily obtained at low cost. In other cases, mammary gland tissue may be used as a source of transfer factor.

Suitable mammals for use in the present invention are those that have immunity to the antigen, such as humans, cows, or goats. Such mammals can be determined by screening to confirm the presence of immunity as described above, or alternatively, the mammal can be immunized by injection with antigen-specific antibodies or transfer factors, or by exposure to the antigen, prior to the start of lactation. can be done. Transfer factors obtained from the above mammals are specific for a given antigen.

(hereinafter referred to as 1.゛Kinpaku) Said suitable mammal may be suitably immunized by conventional techniques known to those skilled in the art, such as by intraperitoneal, subcutaneous or intramuscular injection of a suitable antigen. After immunization, sufficient time must be allowed for the mammal to react to the immunogen (antigen), usually at least about 1 to 2 weeks, before the material, such as colostrum or milk, is collected. - Typically, if the suitable animal is a cow, the immunogen is injected between the fifth and seventh month of gestation to confer immunity. In one method, a primary injection is given to cows between 6 and a half to 7 months of gestation, followed by a secondary (booster) injection 3 to 4 weeks later. As a result, a period of one to one and a half months is required before delivery and subsequent collection of colostrum, etc. An alternative practice is to give the first injection during the 5th month of the IM, followed by the second injection 3-4 weeks later, giving the cow another month to 1.5 months to react to the immunogen before calving. You may leave it behind and perform the third injection. T if the animal has been given booster immunizations according to an annual schedule.
F-containing material can be collected after secondary injections, usually throughout the year.

Commercially available veterinary vaccines are administered to mammals (rhinotus) according to the usual doses and protocols used in routine vaccinations.
racheitia virus) vaccine (Charles City, Iowa - 18alsbury La.
boratories Inc.) or bovine parainfluenza virus (Salsbury Laboratories Inc.) or bovine parainfluenza virus (Salsbury Laboratories Inc.)
vaccines) can be appropriately immunized according to the same methods and dosages as for conventional vaccination. Mycobacterium bovi
s), for example Cl1n, Irrm
unol, and Irrmuno-pathol.

(1977) 8:238-246.
sius P, )1. and Fudenberg,
H, H.

It can be suitably carried out using the following method. Immunization of cattle against Newcastle Disease Virus, Marek's Disease Virus, and Infectious Trachea was carried out by the manufacturer (Salsbury Labora).
poultry vaccines such as those obtained from
This can be accomplished by injecting three vials into a cow.

Each vial contains vaccine for approximately 1.000 chickens. Alternatively, vaccines prepared by methods known to those skilled in the art may be injected into a suitable mammal as described above. For example, in the case of cattle, appropriate immunity can be given by injecting 3.5 to 71Q spherulin 1 to 3 times each time. This spherulin is obtained by washing inactivated spherules of C. imititis (C, Irn+nitis) with saline solution, for example, 1 c of physiological saline.
This is a preparation consisting of formalin and preserved at a concentration corresponding to 7 da dry inactivated microspheres per c.

Cattle can also be immunized by injection with live attenuated herpes simplex virus of 107-10' PSU.

It will be apparent to those skilled in the art that the precise amount of antigenic material to be injected will depend on the size and reactivity of the cow or other animal being immunized. The potency of the transfer factor of the material collected or a fraction of the material can be determined according to the assays described above (CIin, Irrmunol, Ir
Wilson, G., Rwnunopathol, 23:478 (1982).

B., Metcalf, J.F., & Fuden.
berg, H.H.

method, as well as G.B. on June 16, 1983.

Wilson and H. H. Fudenberg, co-pending U.S. Patent Application No. 650,498.”
Use of in vitro As5ay Te
chnipexT.

Measure Parameters Relate
d To C11nical Applications
of Transfer Facton Thera
py').

The TFa degree of the collected material (expressed in units of potency PU as measured by the assay) depends inter alia on the responsiveness of the cough-eligible animals to the immunization and on the time of material collection relative to parturition.

Colostrum or milk obtained from weanling animals with adequate lactation can be used directly as a lactation composition and the like.

The collected material may then be subjected to treatments such as ultrafiltration or dialysis to recover the transfer factor.

Leukocytes which have not yet released TF with a given antigen specificity become capable of releasing said TF when their incubation is carried out with an antigen that generates incubation-released TFe (IR-TF). Kirk patrick on this.

Burger, C.H., and Lawrence, D.R.
e, It, 8゜% Irrrnunobiolo
gy of Transfer Factor (198
3rd year) New York Academic press
.

WjlSOn, G as described in Pp 331-336
-B'-+Fudenberg, H, H, Paddo
ck, G, V,, Tsang.

K., Y., Williams, A.
M., and Floyd, E.

Please refer to the paper.

In one embodiment, colostrum is collected and processed to substantially remove cells, cell debris, casein, and fat.

The removed cells were removed using IA/1lson et al.'s protocol, 1
TFe may be contacted with the antigen under appropriate conditions to release TFe, according to the US Patent No. 983. This TFe may then be concentrated or purified, and the concentrated or purified TFe may be sterilized. Sterilization in this and other practices is carried out using a commercially available filter sterilization unit, e.g.
This can be done successfully using the gene unit.

Treatment to substantially remove cells, cell debris, casein and fat may include low speed centrifugation (e.g. ioo to 12,000 g) for e.g. 5 minutes to 1 hour, followed by further e.g. 10 minutes to 1 hour. High speed centrifugation (e.g. 10,
000 to 11O,000&). Low speed centrifugation in this and other implementations includes not only conventional centrifugation, but also conventional cream separator processing.

In one example, pre- and postpartum colostrum (or milk) is collected at approximately 380p (100-200C) for 15 minutes at approximately 4-37°C.
00 g) at low speed.

If cells are to be harvested for subsequent use, it is better to process at lower speeds. Skim the fat from the surface and separate the remaining suspended material from the pelleted cells by decanting. These pelleted cells are stored to obtain a dialysable leukocyte extract (DLE), ie intracellular TF as described below or incubation released (IR) TF as described above. Then, about 25,000 g (10,000 to 110,000
g) High-speed centrifugation. Processing with lower g-forces may be used, but the time required may be longer and the purity of the processed material may be poorer. Centrifugation can also be carried out using only higher g-forces, but such treatment makes it difficult to recover viable cells or cells that are less contaminated with fat and/or casein. The residual fat is skimmed completely from the surface of the material and the residual suspended material (colostrum whey) is separated from the casein and cell debris by decantation. Alternatively, following standard procedures CaCQ2
Casein may be precipitated by adding and renin to the slow-processing suspended material, or by acidifying (pn 4-5) the suspended material, and the precipitate being removed by filtration or centrifugation.

(Schultze, H.E., and Herernan
s J, F., Molecular Biolo
gy or Human Proteins (1966
), Amsterdam, El 5evierBio
medical press Volume 1, pp? 32-
847: U.S. Pat. No. 4,051,23, issued September 27, 1977). Casein is first of all CaCQ 25
Precipitation may be carried out by successive precipitation processes, such as precipitation by diluting and addition of renin, followed by dialysis of the whey, followed by further acidification of the whey. The resulting colostrum whey transfer factor may be sterilized by t-filtration or other techniques, such as passing through a water sterilizer (Uv), the efficacy of which is determined by the techniques described above.
Wilson et al., 1982), but may be further processed. Administration may be by oral administration, topical administration or injection.

Alternatively, the colostrum can be subjected to low speed centrifugation as described above, followed by the addition of an appropriate amount of an agent that substantially transforms the immunoglobulins. In this method, the pH of colostrum whey is adjusted to approximately pH 5 with 0.1 volume of 3M sodium acetate.
The colostrum whey transfer factor can then be precipitated by ethanol precipitation at 0-4°C or -20°C (up to 2 volumes ethanol) and -20°C (4 volumes ethanol).

As previously thought, the interface is mixed 1] A
There is no need to remember (Klesius, P.
H.

and Fudenberg, H,H-,CIin-Cl
1n-Irr+I+rmunopathoL 8:
238, 1977; dated December 25, 1979 x
le/5ius, P, H.

and U.S. Pat. No. 4,180,627 to Fudenberg, H.H.). The aqueous and ethanol phases can be mixed immediately. Approximately 12 hours after cooling for 1 hour to overnight
．． The transfer factor precipitate may be recovered by centrifugation at 000 g (>10,000-20,000 g). 0.5 volumes of ethanol are added sequentially to the suspended material in several steps, followed by cooling as described above. and centrifugation can facilitate the fractionation of colostrum whey transfer factor. In summary, purification can be carried out by ethanol precipitation and various q parameters can be constantly varied [e.g. ionic strength, pIJ % temperature, ratio of ethanol to water added at each step, concentration of nucleic acids and proteins (transfer RNA can even be added as an inert carrier material to precipitate the transfer factor in dilute solution)].

By varying these IQ parameters, it was found that for a fixed ethanol to water ratio, the transfer factor could be transferred from the precipitate to the suspension depending on the conditions used in a given purification process.

Continuous fractionation using other known water-miscible solvents such as imprononol, t-butanol or acetone may be used to remove unwanted contaminants from the transfer factor. Peptide and nucleic acid precipitation reagents known to those skilled in the art, such as alcohol, ketone and polyethylene glycol removal, may also be used.

In another implementation, the collected material, such as colostrum, is subjected to low speed centrifugation as described above and then processed by ultrafiltration or dialysis. This type of method uses known molecular blocking methods, e.g.
Transfer factors can be separated from larger molecules using conventional dialysis membranes or filters with a molecular weight cutoff of .,000. This dialysis or isopronoq
Organic solvents such as alcohol are compatible with the filter or membrane and can be separated from smaller molecules using conventional dialysis membranes or filters with, for example, 1,000 molecular weight cutoff.

The transfer factor obtained by any of the aforementioned methods may be subjected to concentration and/or purification, for example by ultraviolet filtration or freeze drying or both, to further concentrate and/or purify the concentrated or purified transfer factor. This is done after carrying out the process to do so.

The following operational steps can also be added to improve the quality of the product in terms of concentration, potency, stability and degree of contaminant removal.

1. Lyophilize the colostrum whey transfer factor and store it dry for later use, and/or in pyrogen-free sterile water, saline, or any other fluid suitable for injection or oral administration. Can be dissolved.

2. Colostrum whey transfer factor can be extracted sequentially with phenol and ether (to remove residual phenol) at room temperature. Other known solvents used for protein denaturation and removal or nucleic acid removal, such as C1
(CQ!l or butano reverse phase (reverse ph
may be further purified by chromatography such as Sephadex, Sephadex, etc.; electrophoretic techniques such as acrylamide gels; or immunological techniques such as antigen binding (paddock, G, V, .
Wilson, G., B.

Williams, A., M., and Fudenb.
erg, H, H.

: Inmuaom! Logy and Tranaf
cr Factor (Kirk Patrmck, C
,H., ,Burger, D.R.

and Lawrence, H.S., eds.) New York.

Academic press, p. 51 (19
Wilson et al.: P, 31 (1983)]
.

As mentioned above, colostrum is preferred as a transfer factor source, but milk can be used instead of colostrum in the various cold flow methods of the present invention. Transfer factor can be obtained in a similar manner when milk is used instead of colostrum.

Thus, by treating milk in the manner described above, cells, cell debris, casein and fat may be substantially removed.

Cells removed from milk may also be contacted with antigen under appropriate conditions to release transfer factors. Furthermore, the cells can be removed, the transfer factor concentrated or purified, and then sterilized. These cells may be lysed to obtain intracellular TF.

These antigens include microorganisms such as bacteria, fungi, protozoa, rickettsia, mycoplasma, or viruses associated with diseases of other animals such as poultry, such as humans, lower animals, or chickens, or those derived from such microorganisms. is appropriate.

(Left below) Diseases of birds include fowlpox, chickenpox, dorsalis encephalomyelitis, infectious bursal disease (bursal dlsease),
viral arthritis, mycoplasma, gallisebuticum,
synovial fluid mycoplasma (f'T)ycoplasma
Newcastle disease, Marek's disease, infectious bronchitis, and avian laryngobronchitis.

Mammal diseases include foot-and-foot disease; rinderpest; bovine viral diarrhea; infectious gastroenteritis; African swine fever (Afrlc).
swine dysentery; rabies: equine infectious anemia; influenza; viral arthritis and viral rhinopneumonia; swine influenza; mycoplasma pneumonia
hyponeumonlae); donkey infectious anemia; canine distemper; infectious hepatitis and herpesvirus; burbovirus; coccidiosis species; lung parasite species; ascarls; salmonella; Pyorrhea: bovine rhinobronchitis; bovine rose influenza; and mycobacterium bovis
s) Human diseases include fungal diseases such as mucocutaneous candidiasis, vaginal candidiasis, histoplasmosis, and coccidioidomycosis; mycobacterial diseases such as tuberculosis, leprosy, Mycobacterium falcitum, and Mycobacterium s). Bacterium intracellularis; examples of protozoal diseases include Plasmodium vivax, Trypanosoma gambiae, Trypanosoma rhodesia, Pneumodystis carinii, Leishmania tropicalis, and Pediatricia; examples of neuroviral immune diseases Multiple sclerosis and Guillain-Barre syndrome; cancer example is osteosarcoma (O6sterosarcoma)
+ Lung cancer, Gravitz tumor, nasopharyngeal carcinoma, melanoma, alveolar carcinoma, renal cell carcinoma, epidermal dysplasia verrucous, and other cancers, especially cancers considered to be prevalent; autoimmune diseases, such as chronic discs IJ) Made-Des, Patchett syndrome; nematode examples are Ascaris canis and Bancroft heartworm; flatworm examples are Taenlasollum and hydatid; thoracic fluke example is Schistosoma mansoni; virus example is B
N-hepatitis, eczema vaccinalis, variola virus, herpesvirus, adenovirus, babobavirus, picornavirus, rhinovirus, togavirus, bunyavirus (B
unya vlruses), reovirus, orthomyxoviruses and varamyxoviruses including mumps, and rhabdoviruses.
, Retro Tile/C (Retrovlruses)
, arenaviruses, coronaviruses and hybrid viruses, such as chronic infectious neuroinhibitory agents, and other diseases, such as equine matoid arthritis; asthma; bacterial infections, chlamydia, mycoplasma and rickettsiae; or prions (ρr).
lon) There are related diseases.

Another method of the invention provides antigen-specific intracellular transfer factors. In this method, secretions from the mammary glands of suitable lactating animals as described above are collected, whole cells are collected from the collection, and substances that interfere with the efficacy of the transfer factor are removed (all the collected cells are collected under appropriate conditions). is processed to obtain the transfer factor.

In one embodiment of the whole cell treatment, the cells are disrupted by methods such as freeze-thaw lysis or sonication to release transfer factors, and the transfer factors are recovered from the disrupted cells. The cell disruption process may be repeated to ensure complete destruction. The transfer factor released from the destroyed cells can be recovered by known methods, such as centrifugation, fractional precipitation, ultrafiltration, and dialysis (eg, DLE). The resulting transfer factor may be purified or concentrated into noodle strings by similarly known methods, such as freeze-drying, extraction, chromatography, and the like. Additionally, the concentrated or purified transfer factor may be sterilized. This method yields 44+ different intracellular transfer factors for a wide variety of antigens. For example, intracellular transfer factors specific for M. bovls can be obtained in this manner. As one example, a bovine-derived intracellular transfer factor specific for μbOV l s is obtained from a harvest of counts from appropriate lactating cows.

As described above, by using the method of the present invention, transfer factors specific to a wide variety of antigens can be obtained. For example, C
occldioldes lmnltls-specific bovine transfer factor, C11nrnltls-specific TFe, and C,lrrmltls-specific Kushiyume TF
Eri contains TFe specific to herpes simplex virus and bovine T.
It can be obtained in the present invention similarly to Fe. Similarly,
Bovine rhinotracheitis virus, bovine rose influenza virus, Newcastle disease virus, Marek's disease virus,
Infectious bronchitis virus.

Or bird laryngotrachea! Transfer factors containing TFe specific for inflammatory viruses are also obtained.

In one embodiment, bovine transfer factor and TFe with the specificity described above can be obtained using harvests from suitable lactating cows. Using the purification method described in the text, till 81! TF can be easily obtained.

In summary, TF and intracellular transfer factor can be obtained by the above-mentioned method, such as cell disruption treatment or incubation release treatment of colostrum cells or breast cells.

Since the transfer factor or transfer factor mixture can be used to obtain it in a homogeneous state, this transfer factor may be used as a health food or as a food supplement or food additive to greatly enhance immunity against diseases. Good too. Accordingly, one embodiment of the invention includes an edible composition comprising a transfer factor obtained using one or more of the various methods of the invention and a suitable edible carrier.

Since transfer factors can be obtained in high yield and in pure form, they can be used in humans and non-human animals (e.g. livestock, poultry, pets such as dogs or cats) to immunize against the transfer factors. obtain. It is known to those skilled in the art that a composition containing a transfer factor capable of conferring immunity in a specimen can be used as a therapeutic or preventive agent for a disease associated with an antigen specific to the transfer factor. It should be obvious. Such a medicament or veterinary medicament contains an effective immunizing amount (a dose that confers effective immunity) of a transfer factor obtained using one or more of the various methods of the invention, and at the same time Contains a suitable pharmaceutical or veterinary carrier. Many class 8Ii carriers are known in the art. The present invention provides one example of M, bo
Vls or veterinary agents that immunize cattle against herpes simplex or bovine influenza virus. An example also includes veterinary agents that provide immunity to birds, such as chickens, against Newcastle disease virus, Marek's disease, infectious bronchitis or avian laryngobronchitis. The present invention further provides Coccl o1des Inmlt Is,
Includes agents that immunize human subjects against pathogenic agents such as herpes simplex and human mumps virus. Such compositions contain an effective immunizing amount of a transfer factor specific for the antigen associated with the disease, as well as a suitable veterinary drug or pharmaceutical carrier. Suitable carriers may be selected from a large number of carriers known for use in other veterinary drugs or pharmaceuticals.

Transfer factor potency of substances used in such agents can be quantified using leukocyte migration inhibition (LMI) assays. The assay consists of G,B,Wlls
pn, J.F., Metcalf and H.H., Fude.
nba rg.

lta 82, CI In, Irrmunol
, lrrmunopathol.

23:478 and G, B, WI l5on and H, H
, Fudenberg.

1981, Lymph Oklnes Sat: 107. This method allows one to determine the number of standard potency units (pu) of transfer factor in a sample. The effective immunizing dose of Transfer 7'1 is approximately 1-40% of the body weight of the animal or human specimen.
00 PU/kg preferably about 10-400 PU/kg
It's an illusion. In order to obtain a clinical effect, i.e., to prevent or treat diseases related to TF and specific antigens, it is necessary to use specimens with high antigen titers (e.g., those with advanced microbial invasion or tumor masses). A relatively high dose within the above dose range is required for specimens that are hypertrophic) or not in good general health.
It will be readily understood by those skilled in the art that a relatively low dose within the above dosage range is sufficient to protect a specimen in relatively good general health from infection with disease-associated antigens6. Furthermore, methods of immunizing humans or subhuman animals are provided. In the method, the transfer factor obtained by the method of the invention is administered to humans or lower animals in an effective immunizing amount. Suitable administration methods for transfer factors include oral administration, topical administration, or injection, and repeated administration may be used. 1
According to one embodiment, a cow may be immunized against M, bovls by administering to the cow an effective immunizing dose of a different intracellular transfer factor.

Similarly, for example to immunize cows against herpes simplex virus, bovine rhinotracheophilitis virus or bovine rose influenza virus.

T Fe specific for herpes simplex virus, transfer factor specific for bovine rhinotracheitis virus, or transfer factor specific for bovine rose influenza virus are each administered to cows in effective immunizing doses. For example, Newcastle disease virus, Marek's disease virus,
In order to make chickens immune to infectious bronchitis virus or avian laryngobronchitis virus, an effective immunizing dose of transfer factors specific to the respective viral antigens may be administered to the IJ of chickens. Furthermore,
To immunize a human specimen against the herpes simplex virus or the human mumps virus, C, Irrmltls K-specific bovine transfer factor, TFe specific for the herpes simplex virus, and human mumps virus. Virus-specific bovine transfer factors may each be administered to the specimen in an effective immunizing amount.

As mentioned above, the results of research on human, donkey, and bovine TF revealed that TF has three structural forms that differ in antigen specificity as described above.

Two of them are structural forms of TF that exist between cells or on the surface of immune lymphocytes, and the remaining one is in vitro for a predetermined period with or without antigen.
T excreted (secreted) from incubated immune cells
(IR-TF) (Wllson and F
Udenberg, 1983); (Wllson
etc., lrrmunoblogology ozTrans
ferFactor, 1983. p, 331) o For clarity, each of the three structural forms will hereinafter be referred to as TFI (intercellular TF, conventionally designated TF7), TF, .

(Pre-efflux TF, conventionally designated as phosphorylated TF5) and TFe (Excretory TF released from immune lymphocytes, or IRTF, conventionally designated as dephosphorylated TF5)
It is designated as. In order to know which forms of TF are present in the whey of colostrum and which forms of TF are present in colostrum cells, their physiochemical and structural characteristics are necessary. It is necessary to inspect the T' obtained from each of the colostrum whey and colostrum cells was found to be present in the aqueous phase after two-step phenol-ether extraction;
Ethanol precipitation was possible. Colostrum whey and cellular TF therefore exhibited similar effects to IRTF and DIETF from donkey, human and bovine lymph nodes or peripheral blood leukocytes. Even when the TF-containing substance was fractionated by a method such as cellulose TLC, the TF activity did not decrease at all.

The structure of TF in colostrum whey is closely related to the known structure of IRTF, and colostrum TF prepared by freezing and thawing colostrum cells has at least one of the predicted structures of intercellular TF. Contains a considerable amount.

Structural relationships can be estimated from the data in Table I and the simple block diagram model below6 (this is a discussion of a simple model that fits the existing data, and detailed structures that exclude other unknown molecular structures) (will not be considered).

; The digits in the formula represent oligoribonucleotide moieties. Furthermore, 3' and 5' in the formula indicate the 3'(2') and 5' directions, and N indicates a small number of unknown nucleotides.

In N, TFe and pre have at least one internal purine that is susceptible to becoming guanosine (G), and TFI has at least one internal pyrimidine (PV).

, P indicates an external phosphate that is easily removed by phosphatase. NΔbe indicates the carboxyl terminus, respectively. The bond joining the peptide and oligoribonucleotide is unknown.

It is to be understood that the above model is an exemplary model and does not exclude other molecular moieties that may later be found to be part of the TF structure.

In summary, various degrading enzymes (nucleases, ribonucleases, phosphatases, peptidases, and phosphogesterases) were used to determine whether DingF activity was destroyed by a given enzyme.

Removal of activity also includes structural inhibition of the species comprising the TF molecule. The data obtained establish the existence of a basic ribonucleotide structure analogous to the previously deduced structure of core TF. In other words, one? peptide (free carboxyl terminus, i.e. the activity is degraded by carboxypeptidase 8), and the peptide is at the N terminus (i.e. the activity is not degraded by the leucine amino pegtidase).
The presence of an elementary ribonucleoptide structure that is joined at the 5' end (i.e., the active is not degraded by the snake venom phosphodiesterase) prove

There are three basic molecular structures for TF activity. In structure A, internal guanosine is present, i.e. the activity is TI
(degraded by RNase), 21, there is no phosphate at the aF end. Structure B has an internal purine that is susceptible to guanosine and at the same time has a phosphate at the 21 and 31 ends (i.e. the activity is degraded by snake venom phosphogesterase only when the phosphate is removed by alkaline phosphatase). do). Structure C has an internal pyrimidine (activity is degraded by RNase A)
, 2' and 3' ends do not have phosphates, but do have phosphates, which are easily removed by bacterial alkaline phosphatase, which can attach to the peptide moiety. The structure AC efflux TF; TFe) is found in colostrum whey. Also, T released by the cells after incubation
F is also a form of structure A. Structure B (TF before discharge: TF,
. ) and C (internal TF: TFI) are found inside cells or on the cell surface. TF moieties shown in structures A, B, and C are all capable of conferring antigen-specific cell-mediated immunity. Cellulose TLC
(Methanol:HCI:H,0/70:20:1
The mobility of structure B on 0) is approximately equal to that of guanosine, and the mobility of structures A and C is approximately equal to that of 2' (3 monophosphate uridine).

(Left below) Table! 1, P1 nuclease --- ITIRNase --- + &RNase A + 10 - 5, Bacterial alkaline phosphatase (BAP) + + - aSV+BAP --- 7. Acid phosphatase (AP) 10 + -- & phosphogesterase ( 5p) + + + 9, AP + SP + + - 10, Pronase - - - 11, Carboxypeptidase A - - 1 & Quiquiaminopeptidase + + + The decrease in activity after enzyme treatment is indicated by (-). Activity after enzyme treatment No change is indicated by (→).

Colostrum whey A used in Test) A was purified using phenol ether extraction, ethanol precipitation, and cellulose TLC.

TF, e, and TF used in Test) B and C include those collected from sources other than colostrum for comparison in previous tests by the applicant.

(See 1 below) 叉-M-father-in-law The following antigens were used in the following examples.

Bovine rhinotracheitis virus, Harek's disease
Virus, Newcastle disease
s disease) virus, infectious bronchitis (infectious bronchitis)
fectious bronchitis) virus,
avian laryngotracheitis (laryngotracl+eiti)
s) Virus, bovine parainfluenza (parain
fluenza) virus.

All of these are from 5alsbury Laboratory.
es, Inc., Cbarles C1ty, Iowa
more available. The aforementioned small ball is Llniversi
Ty of California, Naval Bi
SciencesLaboratory, Naval
5upply Center, Oakland.

California, Dr., 11. B.Levin
Obtained from e. herpes simple
ex) virus (viable attenuated 11sV-1 as described above)
, 5train 35) is Llniversity o
f8 to abaIIla CoCo11e of Med
icine, Department of Hicrob
iology and Ismunobiology,
Medical Science Buyilding,
Mobile, ^Iabaia, Associate Professor 1 (, ^.

Obtained from Lausch. PP low B, PPD-F
, PPD-H and PPD-1 are 5tatens Se
rum Ins mouth tute, C0pella(J
en.

From Denmark (Coccidioides i+
uiLis antigen). The human mumps virus is Li1lv.

Obtained from 8evkeley, California. Commercially available Niso 1~ri is s, p, mouth, 1latcber
y, 5 outb Carolina, and sp^
``^su4;N is 5PAF8, Book I 1c, obtained from IC
0 Organic solvents and chemicals such as aretone, ethanol, ether, isopropanol and phenol are all of reagellt grade or above, ^1dricl+ Chemical Co.
Hilwaukee.

Available from Wisconsin.

The centrifuge used in the following examples *1 machine was 5orva I
I model RC2B centrifuge 111 [1 m (i 1.d
uPont de Nemours & Co, , I
nc, , Wi 1mington, Del.
re). Freeze-drying is done using Unitrap-1f or Model 10-147 HR-B^ (Virtis C
o, Gardiner, Hew Work).

Filter sterilizer (0,2) is Nalgene Fil
ter Stcrilizer (Nalge Co,,
Rochester, New York), and the cream separator was an Electrocrcam model.
116036 (1984) was used.

Postpartum colostrum is produced by Mycobacterium bovis (Hyco
bacterium bovis) antigen (tLbovi
Purified protein derivatives obtained from PPD-B) were obtained from dairy cows immunized or unresponsive to PPD-B).

380 g of each crude colostrum sample was heated to 4°C.
The cells were sedimented and solidified by centrifugation for 30 minutes.

The fat on the surface of the supernatant was scraped off, and the remaining supernatant was decanted. The decanted supernatant was heated at high speed (25,000°C, 4°C,
Centrifuge for 30 minutes to remove any residual fat or solids. The decanted supernatant obtained after this convex-speed centrifugation is called colostrum neem. Colostrum whey (a)
W analysis, (b) phenol and ether extraction, (C)]
- Tanol precipitation, (d) single-layer chromatography and C developed by the inventors listed below.
E, human 1-1] used to purify -1-F from IF and human IRTF ((e) Vol.
Ne-1~ri [17 Tographie [14 Ilson, G.
B, Paddock, G, V, and rudoIlb [!
I'tl, ++, ++, 1982. rl+ymus
4:335; G, B, Willon et al., 1
983: Immunobiology of 1ran
sfer Factor(Ni1rltllall'ic
k, C, 11,, Lawrence, 11. s and B
ur (ler, 11.R8) Academic Pre
ss, pp, 331-346; 1bid, p, 213
Subsequent fractionation was carried out in J.

Preparation of Colostrum Cell-Associated 1-Transfer Factor Specific for B, H. bovis Colostrum leukocytes obtained by the method of Example 1A were disrupted by freeze-lyse lysis. The Shiramen method disrupted material was dialyzed against pyrozene-free sterile water, and the dialysate (containing Dll) was lyophilized. The lyophilizate was redissolved in water and extracted with phenol and ether. Extracted water stratification containing cell-associated TF was subjected to stepwise fractional ethanol precipitation using 0, 5.1.0.2.0 and 4.0 volumes of ethanol. (2) The containing fraction was further purified by cellulose thin layer chromatography.

C. TF activity test method for colostrum whey or colostrum whey fractionation products using eye+vivo and in v+tro 1 The image was tested in vitro.■[
has traditionally been defined as a substance extracted from immune cells that can transfer delayed-type hypersensitivity-specific antigens in vivo (Wilson, G., B., &
bcrg, 11.11.1983, Immunolo
gy Today 4:157). Delayed type hypersensitivity 1
H. bovi to prove transfer in vivo
Various ωs of 1'1 from colostrum of cows immunized against s were administered intraperitoneally to Ba1b/c ma.

A bovine analogue that had not been immunized against H. bovis or lilin was administered to Bal b/C mice in groups I-1j. A standard measure of hypersensitivity in mice is foot pad swelling after 24 hours.
Lest, Gray, 0. [, and Jan++1nos
, P, 8, 19! +! i 8+ncr, 1lev, l
ul+ercPu1monary Dis, 72:17
1; Van Dijk, If, Versteeg,
11. and lIe++n1nk, 11. J., ,197
6, J, In+n+uno1. Hetl+od12:
261), the reactivity towards H, bovis was measured. ■ F talkability in VitrO was measured using a newly developed method, namely leukocyte transfer [+tlll damage] using peripheral blood white surface method obtained from non-responsive humans to H. bovis as target cells. Examination (IeukOcyte f
f1iQrati0111nhibition[LHI
] test] 1lson, G. B., and Fudenb.
erg, 11.11. .

1981, Lymphokines 4:107).

(i) T'Fe obtained from or in colostrum whey. Ba using fractions
IC results obtained with l b/c mice are shown. Only colostrum whey obtained from cows immunized against H,bOViS, or a 1 q fraction thereof, had a positive redirection activity of delayed-type hypersensitivity to 71x. Furthermore, a series of fractionations from colostrum whey ()-nol-ether extraction, ethanol precipitation and cellulose ILC
IF was irritated by the ability of the crude Ho 1- (equal or better) to the latent 11. Regarding the substance that was present, C is both 1nvivo and in vHro ■[
No activity was detected (see section F), and only the dialysate (substance that passed through the bag) showed 1F activity! Here is t[I
Deserves an F.

Table 2 Bal b/c shown by Paradobst
Injection transfer of delayed-type hypersensitivity to H, bovis in mice Footpat response 8 1° (a) H, bovis immunized cattle 30.00
Colostrum whey from b (b) Colostrum whey from H, bovis non-immune cow 8.00 (C) Zareen control 3.002° (a) 1
(a) J: Retrieved rc 32.00 bTF-containing dialysate (b) Similar substances contained in dialysate obtained from 1 (b) 7.00 (C) Saleen Control 3.003° (a) 2
(a) Refined/-/L, 50.00 b-TFF fraction after ether extraction (b) 2(b) phenol from 5.00-TFF similar fraction after 1-thyl extraction ( C) Saleen] Point U-Rule 3.004°(a) 3(
a) Yoliethanol precipitation m 42.00b and cell []-
After thin layer chromatography, TF-containing fraction b) 3(b) was precipitated with nitanol 4. Similar fraction after OO and lerulose static layer O madography.
24 hours after injection of PPD-8, the pad thickness increased by 0.01 ma+.

b, significant increase (P<0.01).

The leukocyte migration inhibition (old) test has been shown to be a reproducible and precise test used for the detection of
nbers, 1981).

Table 3 shows the PPD-8 of the test fractions of colostrum and colostrum whey.
1. of TF activity against Shows typical results from the old test. This result, shown in Table 3, is consistent with the original concentration of the material, such as colostrum whey, or the previous stage from which it was obtained, if purified by e.g. dialysis.
This is the result obtained when the image was reconstructed at the same angle (0 degrees). Only colostrum obtained from cows immunized against H. bovis had activity to induce PPD-8 responsiveness in human leukocytes that were non-responsive to PPD-8. was.

No TF activity was detected in fat removed from crude colostrum by centrifugation, and colostrum whey obtained from H. bovis nonimmune cows showed cellular immune responsiveness to PPD-8 in vitro. (containing 1F specific for PPD-8) and I
C).

After dialysis of colostrum milk against water, the substances remaining in the dialysis bag and the substances found in the dialysate (MW<20.0
PPD
It was clearly shown that all substances capable of generating cellular immune reactivity against -8 were present in the dialysate (Table 3). These results indicate that TF is MW<20.000 (IIIilsOll and Rudenberg, 1
981) is consistent with the inventor's claim that it exists in colostrum 1-.

Table 3 PPD-8 in colostrum whey J3 and dialyzed colostrum whey
Recording of 1-transfer factor activity against 1-transfer factor activity Test Substance Test M Small 1- Colostrum whey obtained from PPD-8 non-responsive cow 30 ~ 10.0 obtained from PPD-8 immune cow Kara' 40 - 5.0 dialysis bag residual material after dialysis of colostrum Whey PPD-8 immune Bovine colostrum 16 + 21.0 dialysate a8% DB from small nee = (1-MIB/old, ) x 100
%IIB(11)+15 is significant (p<, oi) and is due to -C present in the test substance.
We understand that anti-1 Hataketatsumi responsiveness has occurred. Transfer coefficient (n+ig+°ati011111 (IOX) derived by comparing cells incubated with a test substance and antigen in a solvent and those incubated with only the antigen.

Incubate 1 by containing the test substance in HMA-solvent.
Transfer index derived by comparing cells treated with ~ and those treated with solvent only.

Table 4 shows the results of the previous tests on the cell-derived fractions obtained in Example I B (-11J). 1F activity was observed in the material. TLC was found to improve the purity of I'.

Table 4: Recording of fractions obtained from colostrum white surface method disrupted materials from 1 to 10% of the fraction obtained by the white surface method Test Substance Test amount 1 Active phenol and ether 20 + 21 Leukocyte dialysate after extraction and ethanol precipitation The material a0%D, further purified by ILC 40 +23 , is as defined in Table 3.

H]・Cells alone, i.e. without test substance H, l
+ovis (100μ9/mf!) k: No specific capacitance to 1S0 E, other results of A P l) Latent TF specific to D-8,
For colostrum from cows immunized against PPD-B, and for mycobacterium off-A of the dialyzed colostrum.
H, for Luitum (PPD-l
), Mycobacterium marianome (u, +na
riallun+B111)ou) and Mycobacterium in1-rahiruler (H,1ntracel
lulare) (PPD-1) was tested. Bovine CI PPD-1, l
Or, it turns out that H doesn't have any immunity. As shown in Table 5/j results 11. Colostrum obtained from cows immunized against l+ovis is P 1
) Immunity 1'l only for IJ-8 14I-1),
+11) No immunity against 11-1.1 or 11. This is used to immunize cattle with 4 hours of different 1-transfer 1--
Only one horn is produced, and this is achieved by 1j
This is one of the sources of selectivity.

Table 5 Specificity test antigen of I in the dialysis fraction of colostrum whey
[1 activity (%D8) PPD-B O,94/ 0.79 (+16)PP
D-MO, 94/ 0.92 (+2) PPD-F
O,94/ 0.95 (-1)PPD-10,94/
0.99 (-5>a, activity of 16 μp of the dialyzed fraction of colostrum H from cows immunized against PPD-3.

%DBlff+ should be 15 or more.

(i) Coccidioidcs imn+1tis
TFe 21 Tukidy Aides immi, which is specific for
Tis (Coccidioides 1mm1tis)
Formalin-fixed microspheres obtained from 111k pre- or postpartum colostrum samples from dairy cows previously immunized with certain microspheres. c, i+++m1tis is a fungal organism that causes disease in humans. Dairy cows obtain T t' O with the desired specificity in postpartum colostrum/demonstrate the need for secondary immunization 1 .

3,000~12,000J of crude colostrum sample,
Centrifuge for 15 minutes at 4°C to sediment and solidify the cells.

One scoop of fat was removed from the supernatant, and the remaining supernatant liquid was diluted (10 ml).An equal volume of chilled arena (4°C) was added to the supernatant liquid while mixing. Obtained: compound i2.ooo
g, centrifuge at 4°C for 10 min, force 1 in.
The pudding, the protein powder and the surplus were sedimented and solidified.

The supernatant was concentrated using a rotary evaporator to remove the arenes and reduce the volume. Hat the observed substance
(lene O, 2μ5terile filter
Sterilized with Ullft. Lyophilize the aqueous concentrate to obtain TFe
Contains a dry residue of n.

(11) Fe C, 1mm1tis specific for herpes simplex virus (IIsV) (7) Generation VJ 4. Zll5V
Example 2-8 was repeated using dairy cows immunized with E4i-1.

A dry residue was again obtained.

(iii) He specific for Marek's disease (HD) virus. Commercially available leek 1-revacudine containing live Marek's disease virus was used in place of C, 1 mm, 1 eye S for immunization!
Example 2-A(i) was repeated using dairy cows.

A dry residue was again obtained.

(1v) 7A1 was produced using dairy cows immunized using a commercially available chicken vaccine containing live Newcastle disease virus, instead of C. Example 2-8(i) was repeated. A dry residue was again obtained.

(v) 12N against infectious bronchitis (IB) virus
A commercially available two-way strain containing live infectious bronchitis virus
Example 2-Δ(i) was repeated using dairy cows immunized using ˜Revacudin in place of C, 1 mm 1tis. IJ the dried residue again.

(vi) Bird laryngotracheitis ([1) C-specific He 1~rilaryngoqi for viruses? Immunize the chicken with a commercially available chicken vaccine containing 9 bacteria of the 1-inflammatory virus in place of C.1mm1. .: Example 2-A(i) was repeated using dairy cows. Add 1/4 cup of dry residue.

(vii) Bovine tracheitis (dairy cows immunized using commercially available bovine vaccine containing live HeBIT virus specific for the old (1) virus in place of c, i+nn+1tis) Example 2-A(i) was repeated using 25. A dry residue was again obtained.

(viii) Preparation of defrost with cream fraction lllllgN Example 2-A(i)-(vii) was repeated using a cream separator instead of centrifugation for removal of fat and cells. When cream fraction 1IIIN was used, similar results were obtained using centrifugation and IC.

(1x) Preparation of materials from milk Example 2-A(i)- Using milk instead of colostrum
(viii) was repeated. Similar results were obtained.

(X) Preparation using high-speed centrifugation Example 2-^(+)-(Vii+) was repeated, and the decanted supernatant was subjected to high-speed centrifugation (18,00 ol
)) L/, excess material (e.g. casein) was removed before the precipitation step.

(Xi 19 volume of sedimentation 1 volume to the sedimentation stage of the sedimentation method)
7 L tons of volume 111 was added to precipitate Il'e, and U1 Example 2^(i)-(viii) was repeated (i.e. A L-1
- The capacity ratio of water stratification to water stratification is 9 = 1). mix 12
,000g, 4°C for 10 minutes. The sedimentation of 9 volumes of Il is a woody alternative to the rotary vaporization and freeze-drying described in Example 1-^(i).

8.1”F activity test method (i) in viLr.

Example 2-^(i)-(For IC residues collected in Xil, spherules, 115V-1, NO virus, N
υ virus, IB virus, [1 virus or l
Against the old virus: 11-responsive Hi-1~! -4 from J stone! Activity was determined using the 181 test of Example 1-C, using peripheral blood leukocytes as standard cells.

(ii) in viv.

Varying amounts of each product (10-4,000 μρ) were administered orally or to specific pathogen-free (SPAr^) 1- to 30-day-old White Leghorn chickens or non-vaccinated commercially available White Leghorn cocks. It was administered by intramuscular injection and the in vivo activity was tested. Two to 30 days after administration, it was measured and evaluated whether specific cells that were induced to be immune to the respective antigens were induced in the chickens. Evaluation was made using agarose [old test (V, Nagaraja, J, A, Ncwm
an and B, S, pomeny, ^+n, J,
Vet, nes, .

1982.43+916-918. (more applicable).

White blood cells were collected by cardiac puncture and incubated with Vaccine of the Gods before being punched into agarose plates and placed into wells.
1~, 56°C, 15 minutes). 110. 15 previously vaccinated with NO, IB or 11 vaccine
~30 week old White Leghorn chicken, 5 PAFA
Leukocytes were also collected from small Leghorn roosters that had been vaccinated against specific pathogens and had not been administered the test substance.

C0 Results obtained by the above procedure - (+) day 1v rO [Old test Table 6 shows results obtained in Example 2-A(i)-(vii)] A summary of test results for viscosity against various pathogens in colostrum residue. The results shown are that after 1 volume (fi) 1 and 1~n sedimentation, the IF remaining in the 1-word (which has special properties against BP'l or small spheres) is 9 volume (fi) and 1~n sedimentation. This indicates that J will be recovered.

(ii) In vivo test: Immune S% i! 7 i
Table 8 shows the transfer of 11 cells to one cell lineage and LT2 cells.
This table summarizes the range of old (migration inhibition) values obtained in old tests for chickens non-immune to ND, HD, or IB. Prior to administration of samples containing TF, neither SP8[^chickens nor non-vaccinated commercial white leghorn chickens (commercial non-immune chickens) responded to any of the four viruses or BRT. Ta.

After administration of the TF samples, both 5PAFA and commercial non-immune chickens showed similar responses to each of the four viruses, and this result, shown below, is independent of the type of chicken tested. .

The effect of the TF sample depends on the dose (10μ per bird).
! (tested in the range 2-4,000 μA), the effect is independent of the route of administration (oral/intramuscular).

Table 6 Concerning the colostrum fraction obtained by acetone precipitation freezing of 20
Small sphere +21 redissolve dry matter 20 11sV-1
4-24 40 Ll -1-23 30NO+33 3o HD + 28 40 1B -+-30 a, obtained in Example 2-^(+)-(iX) / IJ material was redissolved in pyrozene-free water Human target cells were used (2x) after filtration and IC [in the previous study].

b, BRT, small sphere, 115V-1, LT, NO, 80
and IB as defined above.

C1%D8 is the same as defined in Table 3.

Table 7 IFV recovery test of acetone precipitated solution with 1 volume of acetone sedimentation Substance C antigen bLH 1 volume 0 volume
-N alLt 20 Reconstitution of upper liquid 11 with BRr 422 2o Small spheres -1-21 1 volume ff17 Cell precipitate EV 2o B+++ 120
9 volumes of 1r1j'L I-n20 microspheres +29 precipitate redissolved a, b, c, same as definitions in Table 6 and in Light III Mi.

Table 8 Cells that have acquired immune responsiveness: Responsiveness shown by two vaccine immunized and two non-immunized tests against Ll, HD, 80 or IB viruses.

Old Old ft1a Antigen No response Non-immune Immune cut Afu (N) (N)' Lr O,850,85-1,03(23) 0.59
-0.77(8)NOO,900,91-1,17(1
8) 0.45-0.88 (8) HD O,900,9
0-1,07(17) 0.56-0.79(7)IB
O,900,98-1,18(17) 0.59-0
．． 85(9)a, old-migration index
1ndex) b, N (non-immune) - number of groups of test chickens c
, N (Immune) - Population of Chickens According to the results shown in Table 9, the fractions obtained in the reconstitution of the supernatant of one volume aliquot of colostrum whey, 11.811.811 or the IB virus has been shown to be capable of inducing immunity in individuals who were non-immune to the virus. In each case, fractions obtained from cows immunized with each chicken vaccine and cows not immunized with each chicken vaccine and cows only immunized against the old (1 virus) were combined. From '4 [
We compared the effects of similar products.

Chickens administered fractions prepared from cows immunized with four types of chicken vaccines were LT, N011.
B, B11 became responsive to HD and B11F, whereas fractions prepared from cows not immunized with the four chicken vaccines induced immunity in chickens only to B11F. This is interestingly pointed out. As shown in Table 10, 1 volume f; 1
7t? A 9-volume acetone-precipitated reconstitution of IC-active supernatant obtained from a ton-precipitated sample rapidly induces immunity in chickens.

Table 9 Effect of fractions obtained by acetone precipitation of colostrum on immunity in chickens
μp) Chicken vaccine! i00 LT O,71 immunized Old 1 0.69 1 volume from bovine colostrum IB O,G7 AL? Nil 0.73 was obtained by sedimentation of fresh liquid B
11I O,1' (i Reconstituted Two Wa) - Revaccine 500 LI O,9 (by i (immune only against B. filus 811 0.98) IB 1.08 from bovine colostrum 1 konffi 8
11 1゜00at? BRI' by l-ion sedimentation
+1. ii5 Reconstitution a of the supernatant obtained. The results are average values from experiments conducted on independent nY of 4 or more groups.

Table 10 Immunity-inducing effect on chickens of 9 volumes of acetone-precipitated re-dissolved 47 volumes obtained from colostrum.Immunity-inducing effect on chickens.Two doses of antigen response sample a (μ!2) 1.587- 823 500 N mouth, IB O, 74;
0.752.587-827 500 NO;IBO
,69;0.693.189-67 500 ND;H
DO, 79; 0.674.224-911 500
ND; NOO, 64; 0.50a, 9-volume acetone-precipitated relysate of colostrum sample from one comb immunized with all four chicken vaccines. The number is the trial F1 number.

b, MI values were determined using three or more different groups of chickens and 1 = mean value of the experiment.

Song 14 Kudan A, He A (+) C, 1iti + 1tiS Colostrum was obtained from cows immunized with corpuscles, fat and 111 follicles (1 Example 2-A(i) and 1ij) properly removed. Low fat 1" acid, 12,000H, I4
．． Using a dialysis membrane of KA-1 (4 times the volume of cold I)
Dialyzed twice against J1 sterile steam water. (1) The dialysate (substance that passed through the Rinawara membrane) was collected and concentrated by lyophilization.

(tm~su@cephalic bronchitis (January virus example 2-A)
Example 3-8 was repeated in the same manner as in vi) using the colostrum collected from cows immunized with the virus.

(iii) Newcastle disease (NO) virus Example 2
-1 from a cow immunized with ND virus as in A(iv)! Examples 3-8 were also repeated using colostrum.

(iv) Infectious bronchitis (IB) virus Example 2-A
Examples 3-8 were repeated using colostrum obtained from cows immunized with IB virus as in (V).

(v) Marek's disease (HD virus) Example 3-8 was repeated using colostrum from a cow immunized with NO virus as in Example 2-(iii).

13.11 Activity Test Method The TF activity of the freeze-dried residue obtained in Example 3-8 was determined by the method of Example 2.

C1 The result of 1!1 by the above /J method (i) in
The substance obtained in Example 3-A(i) induced responsiveness to microspheres in HiI-III cells, which were non-responsive in the previous test (in the solvent). When cells are incubated with microspheres in
There was 1C).

(ii) in viv.

J shown in Table 11, sea urchin Example 3-^(iii)
1) Radical 71 has the ability to induce antigen-specific cells with immunity against Caucasian disease in chickens. Table 11 shows Example 3-^(i
The material obtained in ii) was repurified using the weighing method described in the previous example. Also includes data on ζ.

Table '11 N in chickens by injection of fractions obtained from colostrum by dialysis, phenol-ether extraction and acetone precipitation.
Induction of immunity against O virus.Dose administered to chickens.Response to ND virus sample (μ!;/)
1 - Reconstitution of aqueous stratification tubed after extraction 3.1 1 volume acetate 250 0.741 - Redissolution of supernatant by sedimentation 4.3 J 250 0. (129 capacity 7L?
Re-lysate of sediment A, results based on the average value of 1:1 experiments on more than 3 independent groups of non-immune chickens administered with the above sample.

Example 4 Preparation of A, ■[e] Colostrum was prepared by the method of Example 2-8m (11), and fat cells were removed. Low-fat product in equal volume of cold 141 Isop E.
Mix it with panol. 12,000'/, 4
Centrifuge at ℃ for 10 minutes to sediment and solidify impurities.

Furthermore, add 1 panol to the cooled isop 1) iii liquid,
Finally, 1 volume of aqueous liquid is mixed with 1 volume of isop[1 panol 2
I made it acceptable. Then add 12.000g of pentacontains.
The mixture was centrifuged at 4°C for 10 minutes, and the precipitate was collected. - The supernatant was further treated with isozo['panol] (up to a ratio of 5 volumes of isozo['panol per 1 volume M of aqueous liquid). Centrifuge the remaining 1 ml in the sediment again.
was recovered.

B, TFe activity test method Example 4-8 1! The 1F activity of the obtained substance was measured according to the old test method of Example 1.

C1 The results obtained using the above method are shown in Table 12, and the old test yielded 1! These results document induction of immunity by rFe, although not in non-responsive human cells. From the results shown in Table 12, it is clear that the yield of 1F can be maximized (t) by adjusting the volume and weight of the added isobutyl alcohol.

12th person In the colostrum fraction precipitated with isopropanol, 2 volumes of isopropylene 40-1-: redissolved precipitate obtained with 17 panol. J, S1!] Re-lysate of precipitate a, white sphere transfer port 1 J, C, response to microspheres in human L1 standard cells as shown in 3.1 response to addition of test substance. If not, all 1111 cells are non-responsive to microspheres. %D is the same as in the 1f13 table.

Example 5 A, [f Colostrum 1- is prepared by the method of Example 1, prepared from colostrum of cows immunized with bovine parainfluenza virus by low speed followed by high speed centrifugation. did.

B. TF activity test method The activity of the obtained ① was measured in VitrO'c according to the old test described in Example 1.

C9 The results obtained by applying the above method are shown in Table 13. Measurements of 1F specific for human mumps virus document induction of immunity by TFe, although not in non-responsive human cells. Furthermore, the substances obtained and tested in this example may be fractionated or repurified and sterilized by the method described above. In this way 1!7
A sterilized J, highly active product G, Lhij ~ administered to mumps patients to alleviate or treat the disease! -J'1J is possible. Furthermore, the 1F-containing product confers immunity against the disease in humans infected with the mumps virus. It is also possible to administer it to the rice. J3C is also used for intracellular immune responses against panmyxovirus (・aruhi), mumps virus, and bovine parainorcone IJ'r virus.
The results indicate that one-phase U reactivity exists.

Table 13 Induction of immunity to mumps virus or bovine parainfluenza-3 virus by colostrum H in human cells as shown by leukocyte migration inhibition assay. Milk whey 15 Mumps +20 Sample 716-2 Virus 0 Colostrum whey 1- Parainfluenza +35 Trial 754-1 Enzyme milk, colostrum small knee undergoes first low-speed centrifugation followed by high-speed centrifugation. Prepared by removing cells, debris, fat and casein.

b. By inhibition of leukocyte migration using target cells that are unresponsive to each antigen alone (without the test substance).
(Response to each antigen shown.

EXAMPLE 6 A. [1 Colostrum honey is immunized with bovine parainnormium 3 virus/j bovine colostrum l) item 11 (prepared by high speed centrifugal valve-1 followed by high speed centrifugal valve-1) Prepared according to the method of Example 1.

B,l'l''nZ (!I test PJ) The activity of 1 obtained in I nonno was determined by the 111v ro U alQ test using 1C and 1C in Example 1. Shilko.

C1 above h) J, S111, and the following are shown in Table 13. Although the specific results of 1 [1] specific for the bovine Innorrhea 1f-3 virus did not occur in J1 cells, they recorded the induction of immunity in 11 (! are doing.

]; Continuation City jlE 'ff1-! -! 1111 和604r-February 22I] 1. “Bian′ [Chief of the Agency G□j Manabu 1, 'J+I′1 display 11+) 和5qi [Special revision request No. 2/1790
37 2, Title of the invention lj method for obtaining transfer factor from colostrum, thus C'R: ~Use of transfer factor and child 31+Ii positive person's small i'1 relationship Special 7 [Application Person Name Amt 1j N In= 1-Boreited 4, Agent East ≦ Mitoshin 1i1 Mecha 11 Aozuki [11 Rai 14
+':j +DIIl Hill 55, Loiri of supplementary instruction White Light-＼ 7゜Object of amendment Specification 2':,:'8, Contents of amendment lsu1ryu11;middle,4'InClaims Please refer to the attached sheet. , Formula 7 ('rゝ) + 1 (Claim 1 Claim (1) The secretion from the mammary gland of a mammalian animal that secretes appropriate milk is used against the antigen.・-) 7 ctor (1-Fe) t'+'=It is characterized in that it is collected under suitable conditions such that substances that interfere with the effectiveness of the 1~nsnoarfactor are removed as much as possible. 3. The method according to claim 11, wherein the material is colostrum.

(3) Komaaki'I which is a substance or milk Claim No. i J
The method described in Ql.

(4) Appropriate milk-secreting mammals or immunized against antigens.
7j payment as stated in 12.

(!l) Appropriate Article A (1 includes the processing of said calculations for recovering transfun-no-fu-futa from the collected material! Scope of 111 Requests as described in No. 11!) Jj method.

(6) The method according to claim 5, wherein the treatment is ultrafiltration.

(7) The processing is transparent (1￥Jn'l Claim 5
The method described in section.

(8) A method according to claim 2, wherein the colostrum is processed to substantially remove cells, cell remnants, fat and fat.

(9) The removed cells are excreted by the cells
-Avoid contact with the antigen under appropriate conditions to avoid releasing the knockter! 1. Scope of Requirements The method according to item 8.

(10) The method according to claim 9, further comprising removing cells, concentrating or purifying the transnor-7-factor, and then sterilizing the concentrated or purified transnor-7-factor.

(11) The method according to claim 8, wherein the treatment includes low-speed centrifugation for a fixed period of time, followed by Hatakesen delivery for a further fixed period of time.

(12) Treatment or low-speed centrifugation for a certain period of time, followed by addition of an appropriate amount of an agent v'j that substantially precipitates C-munoglobulin. The method described in.

(13) The treatment includes low-speed centrifugation for a certain period of time, followed by ultra-reduction (h payment as set forth in claim 8, 2(14))
Processing involves low-speed centrifugation at a constant 1υ1 followed by 4 bars.
I': Scope of crystallization The method according to item 8.

(15) Furthermore, flash shrink or purify 1~Lance Horn - Horn Lid), and then sterilize 7 Lid (1~Lance Horn--) made by Fuchi shrinking fl'J. Including Koma'
1. Scope of request: Those listed in item 8 v1゜(16) Cells, cell remnant layer, power L-in, and fat v'1
I'm going to treat the removal of breasts r1! I n'11.
The method according to claim 3.

(11) Transfer the removed cells to cells 1 and 7'-
17. The method according to item 16, wherein the lid is brought into contact with the free liberated antigen at a suitable distance.

(18) Further remove the cells and
18. The method according to claim 17, which comprises concentrating or preparing the lid, and then sterilizing the concentrated or purified transtsuno-factor.

(19) The method according to claim 1, wherein the antimicrobial agent is a microorganism or derived from a microorganism.

(20) The method according to claim 19, wherein the method is derived from antibacterial bacteria or bacteria.

(?1) The method according to claim 20, wherein the bacteria is Mycobacterium bovis (-).

(22) The method according to claim 9, wherein the antigen is a fungus or derived from a fungus.

(23) The method according to claim 22, wherein the fungus is Xidioides imidis C.

(24) The method according to claim 19, wherein the method is derived from a 100 million yen or a 100 million yen or a protozoan.

(25) Anti-1 quintillion virus or virus 1-1. mountain from the virus)
14 Claims No. 1. [written in the mouth)) law.

(26) Virus or Nakatsumugi rash virus-c a'o)'
12J ii'l Claim 20 Chouguchi J1 Clause 1 Fire no)) Person.

(27) μ゛Virus C' included in a3 of Virus Crab 1~:! ]Recited in Claim No. 251j'j)
Law.

(28) Virus in cows;! 4. Tracheitis 1 Noilus C
Yes: 1. Scope of lr1!1 crystallization The method d) described in item 21).

(29) Virus! 1 parlay fn norland 1
Claim No. 2514 is written in claim 2514. Second! J
/'J 7)s described in IJ"j.

(31) Virus or 7.Ll
, I. The method according to claim 25, 1. (32) The method according to claim 25, in which the virus is infectious bronchitis, f.

(33) The method according to claim 25, wherein the virus is laryngotracheitis virus.

(34) Claim 1 in which anti-1iJ< is cancer-related
The method described in section.

(3!i) Collect secretions from the mammary glands of suitable milk-secreting Ili mammals, collect whole cells from the collected material, and then use the whole cells thus collected against In order to inhibit the specific intracellular 1~Lansf1-factor, the anti-15 anti-1~1-factor may be treated under appropriate conditions such that substances interfering with the efficacy of the 1-~Lansf~1-factor are removed. 1116h method, 1(36) treatment or 1 for 1h different intracellular 1~ranfufu-horn-lid against Kyoto
~Cells are disrupted to avoid release of Toshinsuno I-factor, and then Toshinsuno I-non-factor is extracted from the destroyed cells.
36. A method as claimed in claim 35, comprising collecting the lid.

(37) The method according to claim 35, wherein the cell destruction includes freezing and thawing.

(38) The method according to No. 35, n, for recovering or ultra-reducing (including excess) 1 to 1 to 1 to 10 cm from destroyed female cells.

(39) Collection of 1-nonsunono-horn-lids from destroyed l'jl cells, including l'jl containing Toru 4J1.

(40) Further comprising concentrating or purifying the 1~Lansnov horn lid, and then sterilizing the 1~Lansnow factor produced from the J layer line to 11ilI!'1! l
i+'l The method according to claim 35In.

(41) The secretion of the mammary glands J and ri of a mammal that secretes appropriate milk is expressed as -c ′I! 1 different 1 no I
+H+-, something that overrides the effectiveness of the transhorn-no-j lid to increase the non-sunon-factor by 4j7
jjj or removed J, una) collected in the proper row 1'1 small - (ij7 collected JJI It + ?'nonsno fun - non 7 ctor.

(42) Antigen is mi] Pakte 1 family sim small bis, "Kushiji A ides immitis El $tun 10 rash virus, Hi 1
~'s d3 mumps virus, bovine tatami tracheitis virus.

Cattle parainnornivirus, 2:1-ki (
7. Species 1 to 7, which are Tsururu's disease virus, Marek's disease virus, infectious bronchitis virus, or laryngotracheitis virus, according to item 41.

(43) The discharge 1 to the lactiferous lactate according to claim 41, wherein the milk-producing animal that secretes milk is a cow.

(44) The substance r1 is colostrum C, and the cells removed by processing the colostrum are brought into contact with an antigen so that the cells υ [output 1 - transfer) 1 vector are released] Claim 41 Emissions 1 to Lancets 7- as described in any of Items 43 to 43
Nono lctor.

(45) The substance is milk, and the cells removed by processing the milk are excreted and free of contact with the antigen. Box No. 41
As stated in any of paragraphs 43 to 43, published on June 31st, Tonon Snowflake 7th Edition.

(46) Collect the secretions of the mammary glands of mammals that secrete milk, collect whole cells from the collected material, and then collect the whole cells using anti-1 ! against it-
C'4:+Inside the cells 1~14) The thing that crosses the effect of the I~Lance horn -horn lid by 1'i! ■ After removal, appropriate treatment ('l l'C treatment) is performed to remove intracellular tissue.

(47) Anti-1jJj or mini-1 bacfulium small bis,
” Kushiji A Ides Iminus, Papella virus, H1
~'s ilj 5 Kuka C virus! 1-4: Electric tube inflammation virus.

Cow's home°innor1n1au2frus,nee]
-='+: T. tsusuru disease virus, Nrek's disease 1, infection 14 bronchitis virus or laryngotracheitis virus -C-1,'
The intracellular 1-synthono-factor described in .

(48) The intracellular transfection knockter according to claim 46JJj, which is a milk-producing animal or a cow.

(49> C-specific excretion 1 to Lansfu I for anti-1jJj
-) An edible composition comprising an I-lid and a suitable edible carinore, wherein the lance-force factor is adapted to absorb the secretion of the mammary glands of a mammal that secretes suitable milk into an anti-1 quintillion U 'l'jjDifferent emissions 1~transfer factor lrl<l<or under appropriate conditions 1'1 such that substances that interfere with the effectiveness of the l~ransfactor I-factor are removed.
C- Edible composition assembled into IE7.

(50) Antigen [Specific intracellular 1-ransufu
An edible composition containing 7-factor and a suitable edible key (7-factor) was prepared by collecting secretions from the mammary glands of mammals that secrete milk. Collect all cells from the material, then 'C-koshi-(anti-1j;
Items that exceed the effectiveness of the lance tour horn/lid by 1 or T1 will be removed.
Edible composition obtained by C treatment.

(Nil) to immunize C against anti-ILξ in humans or lower animals containing a medical carrier and appropriate pharmaceutical or P. 5. A pharmaceutical or veterinary composition for feeding said lactator or lactiferous animal. +f J,
d・object to anti-1jJj 'l='J hole I
Eye 1 ~ Nonsu no no - Horn Lid - (Cj l
Substances that interfere with the effectiveness of the 1~nonsunono-horn-lid will be removed. Also (.1, animal 1shi, scientific composition.

(52) A veterinary composition for use in immunizing against bovine M. bovis, monoplegia virus, bovine tracheitis virus or bovine parainfluenza virus! 51. A pharmaceutical or veterinary composition according to claim 51.

(7) The pharmaceutical or Veterinary composition.

(54) Features used to immunize against H. immitis, H. leprae virus, and mumps virus of H.1. Claim 5
Pharmaceutical or veterinary composition according to item 1.

(55); Pj to immunize humans or lower animals with a dose of effective immunization intracellular 1 to 1 to 1 horns and lids and appropriate pharmaceutical or veterinary chemicals. 1. A pharmaceutical or veterinary composition for administering I.
Collect secretions from the mammary glands of mammals whose horns and lids secrete suitable milk, recover whole cells from the collected material, and then collect all the cells thus recovered.
171 different intracellular transhorns with respect to JitlJa
- A pharmaceutical or veterinary composition obtained by treating the horn lid with a suitable method to remove substances that interfere with the efficacy of the horn lid. .

(56) The veterinary composition is used to immunize against bovine Bacterium bovis, 10 simplex virus, bovine shishitracheitis virus or bovine parainfluenza virus. It'll be done! J i:'l Pharmaceutical or veterinary composition according to item 55.

(57) The veterinary composition is used to immunize chickens against Key-Tsuru disease virus, Marek's disease virus, infectious bronchitis virus or head tracheitis virus. 'F A pharmaceutical or veterinary composition according to claim 55.

(!18) "Kushiji Aides" whose W-chemical composition is Hi1~
Imitis, simple i! Eczema virus or Hi 1 ~ a3 infection I! '1 A pharmaceutical or veterinary composition according to Scope No. 55 In, used to immunize against viruses.

Claims (1)

[Scope of Claims] (1) A substance that interferes with the efficacy of transfer factor (TFe) specific to antigens in secretions from the mammary glands of mammals that secrete appropriate milk. A method for obtaining an efflux transfer factor, characterized in that it is collected under suitable conditions such that it is removed. (2) The method according to claim 1, wherein the substance is colostrum. (3) The method according to claim 1, wherein the substance is milk. (4) The method according to claim 1, wherein the mammal secreting suitable milk is a cow having immunity to the antigen. 5) A method according to claim 1, wherein the appropriate conditions include processing the collected material to recover the transfer vector from the material. (6) The method according to claim 5, wherein the treatment is ultrafiltration. (7) The method according to claim 5, wherein the treatment is dialysis. (8) The method of claim 2, wherein the colostrum is processed to substantially remove cells, cell debris, casein, and fat. (9) The method according to claim 8, wherein the removed cells are brought into contact with the antigen under appropriate conditions f1 so that the cells film the excreted transfer factor. (10) The method according to claim 9, further comprising removing cells, concentrating or purifying the transfer factor, and then sterilizing the concentrated or purified I. lansturthorn7ctor. (11) Special features in which the treatment involves low-speed centrifugation for a fixed period of time, followed by high-speed centrifugation for a further fixed period;! [The method according to claim 8. 12. The method of claim 81n, wherein the treatment comprises low speed centrifugation for a period of time, followed by addition of a suitable amount of an agent that substantially precipitates the immunoglobulin. (13) The method of claim 8, wherein the treatment comprises low speed centrifugation for a period of time followed by ultrafiltration. (14) The method of claim 811'4, wherein the treatment comprises low speed centrifugation for a period of time followed by dialysis. (1!+) The method according to claim 8, further comprising concentrating or purifying the trans7F-71 factor, and then sterilizing the concentrated or purified transfer factor. (16) The method of claim 3, wherein the milk is treated to substantially remove cells, cell debris, casein and fat. (17) The method according to claim 16, wherein the removed cells are contacted with an antigen under appropriate conditions so that the cells release transfer factors. (18) The method according to claim 17, further comprising removing the cells, concentrating or purifying the i-transfer factor, and then sterilizing the concentrated or purified transfer factor. (19) The method according to claim 1, wherein the antigen is a microorganism or derived from a microorganism. (20) The method according to claim 19, wherein the antigen is a bacterium or derived from a bacterium. (21) The method according to claim 20, wherein the bacterium is Mitsobacterium bovis. (22) The method according to claim 19, wherein the antigen is a fungus or derived from a fungus. (23) The method according to claim 22, wherein the fungus is A. immitis. (24) The method according to claim 19, wherein the antigen is a protozoan or derived from a protozoan. (25) The method according to claim 1, wherein the antigen is a virus or derived from a virus. (26) The method according to claim 11, item 25, wherein the virus is the single virus. (27) ``The method according to claim 25, wherein the virus is Toto 1- mumps virus.'' (28) The method according to claim 25, wherein the virus is bovine roaring tracheitis virus. (29) The method according to claim 25, wherein the virus is bovine parainfluenza virus. (3+1) The method according to claim 25, wherein the virus is Newcastle disease virus. Method. (31) The method according to claim 25, wherein the virus is Marek's disease virus. (32) The method according to claim 25, wherein the virus is infectious bronchitis virus. (33) >The method according to claim 25, wherein the virus is laryngotracheitis virus. (34) The method according to claim 1, wherein the antigen is cancer-related. (35) Appropriate milk secretion The secretions from the mammary glands of mammals are collected, whole cells are collected from the collected material, and the whole cells thus collected are then transferred to the intracellular transfer vector to obtain antigen-specific intracellular transfer vectors. A method for obtaining an intracellular transfer factor specific to an antigen, which comprises treating under appropriate conditions such that substances that interfere with the efficacy of the factor are removed.
36. The method of claim 35, comprising disrupting the cells to cause the 1-transfer factor to be released from the disrupted cells. (37) The method according to claim 35, wherein the cell destruction includes freezing and thawing. (38) The method according to claim 35, wherein recovery of 1-transfer factor from disrupted cells comprises ultrafiltration. (39) The method according to claim 35, wherein the recovery of the 1-transfer factor from the disrupted cells comprises dialysis. (4(1) The method according to claim 35, which further comprises concentrating or purifying the transtour factor, and then sterilizing the purified 1-transfer factor. (41) Miko Intracellular 1-transfer factor specific for Baquarium bovis. (42) Bovine-derived intracellular transfer factor specific for Mycobacterium bovis. (43) Bovine specific for Coccidioides immitis. (44) Excretion transfer factor 1-factor specific to Coccidioides immitis. (45) Kareyama 1-transfer factor from cattle specific to Coccidioides immitis. (46) Mono@leprosy (47) Cattle-derived glue 1 that is specific to melanosis simplex virus.
Outtransfer factor. (48) Bovine-derived trans-tour factor specific to human mumps virus. (49) and I- an efflux transfer factor specific to mumps virus. (50) Kareyama 1-Shinsunono-7no7kta of bovine origin, which is specific to human mumps virus. (51) Transfection factor specific to bovine phosphorus tracheitis virus. (52) 14 different iJl against live tracheitis virus
Exit I Ransuf 1-Funofkter. (53) Bovine-derived transtour factor with Ej f< against tracheitis virus. (54) Cattle-derived IJI 1 to Lansnoano 1, which is specific to cattle fever virus. (55) A transtour factor specific to 11 parainfluenza viruses. (56) Specific excretion for live balaine true Lunza virus] - Lancetsuno 7-Nono? ctor. (57) For parainnovirus of η (unique cow-derived 1 to lansferno jν vector). 1~Lansfargin ν vector. (59) 2''-Transtour factor specific to Castle disease virus. (60) Excretion transtour factor specific to New Castle disease virus. (61) New 11 (62) New 11? Bovine-derived fJl-derived trans7?-factor specific to Tsusuru disease virus. (63) Bovine-derived fJl trans7?-factor specific to Tusuru disease virus. A unique transtour factor. (64) A unique transtour factor to Marek's disease virus.
It transfer factor. (65) Specific to Marek's disease virus! , 1 Originating from Yamarai - Lance Far Factor. (66) A bovine-derived efflux transfer factor specific to Marek's disease virus. (61) 1-Transfer Fluor Lid specific to infectious bronchitis virus. (68) For infectious bronchitis virus-C-specific excretion transf 1-horn I vector. (69) Bovine-derived 1-ransuit 1-factor specific for infectious bronchitis virus. (70) 15 different bovine-derived efflux transfer factors for infectious bronchitis virus. (71) Transfer factor specific to laryngotracheitis virus. (72) Spinning transfer factor specific to laryngotracheitis virus. (73) For laryngotracheitis virus, 'l' FJ different bovine-derived 1-transf7I-non-1 factor. (74) For laryngotracheitis virus, [unique bovine-derived 171-derived transno1 factor. (75) I obtained by the method described in claim 1
This emission transfer factor. (16) Intracellular 1-transfer factor produced by the method according to claim 35. (71) Emission transtour factor obtained by the method according to claim 9. (18) Emission transfer factor obtained by the method according to claim 11. (19) An edible composition comprising the transfer factor according to claim 15 and a suitable edible Yayaria. (80) An edible composition comprising the transfer factor according to claim 76 and a suitable edible carrier. (81) An edible composition comprising the transfer factor according to claim 77 and a suitable edible substance. (82) An edible composition comprising a transfer factor according to claim 78 and a suitable edible carrier. 1! A pharmaceutical or veterinary composition comprising the transfer factor according to item 1 and a suitable pharmaceutical or veterinary medicine: 1 Yarino'. <84) Claim 1 of Kawaishi that provides effective immunity
A pharmaceutical or veterinary composition comprising l-ransph 1-factor according to item 6 and a suitable pharmaceutical or veterinary medicine. (8!+) The transfer described in claim 17 of Kawa M that provides effective immunity? A pharmaceutical or veterinary composition comprising -7i7ctor and a suitable pharmaceutical or veterinary 1%-1=rea. (8G) A pharmaceutical or veterinary drug containing 1 to 7-factor and an appropriate pharmaceutical or veterinary drug as set forth in claim 78 of the chartered ship's claim that provides effective immunity. Composition. (81) Kawaishi's fourth claim provides effective immunity
1. A veterinary composition for immunizing cattle against the bacterium T. bovis, comprising a transfer factor as described in item (n) and a suitable veterinary killiaria. (88) Kawaishi's fourth claim provides effective immunity
A veterinary composition for immunizing cattle against the 01@J (itch rash virus) comprising a transfection 1-7/vector as described in item 6 and a suitable veterinary carrier. (89) Effective immunization Claim 5 of Kawam which provides
1. A veterinary composition for immunizing against TL bovine tracheitis virus, comprising a lance tourfactor as defined in paragraph 1 and a suitable veterinary carrier. (90) against fresh rose influenza virus in bovines comprising a transfer factor according to claim 55 and a suitable veterinary carrier for providing effective immunity - A veterinary composition for breeding. (91) Claim 5 of the dose that provides effective immunity
A veterinary composition for immunizing chickens against Newcastle disease, comprising a factor 1 to Ransnoj) according to item 9 and a suitable veterinary "Yaria". (92) V1 Revised Claim 63 for providing effective immunity and appropriate veterinary medicine 4. CLAIMS 1. A veterinary composition for immunizing chickens against fowl disease, comprising: (93) B. Claim No. 67 of the effective immunizing dose comprising the 1-Lansfarf 27 vector described in XQ and the appropriate veterinary %-11 vector against infectious bronchitis virus of chickens A veterinary composition for immunizing patients. (94) Claim 7 of the dose that provides effective immunity
A veterinary composition for immunizing chickens against laryngotracheitis virus, comprising a transfer factor according to item 1 and a suitable veterinary carrier. (95) Claim 4 of the dose that provides effective immunity
A pharmaceutical composition for immunizing humans against Coccidioides immitis, comprising a transfer factor according to item 3 and a suitable pharmaceutical carrier. (9G) Claim 4 of the dose that provides effective immunity
A pharmaceutical composition for immunizing against human 11 simplex virus, comprising 1-transfer factor as described in item 6 and a suitable pharmaceutical chirelia. (97) Claim 4 of the dose that provides effective immunity
A pharmaceutical composition for immunizing humans against the human mumps virus, comprising a transfer factor according to item 8 and a suitable pharmaceutical carrier. (98) 1-Lansf 7 as claimed in Claim 15 of Kawama's Claim which provides immunity to Effective 4? - A method of immunizing humans or lower animals by injecting horn 7 vectors into humans or animals. (99) Claim 1 of the dose that provides effective immunity
A method for immunizing humans or lower animals, which comprises administering the transtour factor according to item 6 to humans or lower animals. (100) A method for immunizing humans or lower animals, which comprises administering to humans or lower animals the transtour factor set forth in claim 71 which provides effective immunity. (101) 5 El Ill Di O) Effective Immunity
I: s i+'l i, claim (J) R2a I'll
19. A method for immunizing humans or lower animals, which comprises administering 1 to 1 to 1 to 1 to 7 stars according to item 18 to humans or lower animals. (102) Claim v of the dose that provides effective immunity
A method for immunizing cattle against Mycobacterium bovis, which comprises administering the transfer factor according to item 841 to cattle. (103) Claim 9 of the dose that provides effective immunity
1. A method for immunizing cattle against cold sores simplex virus, which comprises administering 1 to lansurtour factor according to item 6 to/to animals. (104) A method for immunizing cattle against bovine tracheitis virus by injecting the Transfer 771 vector according to claim 51 live at a dose that provides effective immunity. (105) A method for immunizing cattle against fresh rose influenza virus, which comprises administering to cattle the 1-71 influenza virus described in claim 55 for providing effective immunity. (10G) Claim No. 1 of the dose that provides effective immunity! ) 1 Heranshu 1-7 described in item 11? A method of immunizing chickens against the 2L virus by throwing chickens with chicken. (107) A method for immunizing chickens against the chicken blistering disease virus, which involves administering Lansfu 1-hornfucter to chickens. ) A method for immunizing chickens against infectious bronchitis virus by administering the 1-Lansfarf7?ctor according to claim 67 to chickens. (109) 4. How to immunize chickens against laryngotracheitis virus by administering to chickens the transfer factor set forth in claim 71 at a dose that provides effective immunity.
. (110) Administering an effective immune system to a human by administering the Virt factor 1 to Lansnor 7 according to Claim 43 to a human to immunize a human with Coccidis Aides immitis. 1. (111) A method for immunizing humans with the human varicella virus by administering to humans the transfer factor set forth in claim 46 of the Kawaishi patent, which provides effective immunity. (112) Claim 11 of a dose that provides effective immunity
11 Add the transfer factor described in Section 48 to
How to give immunity to a virus in a human with mumps. (IL/j: white)