CN103479607B

CN103479607B - Treatment or prevention rotavirus infection

Info

Publication number: CN103479607B
Application number: CN201310430147.XA
Authority: CN
Inventors: 米歇尔·阿夫里尔·麦康奈尔; 克莱尔·伊丽莎白·安·菲茨帕特里克; 阿拉斯代尔·凯尼斯·修·迈克基布恩; 凯瑞·特雷泽·布占; 格莱恩·斯图尔特·布占
Original assignee: Fonterra Cooperative Group Ltd
Current assignee: Fonterra Cooperative Group Ltd
Priority date: 2007-08-09
Filing date: 2008-08-08
Publication date: 2016-11-30
Anticipated expiration: 2028-08-08

Abstract

One or more conjugated linoleic acids (CLA), the butterfat of high CLA or one or more the Lac Bovis seu Bubali lipid compositions purposes in treatment or prevention rotavirus infection.

Description

Treatment or prevention rotavirus infection

Invention field

The present invention relates to one or more conjugated linoleic acids (CLA), the butterfat of high CLA or one or more Lac Bovis seu Bubali iipidomic Compound purposes in treatment or prevention rotavirus infection

Background of invention

Breast is a kind of for the neonate important source of nutrition of offer, nourishing biofluid.Additionally, breast is containing being used for The material (agent) of developing immune system, function and maintenance, this material is required for the growth of baby.

Rotavirus is the 3rd type (dsRNA) virus of Reoviridae, and causes about 1.38 hundred million babies every year Diarrhoea.The child of 95% can be shown effect by rotavirus diarrhea before five years old.In worldwide, rotavirus infection is Diarrhoea hospitalization most common reason (Parashar et al2003).Every day, estimated 1,205 children died from colyliform disease Poison disease.Due to rotavirus, having one in 5 children will seek medical advice, and have a needs hospitalization in 65 children, And about 293 children have a death of child.Death mostly occur in the Africa on the south the Indian subcontinent, the Sahara and South America (Parashar et al2003).

Rotavirus particle is to be formed by 3 layers of concentric albumen.Two kinds of albumen of virus outer layer, VP4 and VP7 and this disease Poison is relevant with the initial phase interaction of host cell.The projection (spikes) that VP4 formation extends from virion surface, and It is virus attachment polypeptide through being identified as, and VP7 is the calcium binding glucoprotein forming virion smooth surface, and be considered Relevant with postadhesion process (Mendez et al1999, Isa et al2006).Entering cell is a complicated process, its Including the interaction between virus outer layer albumen and cell surface molecule.In vivo, rotavirus is by intestinal villi Ripe enterocyte infects, and in vitro, rotavirus is attached in various cell line, but only some cell lines are felt Dye.Isa et al (2006) reports, and virus is mixed and disorderly with initial combination of cell surface, and attached after virus and specificity Between receptor the reason that interaction subsequently is cell entry cell.

Rotavirus ability based on they infection cells is divided into two types, this cell neuraminidase Process and remove sialic acid (N-acetyl-neuraminate) residue on host cell.Rotavirus from some animal needs thin Sialic acid residues on cellular surface adheres to, and other rotavirus of the many including Human reoviruslike agent strain is not gone up State needs.These Strain are known respectively as neuraminidase sensitivity (or relying on sialic) Strain and neuraminidase (or being independent of sialic) Strain (Isa et al, 2006) of resistance.It has been reported that claim, sialic acid derivative can Suppress susceptible and the virus of the susceptible cell of Human reoviruslike agent is not combined (Guo et al, 1999) to animal rotavirus. It has been reported that claim, the Ganglioside GM1 a of host cell surface works (Guo as receptor in Human reoviruslike agent infects et al,1999).It is reported, the neuraminidase resistance viral strain to neuraminic acid ferment treatment with resistance is capable of identify that tool There are internal sialic ganglioside (Delorme et al, 2001), this and the external residues combined in ganglioside Neuraminidase sensitive virus is contrasted (Isa et al, 2006).

It is reported, chemical compound lot (theaflavin, protease inhibitor, Yolk immunoglobulin, the sulphation saliva of synthesis Acid lipid (sialyl lipid) NMSO₃, human milk adhesion protein, MUCl mucin and cattle macromole lactalbumin (MMWP) portion Point) the internal rotavirus infection of external sum can be suppressed, but do not have compound to successfully use in clinic (Bojsen et al,2007;Peterson et al,2001;Takahashi et al,2002;Isa et al,2006)。 These work of major part are to use the zoosis strain of rotavirus rather than Human virus's strain to complete, such as MUC1 mucin and Cattle macromole whey fraction (Bojsen et al2007).Utilize by Fonterra Cooperative Group The Lactalbumin concentrate that Limited produces is studied, and this research shows utilizing rotavirus Murine Virus strain EDIM Mouse model in have the minimizing (Wolber et al, 2005) that rotavirus comes off.Kvistgaard et al, 2004 reports Road, Bovine Lactoferrin, Lac Bovis seu Bubali adhesion protein and cattle MUCl mucin can not prevent the rotavirus infection of vitro human Wa.

The general therapeutic of rotavirus diarrhea is rehydration therapy, but this therapy only treats symptom, and does not treat sense The reason of dye.Child is not the most recommended to use anti-diarrheal (Yung et al, 2005).

Therefore, treatment or the alternative medicine of prevention rotavirus infection are needed badly.Expect to provide for treating or preventing colyliform The viral alternative method infected or the selection that at least public is provided with.

Summary of the invention

Therefore, a first aspect of the present invention relates to treatment or one or more reagent of prevention rotavirus infection, This reagent is selected from:

Isomer, vaccenic acid or the combinations of the above of (a) one or more conjugated linoleic acids (CLA), or

The butterfat of (b) high CLA, the butterfat part of one or more high CLA, the hydrolysate of butterfat of high CLA, one or many The hydrolysate of the butterfat part of kind of high CLA or above-mentioned two or more combination any,

C () one or more butter fat compositionss, said composition is selected from

(i) butterfat, one or more butterfat part or combinations of the above,

(ii) anhydrous milkfat (AMF), one or more AMF part or above-mentioned two or more combination any,

(iii) one or more are rich in the part of the butterfat of phospholipid,

(iv) one or more are rich in the part of the butterfat of ganglioside,

One or more hydrolysates of any one or more of (v) (i) to (iv), and

(vi) two or more combination any of (i) to (v), or

Two or more combination any of (d) (a) to (c).

Another aspect of the present invention relates to treatment or one or more reagent of prevention rotavirus infection, this reagent It is selected from:

The butterfat of (b) high CLA, the butterfat part of one or more high CLA, the hydrolysate of butterfat of high CLA, one or many Plant hydrolysate or the combinations of the above of the butterfat part of high CLA,

The combination of (c) (a) and (b).

Another aspect of the present invention relates to treatment or prevention one or more reagent of rotavirus infection, and this reagent selects From:

(i) butter fat, one or more butterfat part or combinations of the above,

(ii) anhydrous butter fat (AMF), one or more AMF part or combinations of the above,

(iii) one or more are rich in the part of the butter fat of phospholipid,

(iv) one or more are rich in the part of the butter fat of ganglioside,

One or more hydrolysates of any one or more of (v) (i) to (iv), and

(vi) two or more combination any of (i) to (v).

Another aspect of the present invention relates to one or more reagent mentioned above in preparation for treating or preventing colyliform Purposes in the compositions that virus infects.

Another aspect of the present invention relates to the method treating or preventing rotavirus infection, and the method includes to needs one Or one or more reagent as described above of the individual effective dosage of multiple reagent as described above.

Embodiment hereafter can relate to any of above aspect.

In one embodiment, rotavirus is Human reoviruslike agent, i.e. infects the rotavirus strain of people.Real at another Executing in scheme, rotavirus is nonhuman rotavirus strain, such as birds (such as chicken, pigeon or turkey rotavirus strain), cattle, Dog, goat, horse, cat family, hare, Mus, sheep, pig or ape rotavirus strain.In one embodiment, rotavirus is neural Propylhomoserin enzyme sensitivity rotavirus.In another embodiment, rotavirus is neuraminidase resistance rotavirus.Still In another embodiment, rotavirus is the Human reoviruslike agent of neuraminidase resistance.Still in another embodiment In, neuraminidase resistance Human reoviruslike agent is Wa Human reoviruslike agent strain.In one embodiment, individuality is people.At one In embodiment, individual for adult, children or infants or the adult of immunocompromised host, children or infants.In another embodiment In, individuality is child, baby, the child of immunocompromised host or the baby of immunocompromised host.In another embodiment, individuality is for becoming People, the adult more than 55 years old, the adult of immunocompromised host, the adult more than 55 years old of immunocompromised host.

In one embodiment, the attachment of cell is treated or prevents rotavirus by reducing virus by described reagent Infect.In another embodiment, described reagent is treated by reducing cell entry cell or prevents rotavirus infection. In another embodiment, described reagent is treated by reducing the virus replication in cell or prevents rotavirus infection. In another embodiment, described reagent is treated by reducing the virus packaging in cell or prevents rotavirus infection. In another embodiment, described reagent is treated by reducing the cell cracking of virus or prevents rotavirus infection.? In one embodiment, described agent therapy or (diarrheagenic) rotavirus infection of prevention diarrhea inducing.Real at another Execute in scheme, the diarrhoea that described agent therapy or prevention rotavirus infection cause.

In one embodiment, the part rich in ganglioside comprises GD3 or GM3 or a combination thereof.

In one embodiment, the part rich in phospholipid comprise one or more PHOSPHATIDYL ETHANOLAMINE, one or more Phosphatidylinositols, one or more Phosphatidylserine, one or more phosphatidylcholines, one or more sphingolipids (include one Plant or multiple sphingomyelins, one or more dihydro sphingomyelins, one or more ceramides, one or more cerebroside or one Or multiple ganglioside or above-mentioned two or more combination in any any), one or more lysophosphatides (lose one The phospholipid of individual fatty acid) or above-mentioned two or more combination in any any.

In one embodiment, described reagent comprises one or more glyceride and (includes one or more glycerol mono-acid Ester, one or more diglyceride or one or more triglycerides or above-mentioned two or more any any Combination), one or more phospholipid (include one or more PHOSPHATIDYL ETHANOLAMINE, one or more phosphatidylinositols, one or many Plant Phosphatidylserine, one or more phosphatidylcholines, one or more sphingolipids (as described above) or above-mentioned any two Kind or more kinds of combination in any), one or more lysophosphatides (losing the phospholipid of a fatty acid), one or more are neural Amide, one or more ether phosphoglycerides, one or more cerebroside (include one or more glucosylceramides or One or more lactosylceramides or combinations of the above), one or more sulfatides or one or more gangliosides (include one or more monosialogangliosides, one or more bifunctional sialyltransferase gangliosides or one or more gather Sialic acid ganglioside or combinations of the above) or above-mentioned two or more combination in any any.

In one embodiment, described reagent is administered as the composition of lipid composition.Preferably iipidomic Compound includes animal, plant and marine products oil & fat and the lipid produced by fermentable.Preferably Animal fat bag Include but be not limited to fat of dairy product, particularly butter fat, including dilute butter.

In one embodiment, described reagent (generally passes through selected from dilute butter, butter, butter, anhydrous milkfat (AMF) The dehydration of the phase reversal of dilute butter or butter produces), buttermilk, butter serum (serum), β serum, one or more from separate Hard butterfat part (including H, SH and SSH part) that stage obtains, the soft butterfat portion obtained from the one or more stages separated Divide (including S, SS and SSS part), the combination of hard butterfat part, the combination of soft butterfat part, hard butterfat part and soft butterfat portion Point combination, glycosphingolipid fraction, part rich in butterfat ball (or " spherical ") membrane lipid (include, such as sphingolipid, ceramide and brain Glycosides fat), phospholipid moiety and complex lipid part, the butterfat rich in CLA, the butterfat part rich in CLA and above-mentioned any two kinds Or more kinds of combination in any, and above-mentioned hydrolysate, and the part of described hydrolysate, and hydrolyze and/or unhydrolysed portion The combination divided.These parts can obtain from any derivant of full milk or colostrum and full milk or colostrum, this full milk or colostrum Derivant include the dilute butter of dilute butter, sour cream and milk surum (the butterfat matter obtained from milk surum, the clear or cheese including yogurt Milk surum, preferred cheese milk surum).Sour cream is that full milk or the colostrum of preferably lactic acid bacteria fermentation obtain from acid-producing microorganisms Dilute butter.

In one embodiment, butterfat or its part are selected from dilute butter, butter, butter, anhydrous milkfat (AMF) (generally Produced by the dehydration of the phase reversal of dilute butter or butter), buttermilk, butter serum, β serum, from the one or more rank separated Hard butterfat part (including H, SH and SSH part) that section obtains, from the soft butterfat part that obtains of one or more stages separated (including S, SS and SSS part), the combination of hard butterfat part, the combination of soft butterfat part, hard butterfat part and soft butterfat part Combination and above-mentioned two or more combination in any any.

In one embodiment, AMF part selected from one or more hard butterfat parts (such as H, SH and SSH part), One or more soft butterfat parts (such as S, SS and SSS part), the combination of hard butterfat part, the combination of soft butterfat part, hard The combination of butterfat part and soft butterfat part and above-mentioned two or more combination in any any.

In one embodiment, rich in phospholipid part selected from buttermilk, one or more buttermilk parts, butter serum, One or more butter serum parts, β serum, one or more β serum part, one or more glycosphingolipid fraction, one or many Plant butterfat ball membrane lipid part, one or more phospholipid moieties, one or more complex lipid parts and above-mentioned any two kinds Or more kinds of combination in any.

In one embodiment, the part rich in ganglioside is selected from buttermilk, one or more buttermilk part, butter Serum, one or more butter serum parts, β serum, one or more β serum parts, one or more β serums rich in The part of GD3, the part rich in GM3 of one or more β serums, the part rich in GD3 and GM3 of one or more β serums And above-mentioned two or more combination in any any.

In certain embodiments, described part comprises:

The lipid of (a) about 5%w/w to about 100%w/w, or

The lipid of (b) about 40%w/w to about 100%w/w, or

The lipid of (c) about 5%w/w to about 95%w/w and the protein of about 0%w/w to about 75%w/w, or

The lipid of (d) about 15%w/w to about 95%w/w and the protein of about 0%w/w to about 75%w/w, or

E () about 5%w/w is to the lipid of about 95%w/w, about 0%w/w to the protein of about 75%w/w, about 5%w/w to about 85%w/ The phospholipid of w and the ganglioside of about 0%w/w to about 5%w/w, or

F () about 15%w/w is to the lipid of about 95%w/w, about 0%w/w to the protein of about 65%w/w, about 5%w/w to about 70% The phospholipid of w/w and the ganglioside of about 0%w/w to about 2.5%w/w.

In certain embodiments, described part comprise at least about 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90% or the phospholipid of 95%w/w, and can be between arbitrarily these values Select available scope (such as, about 5%w/w to about 95%w/w, about 10%w/w to about 95%w/w, about 15%w/w to about 95%w/w, About 20%w/w to about 95%w/w, about 25%w/w to about 95%w/w, about 30%w/w to about 95%w/w, about 35%w/w to about 95%w/w, About 40%w/w to about 95%w/w, about 45%w/w to about 95%w/w, about 50%w/w to about 95%w/w, about 10%w/w to about 70%w/w, About 15%w/w to about 70%w/w, about 20%w/w to about 70%w/w, about 25%w/w to about 70%w/w, about 30%w/w to about 70%w/w, About 35%w/w is to about 70%w/w, about 40%w/w to about 70%w/w, about 45%w/w to about 70%w/w and about 50%w/w to about 70%w/w Phospholipid).

In certain embodiments, described part comprise at least about 0.1%, 0.5%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%、10%、11%、12%、13%、14%、15%、16%、17%、18%、19%、20%、21%、22%、23%、24%、25%、26%、27%、 28%, 29% or 30%w/w independently selected from phosphatidylcholine, PHOSPHATIDYL ETHANOLAMINE, sphingomyelins, Phosphatidylserine and phospholipid One or more phospholipid of acyl inositol, and (e.g., from about 0.1%w/w is to about can to select the scope that can use between arbitrarily these values 30%w/w, about 0.5%w/w are to about 30%w/w, about 1%w/w to about 30%w/w, about 2%w/w to about 30%w/w, about 3%w/w to about 30% W/w, about 4%w/w are to about 30%w/w, about 5%w/w to about 30%w/w, about 10%w/w to about 30%w/w, about 15%w/w to about 30%w/ W, about 20%w/w to about 30%w/w, about 0.1%w/w to about 5%w/w, about 0.5%w/w to about 5%w/w, about 1%w/w to about 5%w/w, About 2%w/w is to about 5%w/w, about 3%w/w to about 5%w/w, about 0.1%w/w to about 10%w/w, about 0.5%w/w to about 10%w/w, about 1%w/w is to about 10%w/w, about 2%w/w to about 10%w/w, about 3%w/w to about 10%w/w, about 4%w/w to about 10%w/w, about 5%w/ W is to about 10%w/w, about 6%w/w to about 10%w/w, about 0.1%w/w to about 20%w/w, about 0.5%w/w to about 20%w/w, about 1%w/w To about 20%w/w, about 2%w/w to about 20%w/w, about 3%w/w to about 20%w/w, about 4%w/w to about 20%w/w, about 5%w/w to about 20%w/w, about 10%w/w to about 20%w/w, about 15%w/w to about 20%w/w independently selected from phosphatidylcholine, phosphatidyl ethanol One or more phospholipid of amine, sphingomyelins, Phosphatidylserine and phosphatidylinositols).

In certain embodiments, described part comprises:

A () about 25%w/w is to the protein of about 35%w/w, about 15%w/w to the lipid of about 25%w/w and about 5%w/w to about The phospholipid of 12%w/w, or

B () about 25%w/w is to the protein of about 35%w/w, about 15%w/w to the lipid of about 25%w/w, about 5%w/w to about 12% The phospholipid of w/w, about 5%w/w to the MFGM albumen of about 10%w/w and the ganglioside of about 0.2%w/w to about 0.9%w/w, or

C () about 25%w/w is to the protein of about 35%w/w, about 15%w/w to the lipid of about 25%w/w, about 5%w/w to about 12% The phospholipid of w/w, about 1%w/w to the phosphatidylcholine of about 5%w/w, about 1.5%w/w to the PHOSPHATIDYL ETHANOLAMINE of about 6%w/w, about 1% W/w is to the sphingomyelins of about 5%w/w, about 0.5%w/w to the phospholipid of the Phosphatidylserine of about 2%w/w, about 0.1%w/w to 2%w/w Acyl inositol, about 5%w/w to the MFGM albumen of about 10%w/w and the ganglioside of about 0.2%w/w to about 0.9%w/w, or

D () about 40%w/w is to the protein of about 60%w/w, about 25%w/w to the lipid of about 45%w/w and about 10%w/w to about The phospholipid of 25%w/w, or

E () about 40%w/w is to the protein of about 60%w/w, about 25%w/w to the lipid of about 45%w/w, about 10%w/w to about The phospholipid of 25%w/w, about 5%w/w to the MFGM albumen of about 20%w/w and the ganglioside of about 0.5%w/w to about 2.0%w/w, or

F () about 46%w/w is to the protein of about 52%w/w, about 28%w/w to the lipid of about 40%w/w, about 11%w/w to about The phospholipid of 16%w/w, about 2%w/w are to the phosphatidylcholine of about 6%w/w, about 3%w/w to the PHOSPHATIDYL ETHANOLAMINE of about 8%w/w, about 2.5%w/w is to the sphingomyelins of about 7%w/w, about 0.5%w/w to the Phosphatidylserine of about 3%w/w, about 0.5%w/w to 2%w/w Phosphatidylinositols, about 5%w/w to the MFGM albumen of about 15%w/w and the ganglioside of about 0.5%w/w to about 0.9%w/w, or

G () about 50%w/w is to the protein of about 70%w/w, about 12%w/w to the lipid of about 32%w/w and about 5%w/w to about The phospholipid of 25%w/w, or

H () about 50%w/w is to the protein of about 70%w/w, about 12%w/w to the lipid of about 32%w/w, about 5%w/w to about 25% The phospholipid of w/w, about 2%w/w are to the phosphatidylcholine of about 8%w/w, about 2%w/w to the PHOSPHATIDYL ETHANOLAMINE of about 10%w/w, about 2%w/ The sphingomyelins of w to about 8%w/w and about 1%w/w are to the Phosphatidylserine of about 3%w/w, about 10%w/w to the MFGM egg of about 20%w/w The white ganglioside with about 0.5%w/w to about 2.5%w/w, or

The protein of (i) about 56%w/w to about 65%w/w, about 18% to the lipid of about 28%w/w, about 8%w/w to about 20%w/w Phospholipid, about 2%w/w to the phosphatidylcholine of about 8%w/w, about 2%w/w to the PHOSPHATIDYL ETHANOLAMINE of about 10%w/w, about 2%w/w extremely The sphingomyelins of about 8%w/w and the Phosphatidylserine of about 1%w/w to about 3%w/w and the phosphatidyl-4 of about 0.5%w/w to 3%w/w Alcohol, about 10%w/w to the MFGM albumen of about 20%w/w and about 0.5%w/w to about 2.5%w/w ganglioside, or

J () about 0%w/w is to the protein of about 10%w/w, about 85%w/w to the lipid of about 97%w/w and about 25%w/w to about The phospholipid of 35%w/w, or

K () about 0%w/w is to the protein of about 10%w/w, about 85%w/w to the lipid of about 97%w/w, about 25%w/w to about 35% The phospholipid of w/w, about 5%w/w to the phosphatidylcholine of about 10%w/w, about 7%w/w to the PHOSPHATIDYL ETHANOLAMINE of about 13%w/w, about 4% W/w is to the sphingomyelins of about 9%w/w, about 2%w/w to the Phosphatidylserine of about 5%w/w, about 1%w/w to the phosphatidyl of about 3%w/w Inositol, about 0%w/w to the MFGM albumen of about 5%w/w and the ganglioside of about 1%w/w to about 3%w/w, or

L () about 10% is to the protein of about 15%w/w, about 80%w/w to the lipid of about 95%w/w and about 60%w/w to about 80% The phospholipid of w/w, or

M () about 10%w/w is to the protein of about 15%w/w, about 80%w/w to the lipid of about 95%w/w, about 60%w/w to about The phospholipid of 80%w/w, about 10%w/w to the phosphatidylcholine of about 20%w/w, about 18%w/w to the PHOSPHATIDYL ETHANOLAMINE of about 28%w/w, About 10%w/w is to the sphingomyelins of about 20%w/w, about 4%w/w to the Phosphatidylserine of about 12%w/w, about 2%w/w to about 10%w/w Phosphatidylinositols, the MFGM albumen of about 0%w/w to about 5%w/w and the ganglioside of about 1%w/w to about 5%w/w, or

The lipid of (n) about 75%w/w to about 99%w/w and the phospholipid of about 15%w/w to 35%w/w, or

O () about 80%w/w is to the lipid of about 90%w/w, about 5%w/w to the phosphatidylcholine of about 15%w/w, about 5%w/w to about The PHOSPHATIDYL ETHANOLAMINE of 15%w/w, about 4%w/w are to the sphingomyelins of about 10%w/w and about 0.1%w/w to about 2%w/w phosphatidyl silk ammonia Acid, or

P () about 80%w/w is to the phospholipid of the lipid of about 90%w/w, about 20%w/w to 30%w/w, about 5%w/w to about 15%w/w Phosphatidylcholine, the sphingomyelins of about 5%w/w to the PHOSPHATIDYL ETHANOLAMINE of about 15%w/w, about 5%w/w to about 10%w/w, about 0.5% The Phosphatidylserine of w/w to about 1.5%w/w and the phosphatidylinositols of about 0.1%w/w to about 1.2%w/w, or

The lipid of (q) about 75%w/w to about 95%w/w and the phospholipid of about 50%w/w to about 90%w/w, or

The lipid of (r) about 80%w/w to about 90%w/w, about 10% to the phosphatidylcholine of about 30%w/w, about 12%w/w to about The PHOSPHATIDYL ETHANOLAMINE of 22%w/w, about 12%w/w are to the phosphatidyl silk ammonia of the sphingomyelins of about 22%w/w and about 1%w/w to about 3%w/w Acid, or

S () about 75%w/w is to the lipid of about 95%w/w, about 50%w/w to the phospholipid of about 90%w/w, about 10%w/w to about 45% The phosphatidylcholine of w/w, about 12%w/w to the PHOSPHATIDYL ETHANOLAMINE of about 25%w/w, the sphingomyelins of about 12% to about 25%w/w, about 1% The Phosphatidylserine of w/w to about 6%w/w and the phosphatidylinositols of about 0.5%w/w to 4%w/w, or

T () about 80%w/w is to the lipid of about 90%w/w, about 65%w/w to the phospholipid of about 75%w/w, about 10%w/w to about 30% The phosphatidylcholine of w/w, about 12%w/w to the PHOSPHATIDYL ETHANOLAMINE of about 22%w/w, about 12%w/w to the sphingomyelins of about 22%w/w, The Phosphatidylserine of about 1%w/w to about 3%w/w and the phosphatidylinositols of about 0.5%w/w to 3%w/w, or

The lipid of (u) about 25%w/w to about 45%w/w and the Ganglioside, GD3 of about 0.2%w/w to about 1%w/w, or

V () about 25%w/w is to the lipid of about 45%w/w, about 10%w/w to the phospholipid of about 30%w/w and about 0.2%w/w to about 1% The ganglioside of w/w, or

W () about 25%w/w is to the lipid of about 45%w/w, about 10%w/w to the phospholipid of about 30%w/w, about 2%w/w to about 5%w/w Phosphatidylcholine, about 3%w/w to the PHOSPHATIDYL ETHANOLAMINE of about 7%w/w, about 2%w/w is to the sphingomyelins of about 5%w/w, about 2%w/w To the Phosphatidylserine of about 12%w/w, about 1%w/w to the phosphatidylinositols of about 5%w/w and the god of about 0.2%w/w to about 1%w/w Warp knuckle glycosides fat, or

The lipid of (x) about 20%w/w to about 40%w/w and about 0.8%w/w to about 2%w/w Ganglioside, GD3, or

Y () about 20%w/w is to the lipid of about 40%w/w, about 5%w/w to the phospholipid of about 30%w/w and about 0.8%w/w to about The ganglioside of 3.5%w/w, or

Z () about 20%w/w is to the lipid of about 40%w/w, about 5%w/w to the phospholipid of about 30%w/w, about 1%w/w to about 5%w/w Phosphatidylcholine, about 2%w/w to the PHOSPHATIDYL ETHANOLAMINE of about 8%w/w, about 0.5%w/w is to the sphingomyelins of about 5%w/w, about 1%w/ W is to the Phosphatidylserine of about 10%w/w, about 1%w/w to the phosphatidylinositols of about 6%w/w and about 0.8%w/w to about 3.5%w/w Ganglioside.

In one embodiment, described part comprise at least about 70% TL, the phosphatidylcholine of at least about 12%, PHOSPHATIDYL ETHANOLAMINE, the sphingomyelins of at least about 6% and the Phosphatidylserine of at least about 1% of at least about 6%.This embodiment party In the preferred part of case, described part comprise about 1.8% butanoic acid (4:0), the capric acid (10:0) of about 0.3%, the Laurel of about 0.5% Acid (12:0), the myristic acid (14:0) of about 7.4%, the myristoleic acid (14:1) of about 14.1%, the pentadecanoic acid of about 1.0% (15:0), about 26.0% Palmic acid (16:0), the palmitoleic acid (16:1) of about 1.7%, the heptadecanoic acid (17:0) of about 0.6%, about The heptadecenoic acid (17:1) of 0.3%, the stearic acid (18:0) of about 11.9%, the oleic acid (18:1) of about 39.0%, the sub-oil of about 5.0% Acid (18:2), the linolenic acid (18:3) of about 2.0%, the arachidic acid (20:0) of about 0.3% and the cholesterol of about 0.8%.The most real Execute in scheme, the fatty acid of this part composition substantially Phospholipid as described in Examples below Concentrate (phospholipid concentrate) PC500^TMPhospholipid moiety.Or, described part is the hydrolysis of the part of this embodiment Thing.

In another embodiment, described part comprises the TL of at least about 80%, the phosphatidyl gallbladder of at least about 30% The sphingomyelins of the PHOSPHATIDYL ETHANOLAMINE of alkali, at least about 6%, at least about 15% and the Phosphatidylserine of at least about 2%.Real at this In the preferred part of scheme of executing, described part comprise about 6.6% myristic acid (14:0), the Palmic acid (16:0) of about 27.0%, The palmitoleic acid (16:1) of about 1.3%, the heptadecanoic acid (17:0) of about 2.3%, the stearic acid (18:0) of about 14%, the oil of about 38.0% Acid (18:1), the linoleic acid (18:2) of about 6.5%, about 2.0% linoleic acid (18:3) and the cholesterol of about 0.1%.Preferably implementing In scheme, the fatty acid of this part composition substantially Phospholipid as described in Examples below Concentrate PC600^TMOr PC700^TMPhospholipid moiety.Or, described part is the hydrolysis of the part of this embodiment Thing.

In one embodiment, described part comprises TL, the ganglioside of at least about 0.5% of at least about 30% Fat GD3 and the Ganglioside GM3 of at least about 0.4%.In preferred embodiments, the fatty acid composition of this part is basic Upper G500 as described in examples below^TMGanglioside moieties.Or, described part is hydrolysate.

In another embodiment, described part comprises TL, the ganglioside of at least about 1.2% of at least about 30% Fat GD3 and the Ganglioside GM3 of at least about 0.2%.In preferred embodiments, the fatty acid composition of this part is basic Upper Ganglioside (ganglioside) G600 as described in examples below^TMGanglioside moieties.Or, described Part is the hydrolysate of this embodiment part.

In one embodiment, compositions useful herein comprises at least about 0.1%, 0.2%, 0.5%, 1%, 5%, 10%、15%、20%、25%、30%、35%、40%、45%、50%、55%、60%、65%、70%、75%、80%、85%、90%、95%、99%、 99.5%, one or more reagent mentioned above of 99.8% or 99.9% weight ratio, or compositions base useful in the present invention It is made up of mentioned reagent on Ben, or is made up of mentioned reagent, and the scope that can use can be selected between arbitrarily these aforementioned value (such as, about 0.1% to about 50%, about 0.2% to about 50%, about 0.5% to about 50%, about 1% to about 50%, about 5% to about 50%, about 10% To about 50%, about 15% to about 50%, about 20% to about 50%, about 25% to about 50%, about 30% to about 50%, about 35% to about 50%, about 40% to about 50%, about 45% to about 50%, about 0.1% to about 60%, about 0.2% to about 60%, about 0.5% to about 60%, about 1% to about 60%, about 5% to about 60%, about 10% to about 60%, about 15% to about 60%, about 20% to about 60%, about 25% to about 60%, about 30% to about 60%, about 35% to about 60%, about 40% to about 60%, about 45% to about 60%, about 0.1% to about 70%, about 0.2% to about 70%, about 0.5% To about 70%, about 1% to about 70%, about 5% to about 70%, about 10% to about 70%, about 15% to about 70%, about 20% to about 70%, about 25% To about 70%, about 30% to about 70%, about 35% to about 70%, about 40% to about 70%, about 45% to about 70%, about 0.1% to about 80%, about 0.2% to about 80%, about 0.5% to about 80%, about 1% to about 80%, about 5% to about 80%, about 10% to about 80%, about 15% to about 80%, About 20% to about 80%, about 25% to about 80%, about 30% to about 80%, about 35% to about 80%, about 40% to about 80%, about 45% to about 80%, about 0.1% to about 90%, about 0.2% to about 90%, about 0.5% to about 90%, about 1% to about 90%, about 5% to about 90%, about 10% to About 90%, about 15% are to about 90%, about 20% to about 90%, about 25% to about 90%, about 30% to about 90%, about 35% to about 90%, about 40% To about 90%, about 45% to about 90%, about 0.1% to about 99%, about 0.2% to about 99%, about 0.5% to about 99%, about 1% to about 99%, about 5% to about 99%, about 10% to about 99%, about 15% to about 99%, about 20% to about 99%, about 25% to about 99%, about 30% to about 99%, about 35% to about 99%, about 40% to about 99% and about 45% to about 99%).

In one embodiment, compositions useful herein comprise at least about 0.001 gram, 0.01 gram, 0.05 gram, 0.1 gram, 0.15 gram, 0.2 gram, 0.3 gram, 0.4 gram, 0.5 gram, 1 gram, 2 grams, 3 grams, 4 grams, 5 grams, 6 grams, 7 grams, 8 grams, 9 grams, 10 Gram, 11 grams, 12 grams, 13 grams, 14 grams, 15 grams, 16 grams, 17 grams, 18 grams or one or more reagent mentioned above of 19 grams, or Compositions useful in the person present invention is substantially made up of mentioned reagent, or is made up of mentioned reagent, and can arbitrarily these The scope (such as, about 0.01 gram to about 1 gram, about 0.01 gram to about 10 gram, about 0.01 gram to about 19 that can use is selected between aforementioned value Gram, about 0.1 gram to about 1 gram, about 0.1 gram to about 10 gram, about 0.1 gram to about 19 gram, about 1 gram to about 5 gram, about 1 gram to about 10 gram, About 1 gram to about 19 grams, about 5 grams to about 10 grams and about 5 grams to about 19 grams).

In one embodiment, compositions useful herein comprises about 0.1%, 0.5%, 1%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 97%, 99% or 99.9% weight Measure fresh whole milk or the breast derivant of ratio, or compositions useful herein is substantially made up of mentioned reagent, or by above-mentioned Reagent forms, and can select to can use between arbitrarily these aforementioned value scope (such as, about 0.1% to about 50%, about 0.2% to About 50%, about 0.5% to about 50%, about 1% to about 50%, about 5% to about 50%, about 10% to about 50%, about 15% to about 50%, about 20% to About 50%, about 25% are to about 50%, about 30% to about 50%, about 35% to about 50%, about 40% to about 50% and about 45% to about 50%).Institute State breast derivant and preferably be selected from regeneration, powder or fresh skimmed milk, regenerate or the whole milk powder that reduces or skimmed milk powder, skimmed milk Concentrate, skimmed milk retentate (retentate), concentrate breast, ultrafiltration breast retentate, lactoprotein concentrate (MPC), lactoprotein divides From thing (MPI), decalcification lactoprotein concentrate (MPC), low fat milk, low fat milk protein concentrate (MPC), casein, caseinic acid Salt, butterfat, dilute butter, butter, butter, anhydrous milkfat (AMF), buttermilk, butter serum, β serum, hard butterfat part, soft butterfat Part, glycosphingolipid fraction, butterfat ball film part, butterfat ball membrane lipid part, phospholipid moiety, complex lipid part, colostrum, colostrum Part, colostrum protein concentrate (CPC), colostrum whey, from the immunoglobulin part of colostrum, milk surum (includes sweet whey, breast Yogurt is clear, mineral acid whey or the whey powder of reduction), lactalbumin isolate (WPI), Lactalbumin concentrate (WPC), be derived from Arbitrarily breast or colostrum processes the compositions flowing (processing stream), is derived from by surpassing that arbitrarily breast or colostrum processing are flowed Retentate that filter or microfiltration obtain or the compositions of penetrant (permeate), be derived from by arbitrarily breast or colostrum processing stream Chromatograph (including but not limited to ion and gel permeation chromatography) separate obtain penetrate or the compositions of absorbed portion, including leading to Cross multiple stage separation, difference crystallization (differential crystallisation), solvent separates, supercritical separates, near critical Separate, distillation, centrifugation or use the extract separating preparation of modifying agent (such as soap or emulsifying agent) interior any this The extract of a little breast derivants, the arbitrarily hydrolysate of these derivants, the part of hydrolysate and include hydrolysis and/or do not hydrolyze The combination of part is in the combination in any of interior two or more these derivants any.Should be appreciated that coming of these derivants Source can be breast or colostrum or a combination thereof.

In one embodiment, compositions useful herein also comprises pharmaceutically acceptable carrier.Real at another Executing in scheme, described compositions is or is configured to food, beverage, food additive, beverage additive, supplementary, battalion The product of supporting, medicated food, nutrition product, parenteral feed product, generation meal, cosmeceutical, health product, medicine Or medicine (pharmaceutical) (medicament).In one embodiment, the form of described compositions is tablet, capsule Sheet (caplet), pill, hard or soft capsule or lozenge.In one embodiment, the form of described compositions is sachet Agent, powder, assignable powder (dispensable powder), granule, suspension, elixir, liquid maybe can join Other form any in Foods or drinks, including such as water, breast or fruit juice.In one embodiment, described compositions is also wrapped Containing one or more components (such as antioxidant), this component can during storing or after being administered during avoid or reduce The degraded of described compositions.These compositionss may be configured to carry any edible consumer goods of lipid.The most edible Include water-based product, bakery, the pan work including chocolate, gel, ice cream with the example of consumer goods, go back Former fruit product, snack bar (snack bar), food bars (food bar), muesli bar (muesli bar), it is coated with Smearing food (spread), sauce, dipping liquid (dip), the milk product including Yoghurt and cheese, including based on milk and base In the beverage of non-dairy at interior beverage, breast, milk powder, include based on the fortune including milk and sports supplement based on non-dairy Dynamic supplement, fruit juice, such as albumen dispenses the food additive of microgranule (protein sprinkle), including supplement day tablet, Ablactational food and Yoghurt are at interior nutritional supplementation goods and powder or the such as infant formula of liquid form (formula), bigger infant formula (follow-on formula) or the milk replacer of growth milk replacer.The shape that can be similar to Formula provides suitable Halth-care composition useful herein.

In one embodiment, described compositions can also comprise antiviral agent, or reagent can be with antiviral agent group Close, be selected from the sulphation sialic acid lipid NMSO of theaflavin, protease inhibitor, Yolk immunoglobulin, synthesis₃, people Breast adhesion protein (glycoprotein of butterfat ball film), MUC1 mucin, cattle macromole whey fraction or the one of combinations of the above Plant or multiple antiviral agent.In one embodiment, compositions useful herein includes breast component, or by said composition Being administered simultaneously or sequentially with breast component, this breast component such as lactalbumin, whey fraction (include acidity or alkalescence milk surum egg White part or a combination thereof), PROVON 190, lactoferrin, ferrum-lactoferrin, functional lactoferrin or ferrum-Lactoferrtin variants, Functional lactoferrin or ferrum-lactoferrin fragment, vitamin D or calcium or above-mentioned any two or more kinds of any group Close.Preferably, said composition can also comprise lactoferrin, ferrum-lactoferrin, functional lactoferrin or ferrum-lactoferrin Variant, functional lactoferrin or ferrum-lactoferrin fragment or above-mentioned two or more combination any, or reagent can With combination of the above.

Quoting to also aim to comprise whole in the range of this had digital scope disclosed herein (such as, 1 to 10) Reason number (such as, 1,1.1,2,3,3.9,4,5,6,6.5,7,8,9 and 10), and any range (example of rational number in the range of this As, 2 to 8,1.5 to 5.5 and 3.1 to 4.7) quote, therefore, specifically disclose explicitly disclosed herein whole herein Whole subranges of scope.Only enumerate and there is specifically intended example, and think the most clearly Indicate the whole possible combination of numerical value between cited minima and maximum.

In this manual, when referenced patents description, other external file or out of Memory are originated, this be typically be The purpose of context is provided for discussing inventive feature.Except as otherwise noted, otherwise these external files are quoted not It is understood to that these sources recognizing these files or information are prior aries in any authority, or forms this area Common knowledge part.

Accompanying drawing is sketched

Two pictures of Fig. 1 represent, according to embodiment 2, use (A) high CLA butterfat or (B) from Fonterra Co- The G600 of the butterfat that operative Group Limited buys^TMGanglioside moieties process animal in the most infected The percentage rate of cell.

Detailed Description Of The Invention

Examples below proves, is prevented the cell attachment of rotavirus by various butterfat parts in vitro, and proves Butterfat part is treated or the ability of pre-anti-diarrhea in the animal model having infected Wa Human reoviruslike agent strain.

1. definition

Term " anhydrous milkfat " and " AMF " are used interchangeably herein, and mean the phase reversal by dilute butter or The butterfat part that the dehydration of butter almost entirely removes water and non-fat material and prepares.AMF is (if there is additive Words, also referred to as " anhydrous milk fat (anhydrous butteroil) ") generally make from the dilute butter coming from full milk or butter Standby, but can also prepare from first Ruzhong.Bylund (Ed., 1995) discloses the common method preparing AMF, this list of references Intactly it is incorporated to herein.Preferably AMF is typically about 60%, about 70%, about 80%, about 90%, about 95%, greater than about 95%, about 96%, about 97%, about 98%, about 99%, about 99.5% or the lipid of 100%, and there is the lipid of about 98% to about 100%, particularly The AMF of lipid, 99.5% lipid or the higher lipid of about 99% is preferred.For AMF or anhydrous milk fat, alimentary codex leads to Often require the moisture less than 0.2%, and for butter oil, alimentary codex usually requires that the moisture less than 0.7%.Generally AMF is entered One step is separated into " firmly " (H) and " soft " (S) part, additionally it is possible to " soft " (S) part is further separated into " soft or hard (soft Hard) " (SH) and " soft (soft soft) " (SS) part, it is possible to by soft (soft soft) " (SS) part is further It is separated into " soft or hard (soft soft hard) " (SSH) and " soft soft (soft soft soft) " (SSS) part.Should manage Solving, the fatty acid composition of every kind of part is different.The non-limiting example fatty acid composition of AMF and derivative moiety is shown in hereafter Table 1 to table 5 in.

The exemplary AMF of table 1. forms

The exemplary hard portion of table 2. (part H) forms

Table 3. exemplary soft or hard part (part SH) forms

Table 4. exemplary soft or hard part (part SSH) forms

The exemplary soft soft part (part SSS) of table 5. forms

Term " β-serum " represents the aqueous dairy component from the milk flow separation containing the fat more than 60%, as hereafter Described, this separation is by realizing from the phase reversal of O/w emulsion to water-in-oil emulsion.Dilute butter is for preparing β-breast The preferred raw material of slurry.Such as, as shown in Fig. 2 in WO2006/041316, (the most anhydrous preparing butter oil from dilute butter Butterfat or AMF) during prepare β-serum.Preferably, β serum is dried；Preferably, the β-serum being dried is powder.

Term " butterfat of high CLA " is used interchangeably with term " rich in the butterfat of CLA ", and represents butterfat, this butterfat Comprise higher levels of cis-9, trans-11CLA or its salt, ester or precursor than common butterfat, and optionally comprise higher levels of One or more other CLA isomers.Butterfat rich in CLA can be prepared by known technology, this technology include but not The supplementary of free fatty being limited to pasture breeding milk cow feeds, and such as, feeds according to known method fish oil and sunflower oil Milch cow.Generally prepare the butterfat rich in CLA from full milk but it also may prepare from colostrum.Disclosed international pct application WO2005/ Describing the usual compositions of the butterfat rich in CLA in 107736, this application is merged in herein by quoting.Rich in CLA's Butterfat can also be by supplementing butterfat with CLA and prepare as mentioned below.In one embodiment, rich in the butterfat of CLA Comprise the CLA of at least about 2%, 4%, 6%, 8%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45% or 50% weight ratio, the most cis- 9, trans-11CLA, or its salt, ester or precursor, and the scope (e.g., from about 4% that can use can be selected between arbitrarily these aforementioned value To about 7%).Cis-9, the trans-11CLA of at least about 2% weight ratio, preferably from about 2% to 10% weight is preferably comprised rich in the butterfat of CLA Cis-9, the trans-11CLA of amount ratio, cis-9, the trans-11CLA of more preferably from about 4% to 7% weight ratio, and most preferably from about 5% weight ratio Cis-9, trans-11CLA.In one embodiment, the butterfat rich in CLA comprises CLA isomer, and this isomer comprises at least The CLA of about 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% or 99% weight ratio, the most cis-9, trans-11CLA or Its salt, ester or precursor, and the scope (e.g., from about 80% to about 95%) that can use can be selected between arbitrarily these aforementioned value.Rich in The butterfat of CLA preferably comprises CLA isomer, and this isomer comprises cis-9, the trans-11CLA of at least about 50% weight ratio, preferably Cis-9, the trans-11CLA of about 70% to 80% weight ratio.

In this specification term used " comprise " expressions " at least in part by ... form ".When explaining in present specification During including the narration of this term, all must exist with the feature that this term is initial in each narration or claim, but its Its feature can also exist.Such as " comprise (comprise) " and the relational language of " comprising (comprised) " in the same manner Explain.

Term " conjugated linoleic acid " (CLA) represents one or more CLA isomers, and this isomer is selected from free or esterification shape The 9 of formula, 11-octadecadienoic acid and 10,12-octadecadienoic acid, or its salt, or its mixture, this isomer include cis-9, Cis-11, cis-9, trans-11, trans-9, cis-11, trans-9, trans-11, cis-10, cis-12, cis-10, trans-12, trans-10, cis-12 and Trans-10, anti-12 isomers, the most cis-9, cis-11, cis-9, trans-11, trans-10, cis-12 and cis-10, cis-12 isomers, as In disclosed United States Patent (USP) US5, described in 585,400, this patent is merged in herein by quoting.Chin et al(1992) Describing the most cis-9, the CLA natural origin of trans-11CLA, this natural origin includes animal, antibacterial and plant origin.Can lead to Linoleic acid is become CLA by the fermentation crossing following antibacterial: such as, produces brood cell clostridium (Clostridium Sporogenes), Clostridium bifermentans (Clostridium bifermentans), mud clostridium (Clostridium sordellii) and bacteroid (Bacteroides sp) (Verhulst, et al., 1985).Other is used Organism in bacterial fermentation includes Butyrivibrio fibrisolvens (Butyrivibrio fibrisolvens), eubacterium lentum (Eubacterium lentum), propionibacterium freudenreichii (Propionibacterium freudenreichi), bacillus acidophilus (Lactobacillus acidophilus), Lactobacillus reuteri (Lactobacillus reuteri), Erichsen megacoccus (Megasphaera elsdenii) and bifidobacterium breve (Bifidobacterium breve).Contain about 65% and 76% respectively Linoleic sunflower oil Flos Carthami oil may be used for the preparation of CLA.

" effective dose " is to confer to the amount required for therapeutic effect.Freireich et al. (1966) describes animal and people's Dosage mutual relation (based on milli gram/m surface).Body surface area can be about determined from individual height and body weight.Ginseng See, such as Scientific Tables (science tabulation), Geigy Pharmaceuticals, Ardley, New York, 1970,537.As understood by those skilled in the art, effective dosage becomes also as route of administration, the use etc. of carrier Change.

Term " rich in (enrich) " and " rich in (enriched) " represent the appointment composition that part or compositions are had Concentration come than in full milk, dilute butter, butter, anhydrous milkfat, buttermilk, butter serum or β serum or described part or compositions The concentration specifying composition present in female part (parent fraction) in source is high.Such as rich in the part of ganglioside Have than full milk, dilute butter, butter, anhydrous milkfat, buttermilk, butter serum or the higher ganglioside concentrations of β serum Part.Similarly, the part rich in phospholipid is to have than full milk, dilute butter, butter, anhydrous milkfat, buttermilk, butter serum or β The part of the higher phospholipid concentration of serum.

Term " part " represents the compositions separated from source material, and said composition with isolate described part Source material composition difference.Such as, non-human mammal butterfat part, such as sheep, goat, pig, Mus, Babalus bubalis L., camel, yak Cattle, horse, donkey, yamma or butter fat part, preferably butter fat part, be not with the composition of the naturally occurring butterfat in full milk With.In selectable embodiment, the concentration in described part is higher than full milk, or full colostrum, or the dilute milk from breast Oil, or the dilute butter from colostrum, or the AMF from breast, or from the concentration in the AMF of colostrum.Useful herein is preferred Source material includes full milk, dilute butter, anhydrous milkfat, buttermilk, butter serum or β serum or the dilute butter of milk surum from Lac Bovis seu Bubali. As described herein, it is preferred to part be lipid part.

Therefore, term " rich in the butterfat part of phospholipid " represents the separate section of non-human mammal butterfat, wherein this portion The phospholipid concentration divided is higher than the phospholipid concentration of naturally occurring non-human mammal butterfat.Preferably, part useful herein In at least one phospholipid, or the concentration of at least one phospholipid and at least one ganglioside moves than naturally occurring inhuman suckling Concentration in thing butterfat up at least about 0.5%, 1%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% or 100%, and the scope that can use can be selected between these values.Optional In the embodiment selected, the concentration in described part is higher than full milk, or full colostrum, or the dilute butter from breast, or from colostrum Dilute butter, or the AMF from breast, or from the concentration in the AMF of colostrum.

Similarly, term " rich in the butterfat part of ganglioside " represents the separate section of non-human mammal butterfat, Wherein the ganglioside concentrations of this part is higher than the phospholipid concentration of naturally occurring non-human mammal butterfat.Preferably, originally At least one ganglioside in part useful in literary composition, or the concentration ratio of at least one ganglioside and at least one phospholipid Concentration in naturally occurring non-human mammal butterfat up at least about 0.5%, 1%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95 or 100%, and can select between these values The scope of effect.In selectable embodiment, the concentration in described part is higher than full milk, or full colostrum, or dilute from breast Butter, or the dilute butter from colostrum, or the AMF from breast, or from the concentration in the AMF of colostrum.

Term " functional lactoferrin fragment " is intended to indicate that naturally occurring or non-naturally-occurring of lactoferrin polypeptide Part, when measuring according to Examples below, this part is active and includes metal ion functional fragment.Useful newborn ferrum Protein fragments includes the lactoferrin polypeptide of truncate, the metal ion of lactoferrin combines hydrolysate, comprise N-lobule (lobe) The fragment of metal ion binding pocket (binding pocket), the fragment comprising C-lobule metal ion binding pocket and (pass through Artificial or natural process) the metal ion binding fragment identified of the known technology that is generated by being discussed below.Disclosed international Patent application WO2006/054908 and WO2007/043900 reports preparation and the purposes of lactoferrin fragment, each application It is merged in herein by quoting.

Term " functional lactoferrin variant " is intended to indicate that newborn ferrum egg active when measuring according to examples below The variant of white polypeptide, and include metal ion functional variant.

Term " lactoferrin polypeptide " means non-glycosylated or glycosylated wild type lactoferrin aminoacid sequence or comes From the homology lactoferrin sequence of such as those described below species.Lactoferrin polypeptide has two metal ions and combines Bag, therefore can carry out bind metal ion according to the stoichiometric proportion of each 2 metal ions of lactoferrin molecules.One metal Ions binding bag is positioned at the N end lobule (N-lobule) of lactoferrin, and another bag is positioned at C end lobule (C-lobule).Cattle and human milk fortune The sequence of the checking of ferritin (lactoferrin precursor), lactoferrin and peptide therein may refer to Swiss-Prot (http: // au.expasy.org/cgi-bin/sprot-search-ful).Before the lactoferrin polypeptide indicated includes Lac Bovis seu Bubali transferrin Body accession number P24627, Bovine Lactoferrin, people's lactotransferrin precursor accession number P02788 and human lactoferrin.Disclosed international Patent application WO2006/054908 and WO2007/043900 reports lactoferrin polypeptide, its fragment, hydrolysate and aminoacid The preparation (including the separation from Ruzhong) of sequence and purposes, each application is merged in herein by quoting.Lactoferrin is many Peptide can be in conjunction with the metal ion of " natural " level, it is common that iron ion.Such as, Bovine Lactoferrin is natural about 10% to 20% (preferably 15%) ferrum is saturated.The Apolactoferrin that at least 1% metal ion is saturated can be used herein And lactoferrin (apolactoferrin).

Term " metal ion lactoferrin ", " lactoferrin that metal ion is saturated ", " metal ion lactoferrin sheet Section " and " lactoferrin fragment that metal ion is saturated " be intended to indicate that the lactoferrin of colony of offer metal ion binding pocket is many Peptide or the colony of fragment, wherein present in this colony, the metal ion binding pocket of at least about 25% has the metal ion of combination. Should be appreciated that described colony can comprise the polypeptide of different plant species；Such as, some molecules not coupled ion, and other molecule is every Individual combine 1 or 2 ion.Using in the case of different metal ion, some molecules can with bind metal ion, this metal from Son is selected from aluminum, bismuth, copper, chromium, cobalt, gold, ferrum, manganese, osmium, platinum, ruthenium, zinc ion or in lactoferrin metal ion binding pocket Other ion that specificity coordinates, and other molecule can be in conjunction with different ions.In some cases, described colony is permissible Comprising the polypeptide relevant with non-specific ions binding, wherein one or more ions, metal ion, is non-specific knot Close, i.e. be not combined with polypeptide in metal ion binding pocket.Can be with the ion of lactoferrin polypeptide non-specific binding Limiting examples is calcium and selenium.The change of saturation can be realized, and spectrophotometric can be used by known method Analyze and determine this saturation-for example, see disclosed international application WO2007/043900, this application herein by quote by It is incorporated to.In one embodiment, present in the colony of lactoferrin molecules at least about 1%, 5%, 10%, 15%, 20%, 25%, 30%、35%、40%、45%、50%、55%、60%、65%、70%、75%、80%、85%、90%、91%、92%、93%、94%、95%、96%、 97%, the metal ion binding pocket of 98%, 99%, 99.5%, 99.9% or 100% has the metal ion of combination, and can be arbitrarily (such as, about 5% to about 100%, about 10% to about 100%, about 15% to about 100%, about 20% to select the scope that can use between aforementioned value To about 100%, about 25% to about 100%, about 30% to about 100%, about 35% to about 100%, about 40% to about 100%, about 45% to about 100%, about 50% to about 100%, about 55% to about 100%, about 60% to about 100%, about 65% to about 100%, about 70% to about 100%, about 75% to about 100%, about 80% to about 100%, about 85% to about 100%, about 90% to about 100%, about 95% to about 100% and about 99% to About 100%).

Term " butterfat " includes mammalian lipid and lipid part, lipid hydrolysis thing and lipid part hydrolysate.At certain In a little embodiments, butterfat can be any mammal butterfat, include but not limited to cattle, sheep, goat, pig, Mus, Babalus bubalis L., Camel, yak, horse, donkey, yamma or people's butterfat, wherein butter fat is preferably to originate.Preferred milk fat is fat of dairy product, especially It it is butter fat.Preferred milk fat contains the Palmic acid of one or more, oleic acid, stearic acid or myristic acid, and they are as existence The abundantest fatty acid, it is preferable that Palmic acid, oleic acid, stearic acid and myristic acid are the abundantest fatty acids existed.Spy In other preferred embodiment, the dilutest butter or the butterfat of AMF, such as there is a) weight substantially the same with common butter fat The Palmic acid of percentage ratio (about 23% (w/w) to about 32% (w/w), normally about 28% (w/w)-see table 1.2, PF Fox and PLH McSweeney eds,Advanced Dairy Chemistry Volume2-Lipids,3rd Ed,Springer NY, NY(2006)ISBN-10:0-387-26364-0)；B) oleic acid (about 15% of percentage by weight substantially the same with common butter fat (w/w) to about 22% (w/w), normally about 17% (w/w)-see Fox and McSweeny, with the most above)；C) with common butter fat Stearic acid (about 10% (w/w) to about 15% (w/w), normally about 12% (w/w)-see Fox of substantially the same percentage by weight And McSweeny is with above)；D) (about 9% (w/w) is extremely for the myristic acid of percentage by weight substantially the same with common butter fat About 12% (w/w), normally about 11% (w/w)-see Fox and McSweeny with above)；E) above-mentioned a), b), c) or d) in Any two kinds；F) above-mentioned a), b), c) or d) in any three kinds；G) above-mentioned a), b), c) and d) in each of.Anhydrous lactitol Fat (AMF) is preferred, particularly has Palmic acid, oleic acid and the tristearin of percentage by weight substantially the same with common butter fat The AMF of acid composition, the AMF more preferably with the fatty acid composition substantially the same with common butter fat (see Fox and McSweeny, with above).Preferably butterfat part also includes dilute butter, butter, and anhydrous milkfat (AMF) is (generally by dilute butter Phase reversal or the dehydration of butter prepare), buttermilk, butter serum, β serum, from the hard breast in the one or more stages separated Fat part (includes H, SH and SSH part), and the soft butterfat part from the one or more stages separated (includes S, SS and SSS Part), the combination of hard butterfat part, the combination of soft butterfat part, hard butterfat part and the combination of soft butterfat part, glycosphingolipid fraction (include sphingomyelins part, ceramide moiety, cerebroside part or ganglioside moieties or above-mentioned the most two or more Kind combination in any), butterfat ball membrane lipid part, phospholipid moiety and complex lipid part or above-mentioned any two or more Combination in any and the hydrolysate of above-mentioned any one or more and the part of hydrolysate, arbitrarily two or more hydrolysates Combination and one or more hydrolyzable moieties and/or the combination of one or more non-hydrolytic parts.Preferably, described butterfat bag Containing at least about 20%, 30%, 40%, 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99% or the lipid of 100%, and can be arbitrarily (such as, about 60% to about 100%, about 70% to about 100%, about 80% to about 100%, about 85% to select the scope that can use between these values To about 100%, about 90% to about 100%, about 95% to about 100%, about 96% to about 100%, about 97% to about 100%, about 98% to about 100% and about 99% to about 100%, preferably from about 40% or higher than 40% to about 100%).

Term " oral administration " includes being administered orally, buccal, enteral and intragastric administration.

Term " parenteral " include but not limited to local (including any skin, epidermis or skin and mucocutaneous administration), Subcutaneous, intravenous, intraperitoneal, intramuscular adminstration.

Term " pharmaceutically acceptable carrier " is intended to indicate that and includes but not limited to excipient, diluent, auxiliary agent or a combination thereof Carrier, when the dosage of the compound or compositions that be enough to deliver effective dose useful herein is administered, described load Individuality can be administered as the component of compositions as herein described and not reduce the activity of said composition and do not have by body Toxicity.Preparation can oral administration, intranasal administration or parenteral (include topical, intramuscular adminstration, intraperitoneal to Medicine, subcutaneous administration and intravenous administration).

" individual " is animal, preferred mammal, more preferably mammal companion animal (companion animal) or People.Preferably companion animal includes cat, Canis familiaris L. and horse.In one embodiment, artificial adult, children or infants or immunity are subject to The adult of damage, children or infants.

Term " is treated " or its derivative should be interpreted its most possible connotation.This term is understood not to secretly Show and individuality is treated until returning to one's perfect health.Therefore, broadly include paresthesia epilepsy or particular state serious " is treated " The improvement of property and/or prevention.

2. butterfat separates with butterfat

Fox and McSweeney (2006) discusses butterfat comprehensively, and this list of references is merged in herein by quoting. In addition to lipid, butterfat also includes vitamin, sterol and less component.See the chapter 1 of Fox and McSweeney Composition and Structure of Bovine Milk Lipids (compositions of Lac Bovis seu Bubali lipid and structure), uses In describing naturally occurring butter fat.Dairy Processing Handbook (Dairy Processing handbook), 1995 and Illingworth, 2002, and Rombaut et al., 2006 (b) discusses the separation of butterfat, and these lists of references all lead to herein Cross to quote and be merged in.Fox and McSweeney (2006) discusses the seasonal variations of butterfat.

The example of butterfat part useful in the present invention include dilute butter (fat of normally about 20% to about 40% weight ratio, The fat of preferably from about 40% weight ratio), butter, butter, anhydrous milkfat (AMF) is (generally by the phase reversal of dilute butter or butter Dehydration preparation), buttermilk, butter serum, β serum, hard butterfat part, soft butterfat part, glycosphingolipid fraction, butterfat ball film part, phosphorus Fat part and complex lipid (each molecule produces 3 kinds or the lipid of further types of hydrolysate) part and combinations of the above and upper The hydrolysate stated.

Such as Bylund, 1995, Rombaut et al, 2005；Rombaut et al,2006(a)；Rombaut et Al, 2006 (b) and disclosed international application WO2006/041316 discuss buttermilk, butter serum and β serum, all these ginsengs Examine document to be merged in herein by quoting.Buttermilk is used to describe employing cream preparation method and obtains from conventional cream produces The term of waterborne liquid phase, this cream preparation method can be batch (churning (churn)) method or (Fritz) side continuously Method.Buttermilk is also used to describe by aqueous produced by the dilute butter concentration step in the conventional method preparing AMF from dilute butter The term of by-product.This conventional method relates to the concentration of dilute butter and transfers preparation oil the most on the contrary, is concentrated further by this oil And grind (polish) and prepare AMF.Finally, buttermilk is also used to two serums (two-serum) method of description AMF production The term of the combination of secondary degreasing thing (secondary skim) and β serum by-product, for example, see Bylund (Ed., 1995) With disclosed international application WO2006/041316 (seeing Fig. 2), these lists of references describe in detail this method.At this In two plasma method, dilute butter concentration step the by-product obtained is separated further and produces secondary degreasing thing, and will be from The by-product that oil concentration step obtains separates further prepares β-serum.In the first two example, occur in any phase reversal Before prepare buttermilk.In the 3rd example, buttermilk is the β serum of preparation after the secondary degreasing thing of preparation and phase reversal before phase reversal Combination.In these methods, generally by be centrifuged realize concentrate and grind.Generally realize phase reversal by homogenization. Should be appreciated that the source of these dairy lipid parts can be breast or colostrum or a combination thereof.

Dilute butter that raw material useful in separation includes obtaining from breast or colostrum or a combination thereof, AMF, buttermilk, butter breast Slurry or β serum.

The multiple stage separation (multistage fractionation) carrying out butterfat can be crystallized by difference.By butterfat Part be heated to set temperature, and the part of fractional crystallization or solid (" stearic "-hard portion) part with liquid (" olein "- Soft part) part.Multiple stage separation means separating again in the subsequent step of the previously product of separating step.Can be by by mother Soft it be partially separated into soft hard thin part (sub-fraction) and prepare the soft part of continuous print.

Other partition method include phase reversal, ester exchange, glycerolysis, solvent separate (such as individually or order use ethanol, Water or acetone), supercritical separates (for example, see Astaire, et al, 2003), near critical separates (for example, see WO2004/ 066744), distillation, centrifugation, suspension crystallization, drying crystalline, the separation of use modifying agent (such as soap or emulsifying agent), super Filter, microfiltration and any method separated for lipid known in the art and the combination of these methods, all these methods are equal It is known in the art.

In one embodiment, separation method selected from individually or order utilize ethanol, water or acetone to dilute butter, AMF, The solvent that buttermilk, butter serum or β serum are carried out separates.

Present in the present composition, lipid can be by completely or partially modified, the most natural, chemical, enzymatic, Or by arbitrarily other method known in the art, these lipids include, such as, glycosylation, sialylated, esterification, phosphorylation Or the lipid of hydrolysis.Lipid hydrolysis thing can utilize known technology to prepare, and this known technology includes but not limited to sour water Solution, basic hydrolysis, such as Fox and McSweeney ((2006), Chapter15by HC Deeth and CH Fitz-Gerald) The enzyme hydrolysis utilizing lipase of described enzyme hydrolysis and fermentable.A kind of method of basic hydrolysis includes adding 1%KOH (being dissolved in ethanol), and heat 10 minutes.The material of hydrolysis can neutralize with acetic acid or hydrochloric acid.

Butterfat ball membrane material can be according to Kanno&Dong-Hyun, and the acidization tool of 1990 separates, and can pass through Such as Kanno et al, butterfat ball membrane material is further separated into lipid and protein by the method adding methanol described in 1975 Part.According to Purthi et al, the step of 1970, separating phospholipids portion can be come by utilizing acetone extract lipid mixture Point.By the pentane selective extraction to non-polar lipid, lipid residue can be enriched in butterfat ball membrane lipid further.

Disclosed international patent application WO2006/041316, WO2007/123424 and WO2007/123425 also illustrate Being partially separated method for preparing butterfat useful herein, each application is totally integrating herein by quoting.

Particularly preferred butterfat useful herein be partly comprised in those the butterfat parts described in Examples below and Those the butterfat parts summed up in the following table.These parts can be emulsion or dry, it is also possible to is powder, and this part is appointed Selection of land is added together with the component containing the fluidizer of such as lactose and is improved mobility.

Table 6-butterfat part

< 0.01=trace

Table 7-phospholipid and ganglioside moieties

	Part
													7	8	9	10	11	12	13	14	15	16	17
Composition (%w/w)	β serum						PC500^TM	PC700^TM		G500^TM	G600^T ^M
												Protein	30.2	49.7	60.2	<0.01	<0.01	12.4	0.0	0.0	ND	< 2%	10.2
MFGM	7.5	11.9	14.4	0.2	ND	ND	0.0	0.0	ND	ND	ND
												Fat	20.6	35.6	23.1	94.2	86.8	90.2	87.0	84.4	84.6	35.5	27.9
Phospholipid	9.7	14.9	16.0	31.0	65.7	66.8	24.7	60.2	27.6	17.6	15.1
												PC	2.5	3.8	4.9	8.1	16.8	15.0	8.0	19.2	3.2	3.1	2.0
PI	0.8	1.1	1.5	2.8	5.8	6.0	0.7	2.0	6.0	2.8	2.9
												PS	1.1	1.6	2.1	4.3	8.7	7.6	1.0	2.4	7.3	3.5	4.0
PE	2.8	4.3	5.4	11.3	23.6	21.8	7.7	17.0	6.4	4.9	4.4
												SM	2.4	3.6	4.5	7.5	16.5	13.6	6.9	16.7	3.5	2.8	1.6
Ganglioside	0.4	0.7	1.0	1.2	2.0	2.0	0.0	0.0	4.5	1.3	2.0
												GD3	0.4	0.6	0.9	1.1	1.8	1.8	0.0	0.0	4.0	0.6	1.8
Lactose	ND	7.8	11.7	2.6	6.4	4.0	4.1	6.2	8.3	54.9	58.0
												Ash	ND	5.2	5.9	3.1	12.1	9.1	13.3	7.4	7.0	5.0	8.3
Moisture	1.9	2.7	2.9	2.6	4.6	2.3	2.2	2.0	3.7	3.2	2.8

ND=is not detected by；< 0.01=trace

3. the useful compositions of invention

Compositions useful herein can be formulated as food, beverage, food additive, beverage additive, nutrition benefit Fill agent, nutriment, medicated food, enteral or parenteral and feed product, generation meal, cosmeceutical or medicine (pharmaceutical).Those skilled in the art can prepare suitable preparation according to the teaching of technical ability and this specification.

In one embodiment, compositions useful herein includes any edible consumption that can be loaded with lipid Product.The suitably example of edible consumer goods includes powder, liquid, the confection system including chocolate, gel, ice cream Product, the fruit product of reduction, snack bar (snack bars), food bars, muesli bar, tablespread, sauce, dips in Liquid, the milk product including Yoghurt and cheese, include based on the beverage including milk and beverage based on non-dairy (such as Milk beverage and boruga), milk powder, include based on the sports supplement including milk and sports supplement based on non-dairy, Such as albumen dispenses the food additive of microgranule, include the nutritional supplementation goods supplemented day including tablet, ablactational food and Yoghourt And the such as infant formula that powder or liquid form exist, bigger infant formula or the milk replacer of growth milk replacer.? In this embodiment, preferred composition useful herein can be powder or the infant formula of liquid form, bigger baby Youngster's milk replacer or growth milk replacer.Suitable Halth-care composition useful in the present invention can be provided in a comparable fashion.

Powder or the such as infant formula of liquid form, the reality of the milk replacer of bigger infant formula or growth milk replacer Example includes following example.One example bag of infant formula useful herein, bigger infant formula or growth milk replacer Containing (w/w)

The lactose of (a) 30%-60%

The vegetable oil of (b) 15%-35%

The skimmed milk powder of (c) 0%-40%

The lactalbumin of (d) 0%-40%, such as WPC or WPI, the WPC (WPC80) of preferably 80%

The reagent useful herein of (e) 1%-50%.

Infant formula useful herein, another example of bigger infant formula or growth milk replacer comprises (w/w)

The lactose of (a) 40%-60%

The vegetable oil of (b) 20%-30%

The skimmed milk powder of (c) 10%-15%

The lactalbumin of (d) 6%-8%, preferably WPC80

The reagent useful herein of (e) 1%-10%.

The lactose of (a) 40%-60%

The vegetable oil of (b) 20%-30%

The skimmed milk powder of (c) 10%-15%

The lactalbumin of (d) 6%-8%, preferably WPC80

The reagent useful herein of (e) 1%-5%.

The lactose of (a) 40%-60%

The vegetable oil of (b) 20%-30%

The skimmed milk powder of (c) 10%-15%

The lactalbumin of (d) 6%-8%, preferably WPC80

The reagent useful herein of (e) 2%-5%.

Infant formula useful in the present invention, another example of bigger infant formula or growth milk replacer comprises (w/ w)

The lactose of (a) 30%-60%

The vegetable oil of (b) 15%-35%

The skimmed milk powder of (c) 0%-40%

The lactalbumin of (d) 0%-40%, preferably WPC80

The reagent useful herein of (e) 1%-50%, such as β fermented milk powder or its part, or β fermented milk powder and its portion Point, as from polar lipid rich in or the part that obtains of β serum that lacks in neutral lipid.

The lactose of (a) 40%-60%

The vegetable oil of (b) 20%-30%

The skimmed milk powder of (c) 10%-15%

The lactalbumin of (d) 6%-8%, preferably WPC80

The reagent useful herein of (e) 1%-5%, such as β fermented milk powder or its part, or β fermented milk powder and its portion Point, as from polar lipid rich in or the part that obtains of β serum that lacks in neutral lipid.

These any infant formulas can also comprise the one of 0.1%w/w to 4%w/w, preferably 2%w/w to 4%w/w/ Or multivitamin premix (premix), mineral premix, phosphatidylcholine, one or more antioxidants, one Kind or plurality of stable agent or one or more nucleotide or above-mentioned two or more combination any.Some embodiment party In case, these infant formulas can be prepared to provide the heat of 2700kJ/L to 3000kJ/L.

In selectable embodiment, compositions useful herein can be prepared and allow the way by any selection Individuality is administered by footpath, and this approach includes but not limited to administered orally or parenterally (include topical, subcutaneous administration, intramuscular It is administered and intravenous administration).

Therefore, it can join with suitable pharmaceutically acceptable carrier (including excipient, diluent, auxiliary agent and combinations thereof) The useful pharmaceutical composition of the present invention processed, and select this carrier according to the expectation approach being administered with standard pharmaceutical practice. Such as, the useful compositions of the present invention can carry out oral administration with the form of powder, liquid, tablet or capsule, or Topical is carried out with the form of ointment, emulsifiable paste or washing liquid.Suitably preparation can be containing required additive (additional Agent), including emulsifying agent, antioxidant, flavoring agent or coloring agent, and this suitable preparation can be made to be applicable to rapid release, delay Release (delayed release), modified release (modified release), slow release (sustained release), pulse are released Put or controlled release.

Capsule can contain the pharmaceutically acceptable material of any standard of such as gel or cellulose.Can be according to routine Step, by preparing tablet by the mixture compacting of active component with solid carrier and lubricant.The example bag of solid carrier Include starch and sugar bentonite.Active component also be able to the binding agent containing such as lactose or mannitol, conventional filler and The duricrust tablet of tablet agent or the form of capsule are administered.Pharmaceutical composition also be able to by parenteral route carry out to Medicine.The example of parenteral dosage forms includes aqueous solution, isotonic saline solution or 5% glucose solution containing activating agent, or known to other Pharmaceutically acceptable excipient.Cyclodextrin or other solubilizing agent well known by persons skilled in the art can act as drug excipient For delivering therapeutic agent.

The effect of the useful compositions of the present invention can be estimated in vitro and in vivo.For example, see following instance. In brief, it is possible to described compositions suppresses the ability of external rotavirus infection test.For In vivo study, energy Enough feed or inject described compositions to animal (such as mice), then evaluate the effect that virus is infected by said composition.Based on Result of study, it is possible to determine suitable dosage range and route of administration.

Compositions useful herein can be used alone or use with one or more other therapeutic combination.Should Therapeutic agent can be food, beverage, food additive, beverage additive, food component, beverage ingredient, supplementary, nutrition Product, medicated food, health product, medicine (medicament) or medicine (pharmaceutical).Described therapeutic agent is the most effective Ground weakens the symptom of one or more rotavirus infections.

When using with other therapeutic combination, compositions useful herein can be administered simultaneously or sequentially and other is controlled Treat agent.It is administered simultaneously administration or the different dosage form administration substantially simultaneously of the single dosage form including comprising whole component.Sequentially It is administered and includes the administration according to different schemes, be preferably to provide the cycle of compositions useful herein and other therapeutic agent There is overlap.

The suitable agent of (co-administered) can be administered altogether with compositions useful herein and include antiviral Agent, theaflavin, protease inhibitor, Yolk immunoglobulin, the sulphation sialic acid lipid NMSO of synthesis₃, human milk adhesion egg (glycoprotein of butterfat ball film), MUC1 mucin, cattle macromole whey fraction and combinations of the above in vain, and other is suitable Reagent known in the art.

In one embodiment, compositions useful herein include breast component or with breast component simultaneously or sequentially to Medicine, this breast component such as lactalbumin, whey fraction (include acidity or alkalescence whey fraction or a combination thereof), sugar huge Peptide, lactoferrin, ferrum-lactoferrin, functional lactoferrin variant, functional lactoferrin fragment, vitamin D or calcium or on The combination stated.The useful compositions containing breast component includes such as, food, beverage, food additive, beverage additive, battalion Support supplement, nutriment, medicated food and health product.The newborn part rich in these components can also be used.In international monopoly Shen Please describe useful lactoferrin, fragment and compositions in WO03/082921 and WO2007/043900, the two application exists It is integrally incorporated herein here by quoting.

Should be appreciated that and above listed other therapeutic agent can also be used in the method for the invention (based on food Reagent and medicament), wherein this therapeutic agent is administered respectively, simultaneously or sequentially together with compositions useful herein.

Should be appreciated that and depend on following variable condition, the dosage of the compositions of administration, dosage period and conventional administration side Formula is different between patient: as individual symptom seriousness, want sanatory type, select the pattern, the individuality that are administered Age, sex and/or general health.But, as general example, inventors believe that every day, every kg body weight was administered about The compositions useful herein of 1mg to about 1000mg, preferably every kg every day about 50mg is to about 500mg, or 150mg/kg/ days To about 410mg/kg/ days, or about 110mg/kg/ days to about 310mg/kg/ days.In one embodiment, inventors believe that Every kg body weight is administered the pharmaceutical composition useful herein of about 0.05mg to about 250mg.

Should be appreciated that and be administered the administration that can include single daily dosage, or suitable the most discontinuous fractionated dose It is administered.

By with reference to following example, various aspects of the invention being described in a non-limiting manner.

Embodiment

Sample analysis

Protein level is multiplied by 6.38 by total nitrogen and determines.Phospholipid level passes through³¹P NMR determines.Ganglioside Lipid level determines by the following method.The powder of three parts of about 0.1g is weighed in the kimax test tube of 16ml and records weight.Add Add the methanol of 6ml and by eddy current mixing 1min.Solution is hatched 10min at 50 DEG C, then adds 6ml water and pass through eddy current Mixing.Solution stands at 4 DEG C 2hr settle, sample takes out and passes through the filter of 0.45 μm.This is analyzed by HPLC Sample.Use and protect (security guard) (Phenomenex with NH2^TMIn KJO-4282 column sleeve (holder) Phenomenex^TMAJO-4302) Cosmosil^TM5NH2-MS waters post (Nacalai Tesque Inc, USA).Point The every day of analysis all changes guard column (guard cartrige).By in sample feeding to post, and use the solvent orange 2 A (second of 90% The 5mM phosphate buffer pH5.6 of nitrile, the water of 5% and 5%) and solvent B (the 200mM phosphoric acid of the acetonitrile of 50%, the water of 45% and 5% Salt buffer pH5.6), carry out eluting with the flow velocity of 2ml/min.Use following gradient: the A of 100% keeps 3.5min, then In 26.5min by 100% the A of A to 55%, then in 1min by 55% the A of A to 100%, then the A of 100% keeps 5min (Wagener et al.(1996),Journal of Lipid Research37,1823-1829).Use buttermilk GD3 (Matreya#1504) external standard curve of 0 μ g to 2 μ g GD3 is generated.Eluting is monitored under 203nm.

The preparation of lipid and other dairy material

Butterfat part (including β serum), lactoferrin, Sialyl Oligolac^TMBreast extract and butterfat ball film (MFGM) Material is provided by Fonterra Co-operative Group Limited (New Zealand).Sialyl Oligolac^TMBreast extracts Thing is the spray-dried powders being derived from colostrum, and this breast extract contains high level genuine milk oligosaccharide, mineral and free sum Sialic acid (protein ((former state (as is)) 8.7%, lactose 61.7%, moisture 3.9%, the fat being combined with carbohydrate 0.08%, ash 18.9%, free sialic acid 2.5mg/g, the sialic acid 9.3mg/g of combination).Sialyl Oligolac^TMContain 3 ' sialyl lactoses and two sialyl lactoses, they are respectively derived from the free form of the polysaccharide of Ganglioside GM3 and GD3. MFGM and MFGM protein part in table 10 is prepared by New Zealand milk fat according to known method.

AMF and AMF part

AMF, AMF huttriall provided by Fonterra Co-operative Group Limited is provided Divide (SH and SSH) and the soft part of AMF (SSS).

The butterfat of high CLA contains the CLA of 5.4%, and according to known method fish oil and sunflower oil feeding cow then Prepared anhydrous milkfat by the breast produced to prepare.Disclosed international pct application WO2005/107736 describes rich in CLA The common compositions of butterfat, this application is merged in by quoting at this.

Phospholipid moiety

Below part 7 to 11 that is described and that used in the examples below is special according to the disclosed world in table 7 Profit application method described in WO2006/041316 prepares (seeing embodiment 3 to 6).Part 12 is by the phospholipid moiety in table 7 Prepared by the supercritical carbon dioxide extraction of 10.Part 15 is extracted by the ethanol of β fermented milk powder to be prepared.

Extracted by the ethanol of β fermented milk powder and prepare Phospholipid Concentrate PC500^TMPhospholipid moiety (from Fonterra Co-operative Group Limited, New Zealand).β serum is the liquid produced in prepared by AMF Phase.PC500^TMPhospholipid moiety is the newborn phospholipid concentrate being spray-dried, it is common consist of 77% to 95% TL, about 50% Neutral lipid and the polar lipid of about 30%；And common iipidomic become 1.5% to 5% Phosphatidylserine, 12% to The phosphatidylcholine of 18%, the PHOSPHATIDYL ETHANOLAMINE of 6% to 9% and the sphingomyelins of 6.7% to 9%；And common fatty acid forms For butanoic acid (4:0) 1.8%, capric acid (10:0) 0.3%, lauric acid (12:0) 0.5%, myristic acid (14:0) 7.4%, myristoleic acid (14:1) 14.1%, pentadecanoic acid (15:0) 1.0%, Palmic acid (16:0) 26.0%, palmitoleic acid (16:1) 1.7%, heptadecanoic acid (17:0) 0.6%, heptadecenoic acid (17:1) 0.3%, stearic acid (18:0) 11.9%, oleic acid (18:1) 39.0%, linoleic acid (18: 2) 5.0%, linolenic acid (18:3) 2.0%, arachidic acid (20:0) 0.3% and cholesterol 0.8%.

Pass through PC500^TMThe acetone extract of phospholipid moiety prepares Phospholipid Concentrate PC600^TMPhosphorus Fat part (from Fonterra Co-operative Group Limited, New Zealand).PC600^TMPhospholipid moiety is freezing dry Dry newborn phospholipid concentrate, polar lipid that it is common consists of 75%, the neutral lipid of 8.0%, ash less than 12% and little In the moisture of 4%；Common iipidomic become 3% to 4% Phosphatidylserine, phosphatidylcholine more than 36%, more than 9% PHOSPHATIDYL ETHANOLAMINE and the sphingomyelins more than 18%；And common fatty acid consists of myristic acid (14:0) 6.6%, Palmic acid (16:0) 27.1%, palmitoleic acid (16:1) 1.3%, heptadecanoic acid (17:0) 2.3%, stearic acid (18:0) 14%, oleic acid (18:1) 38.2%, linoleic acid (18:2) 6.5%, linolenic acid (18:3) 2%, cholesterol 0.1% and other 2%.

Pass through PC500^TMThe aqueous extraction (degumming) of phospholipid moiety prepares Phospholipid Concentrate PC700^TMPhospholipid moiety (from Fonterra Co-operative Group Limited, New Zealand).PC700^TMPhospholipid portion It is divided into lyophilization breast phospholipid concentrate, its common lipid, the ash of 10%, the lactose of 2% and water of 2.5% consisting of 85% Point；Common iipidomic becomes Phosphatidylserine 3%, phosphatidylcholine 31%, PHOSPHATIDYL ETHANOLAMINE 8.7% and sphingomyelins 16.5%；And common fatty acid consist of myristic acid (14:0) 5.4%, Palmic acid (16:0) 20.9%, palmitoleic acid (16: 1) 1.3%, heptadecanoic acid (17:0) 0.5%, stearic acid (18:0) 10.5%, oleic acid (18:1) 30.5%, linoleic acid (18:2) 4.3%, Linolenic acid (18:3) 1.8% and arachidonic acid 0.5%.

Ganglioside moieties

Below part 7 to 11 that is described and that used in the examples below is special according to the disclosed world in table 7 Profit application method described in WO2006/041316 prepares (seeing embodiment 3 to 6).Part 12 is by phospholipid moiety 10 in table 7 Supercritical carbon dioxide extraction prepare.Part 15 is extracted by the ethanol of β fermented milk powder to be prepared.

Extracted by the ethanol of β fermented milk powder and prepare G500^TMAnd G600^TMGanglioside moieties is (from Fonterra Co-operative Group Limited, New Zealand).β serum is the liquid phase produced in AMF preparation process.

G500^TMGanglioside moieties is the newborn ganglioside concentrate being spray-dried, and with the addition of lactose With WPC (Lactalbumin concentrate) to improve powder flowbility.G500^TMThe common of ganglioside moieties consists of lipid 34.0%, moisture 3.2%, ash 5.0% and lactose 56.0%；Common iipidomic becomes Ganglioside, GD3 0.6% and neuroganglion Glycosides fat GM30.5%；And common fatty acid consists of myristic acid (14:0) 5.6%, Palmic acid (16:0) 18.4%, Petiolus Trachycarpi oil Acid (16:1) 1.2%, heptadecanoic acid (17:0) 0.5%, stearic acid (18:0) 14.9%, oleic acid (18:1) 31.0%, linoleic acid (18: 2) 3.8%, linolenic acid (18:3) 1.5% and arachidonic acid (20:4) 0.5%.

Ganglioside G600^TMGanglioside moieties is the newborn ganglioside concentrate being spray-dried, Qi Zhongyi Through with the addition of lactose to improve powder flowbility.G600^TMThe common of ganglioside moieties consists of lipid 30.0%, moisture 3.5%, ash 8.3% and lactose 58.0%；Common iipidomic become Ganglioside, GD3 1.4%, Ganglioside GM3 0.3%, Phosphatidylserine 4.5%, phosphatidylcholine 5.1%, PHOSPHATIDYL ETHANOLAMINE 2.0% and sphingomyelins 1.7%；And common fatty acid Consist of myristic acid (14:0) 4.7%, Palmic acid (16:0) 16.4%, palmitoleic acid (16:1) 1.2%, heptadecanoic acid (17:0) 0.5%, stearic acid (18:0) 17.0%, oleic acid (18:1) 33.4%, linoleic acid (18:2) 4.2%, linolenic acid (18:3) 1.4% and flower Raw tetraenoic acid (20:4) 0.6%.

Lipid hydrolysis thing

Realize by adding the potassium hydroxide (ethanol solution of 1.5%) of 800 μ l in sample prepared by 200mg lipid Partly-hydrolysed.The solution of gained is mixed 10 minutes, and to be neutralized to pH value with hydrochloric acid (10%) be 7.Then by this solution at nitrogen Undershoot does (flush dry).

Cell cultivation, virus breeding and mensuration material

All of cell culture material is purchased from Invitrogen.Rotavirus strain Wa (people) is University of Auckland The John Taylor of (Auckland University) gives.HT29 cell is purchased from ATCC (HTB-38).Single sialic acid god Warp knuckle glycosides fat GM3cat#1503 and two ganglioside sialic acid GD3cat#l504 purchased from Matreya (Pleasant Gap, PA,USA)。

Rotavirus is bred

Containing l μ g/ml tryptic Dulbecco MEM (Dulbecco's minimal Essential medium) in the presence of (DMEM), it is used for HT29 cell line breeding Human reoviruslike agent strain Wa (neuraminic acid Enzyme resistance), the hyclone of this culture media supplemented 10% and penicillin/streptomycin (l00 μ g/ml/l00 unit/ml).Pass through Rotavirus is gathered in the crops in twice freeze thawing, is centrifuged to remove cell debris by this virus and is stored in-80 DEG C under 750g.To colyliform Virus is measured, and finds that it contains 1 × 106 plaque forming unit (pfu)/ml.

Rotavirus infection measures

It is based on measuring (Scott et al1979 disclosed in many that infection used measures;Smith et al1979; Guarino et al1996;Superti et al2001).DMEM (inoculating in 96 orifice plates) will be grown in 3 × 105/ml In fusion HT29 cell wash twice in aseptic PBS.In plate, carry out each wanting examination in the DMEM of 50 μ l volumes The double dilution of product (initial concentration 5mg/ml).Except the comparison of only cell, in all of hole, add virus (104pfu/ hole), then at 37 DEG C, is hatching plate two hours in the CO2 of 5%.Other comparison includes virus refinement Born of the same parents, only lipid, pure GM3 and pure GD3.After hatching two hours, adding trypsin to all of hole, 2 μ g/ml are contained in this hole The step for of concentration viral, VP4 is cut into polypeptide VP8 and VP5, and it is required to be that virion invades intracellular institute 's.Plate is hatched seven days at 37 DEG C and in the CO2 of 5%, and every day checks the cytopathogenic effect in the most virulent control wells Effect.Remove culture medium, plate is washed in aseptic PBS, air-dry and fix one minute with methanol.Plate is air-dried, then with 100 1% crystal violet (351884W, BDH, England) in μ l/ hole dyes five minutes.By plate sterilized water wash four times unnecessary to remove Stain.Add the acetic acid of every hole 100 μ l to dissolve stain, and at Biorad ELISA microwell plate detector (plate Reader), in, under the wavelength of 595nm, absorbance is read.In the case of minimum of three is independent, measures each sample, and calculates The percentage rate of the most infected cell.

Statistics

Non-matching Student t inspection (for Macintosh, use InStat) is utilized to carry out statistical analysis, Thus under the minimum dilution of product, the effect stemming from the lipid products of Lac Bovis seu Bubali is compared with the most virulent comparison.

Embodiment 1-dairy lipid suppresses external rotavirus infection

The ability of the rotavirus infection of the prevention cell of 16 kinds of lipid test materials of examination.Lipid test material or contrast Material is nontoxic to HT29 cell.Ganglioside, GD3 and GM3 all show activity (table 9) in concentration range.16 Plant in lipid test material, have the activity (table 10) that 14 kinds of viruses showing prevention cell in concentration range infect.

Table 8: in the presence of GD3 and GM3 of various concentration, not by the percentage rate of the HT29 cell of rotavirus infection

*, compared with the most virulent comparison, p is < notable when 0.01；* p is < notable when 0.005；* * p is < notable when 0.001；

The sample not having p value is the most different from the most virulent comparison.ND=undetermined.

Table 9: in the presence of the various Lac Bovis seu Bubali lipid parts of various concentration, not by the HT29 cell of rotavirus infection Percentage rate

The sample not having p value is the most different from the most virulent comparison.

When p is less than 0.001, concentration is that five kinds of test materials of 0.3125mg/ml substantially reduce infection rate (table 10).These Test material is the butterfat rich in CLA, β serum, PC700^TMPhospholipid moiety and ganglioside moieties.When p is less than 0.005, dense Four kinds of test materials that degree is 0.3125mg/ml substantially reduce infection rate.These test materials are AMF, soft butterfat part , and PC500 (SSS)^TMAnd PC600^TMPhospholipid moiety.When P is less than 0.01, concentration is three kinds of test materials of 0.3125mg/ml Substantially reduce infection rate.These test materials are other SH and SSH butterfat part, and the ganglioside moieties of hydrolysis.Surplus Under product and virus control the most different.As concentration as little as 31.25 μ g/ml, the purification of samples of GM3 and GD3 is protected Protect cell and exempt from (respectively 43+/-10% and 40+/-3% that is infected by the virus；p<0.005).On ganglioside-enriched basic, At minimum G600^TMUnder concentration, G600^TMMore effective than pure GD3 10 times of part.

Embodiment 2-dairy lipid can treat or prevent the diarrhoea caused by rotavirus infection

Young rat (baby rat) animal model infected for Human reoviruslike agent can be used in determining the internal effect of product Power (for example, with reference to Ciarlet et al2006).

With the volume of 100 μ l, by the way of delivering entrance cavity, four kinds of different lipids that concentration is 3g/kg body weight are surveyed Examination material is fed for often organizing five the biggest rat sons of ten.Other feedings all are both from lactescent female rat (mother rat).At first day and second day, be fed for for twice rat son 100 μ l dosage Human reoviruslike agent strain Wa (morning and Evening).Negative control rat is injected (inoculate) 100 μ l phosphate buffered saline(PBS) (PBS), but need not virus carry out Infect.Positive control rat is injected 100 μ l PBS, infects by virus subsequently.Test after injection rotavirus Carry out 10 days.This experiment repeats.

In order to measure infection rate, rat is weighed every day.Single fecal specimens is collected in preweighted vessel, and The determination once suffered from diarrhoea every day.According to stool colour, denseness and amount, every day carries out the marking of following 1 to 4 to diarrhoea.

1. normal fecal stools-normal color (brown) and denseness.

2. the color (green or yellow green) of mild diarrhea-exception but normal denseness.

3. mild diarrhea-normal color (brown) but watery denseness.

4. the color of severe diarrhea-exception and watery denseness.

Faecal samples is processed into 10% solution in cold (4 DEG C) PBS, and this solution contains penicillin (200U/ml), chain Mycin (200 μ l/ml) and gentamycin (2mg/ml), and repeat the decile of 10 μ l as described above to survey in cell is cultivated Fixed with the level determining infective rotavirus.In measuring in vitro, these levels represent the percentage rate of the most infected cell: The most infected cell %=(OD of test sample) * 100/ (OD of negative control), the optical density of solution during wherein OD is hole.

Table 11: the seriousness of the rat diarrhoea of the butterfat of feeding height CLA

Table 12: feeding G600^TMThe seriousness of the rat diarrhoea of butterfat

Table 13: the seriousness of the rat diarrhoea of feeding β serum part

Faecal samples is measured to determine the percentage rate of the most infected cell during rotavirus measures in vitro.For feeding Eat the rat (Figure 1A) of the butterfat of high CLA, process with the difference between infected comparison first day (P < 0.001), the 3rd My god (P < 0.025), the 7th day (P < 0.05) and the 8th day (P < 0.025) be significant.For feeding G600^TMThe rat of part (Figure 1B) difference between infected comparison, is processed at the 3rd day (P < 0.001), the 4th day (P < 0.001), the 6th day (P =0.001), the 7th day (P < 0.001) and the 8th day (P < 0.001) is significant.

Commercial Application

The present invention has practicality in treatment or prevention rotavirus infection.Described compositions can be used as food Product, beverage, food additive, beverage additive, supplementary, nutriment, medicated food, health product, medicine Or medicine (pharmaceutical) (medicament).

It will be appreciated by those skilled in the art that, only provide foregoing description, and the present invention by exemplary illustration Do not limited by these exemplary illustrations.

List of references

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Claims

1. preparing, selected from following reagent, the purposes being used for treating or preventing in the compositions of individual rotavirus infection:

(a). the isomer of one or more conjugated linoleic acids (CLA), or the isomer of the CLA of one or more esterified form, Vaccenic acid or combinations of the above, wherein the CLA of esterified form includes the CLA being combined with glyceride or phospholipid, or

(b). the butterfat of high CLA, or

(c). the butterfat part of one or more high CLA, or

(d). the hydrolysate of the butterfat of high CLA, or

(e). the hydrolysate of the butterfat part of one or more high CLA, or

(f). combinations of the above,

The butterfat of wherein said high CLA comprises the CLA of at least 2% weight ratio.

2. purposes as claimed in claim 1, it also includes selected from the second following reagent:

(i). butter fat,

(ii). one or more are rich in the part of the butter fat of phospholipid,

(iii). one or more are rich in the part of the butter fat of ganglioside,

(iv). one or more hydrolysates of any one or more in (i) to (iii), and

(v). arbitrarily two or more combination in (i) to (iv).

3. purposes as claimed in claim 1, wherein said rotavirus is Human reoviruslike agent.

4. purposes as claimed in claim 1, wherein said rotavirus is the Human reoviruslike agent of neuraminidase resistance.

5. purposes as claimed in claim 1, wherein said individuality is people.

6. purposes as claimed in claim 1, wherein said individuality is the child of immunocompromised host.

7. purposes as claimed in claim 1, wherein said individuality is the baby of immunocompromised host.

8. purposes as claimed in claim 1, wherein said individuality is the adult of the adult more than 55 years old or immunocompromised host.

9. purposes as claimed in claim 1, for treating or prevent the rotavirus infection of diarrhea inducing.

10. purposes as claimed in claim 1, the diarrhoea caused by rotavirus infection for treatment or prevention.

11. purposes as claimed in claim 1, wherein said butterfat comprises the lipid of 5% to 100%.

12. purposes as claimed in claim 1, wherein said butterfat comprises the lipid of 40% to 100%.

13. purposes as claimed in claim 2, wherein said butter fat is anhydrous butter fat (AMF).

14. purposes as claimed in claim 2, wherein said butter fat is selected from following AMF part: one or more are the most newborn Fat part or one or more soft butterfat parts.

15. purposes as claimed in claim 2, the wherein said part rich in phospholipid or the part rich in ganglioside comprise

The lipid of (a) 5%w/w to 95%w/w and the protein of 0%w/w to 75%w/w, or

The lipid of (b) 15%w/w to 95%w/w and the protein of 0%w/w to 75%w/w, or

The lipid of (c) 5%w/w to 95%w/w, the protein of 0%w/w to 75%w/w, the phospholipid of 5%w/w to 85%w/w and The ganglioside of 0%w/w to 5%w/w, or

The lipid of (d) 15%w/w to 95%w/w, the protein of 0%w/w to 65%w/w, the phospholipid of 5%w/w to 70%w/w and The ganglioside of 0%w/w to 2.5%w/w.

16. purposes as claimed in claim 2, the wherein said part rich in phospholipid or the part rich in ganglioside comprise

The protein of (a) 25%w/w to 35%w/w, the lipid of 12%w/w to 25%w/w, the phospholipid of 5%w/w to 15%w/w, The MFGM albumen of 5%w/w to 15%w/w and the ganglioside of 0.2%w/w to 0.9%w/w, or

The protein of (b) 40%w/w to 60%w/w, the lipid of 25%w/w to 45%w/w, the phosphorus of 10%w/w to 25%w/w Fat, the MFGM albumen of 5%w/w to 20%w/w and the ganglioside of 0.5%w/w to 2.0%w/w, or

The protein of (c) 50%w/w to 70%w/w, the lipid of 12%w/w to 32%w/w, the phospholipid of 5%w/w to 25%w/w, The phosphatidylcholine of 2%w/w to 8%w/w, the PHOSPHATIDYL ETHANOLAMINE of 2%w/w to 10%w/w, the sheath phosphorus of 2%w/w to 8%w/w Fat and the Phosphatidylserine of 1%w/w to 3%w/w, the MFGM albumen of 10%w/w to 20%w/w and 0.5%w/w to 2.5% The ganglioside of w/w, or

The protein of (d) 0%w/w to 10%w/w, the lipid of 85%w/w to 97%w/w, the phospholipid of 25% to 35%w/w, 5% The phosphatidylcholine of w/w to 10%w/w, the PHOSPHATIDYL ETHANOLAMINE of 7%w/w to 13%w/w, the sheath phosphorus of 4%w/w to 9%w/w Fat, the Phosphatidylserine of 2%w/w to 5%w/w, the phosphatidylinositols of 1%w/w to 3%w/w, 0%w/w to 5%w/w MFGM albumen and the ganglioside of 1%w/w to 3%w/w, or

The protein of (e) 10%w/w to 15%w/w, the lipid of 80%w/w to 95%w/w, the phosphorus of 60%w/w to 80%w/w Fat, the phosphatidylcholine of 10%w/w to 20%w/w, the PHOSPHATIDYL ETHANOLAMINE of 18%w/w to 28%w/w, 10%w/w to 20% The sphingomyelins of w/w, the Phosphatidylserine of 4%w/w to 12%w/w, the phosphatidylinositols of 2%w/w to 10%w/w, 0%w/w To MFGM albumen and the ganglioside of 1%w/w to 5%w/w of 5%w/w, or

The lipid of (f) 75%w/w to 99%w/w, the phospholipid of 15%w/w to 35%w/w, the phosphatidyl of 5%w/w to 15%w/w Choline, the PHOSPHATIDYL ETHANOLAMINE of 5%w/w to 15%w/w, the sphingomyelins of 4%w/w to 15%w/w, 0.1%w/w to 2%w/w Phosphatidylserine and the phosphatidylinositols of 0.1%w/w to 2%w/w, or

The lipid of (g) 75%w/w to 95%w/w, the phospholipid of 50%w/w to 90%w/w, the phosphatidyl of 10%w/w to 45%w/w Choline, the PHOSPHATIDYL ETHANOLAMINE of 12%w/w to 25%w/w, the sphingomyelins of 12%w/w to 25%w/w, 1%w/w to 6%w/w Phosphatidylserine and the phosphatidylinositols of 0.5%w/w to 4%w/w, or

The lipid of (h) 80%w/w to 90%w/w, the phospholipid of 65%w/w to 75%w/w, the phosphatidyl of 10%w/w to 30%w/w Choline, the PHOSPHATIDYL ETHANOLAMINE of 12%w/w to 22%w/w, the sphingomyelins of 12%w/w to 22%w/w and 1%w/w to 3%w/w Phosphatidylserine, or

The lipid of (i) 25%w/w to 45%w/w, 10%w/w to 30%w/w phospholipid, the phosphatidyl gallbladder of 2%w/w to 5%w/w Alkali, the PHOSPHATIDYL ETHANOLAMINE of 3%w/w to 7%w/w, the sphingomyelins of 2%w/w to 5%w/w, the phospholipid of 2%w/w to 12%w/w Acyl serine, the phosphatidylinositols of 1%w/w to 5%w/w and the ganglioside of 0.2%w/w to 1%w/w, or

The lipid of (j) 20%w/w to 40%w/w, 5%w/w to 30%w/w phospholipid, 1%w/w to 5%w/w phosphatidylcholine, The PHOSPHATIDYL ETHANOLAMINE of 2%w/w to 8%w/w, the sphingomyelins of 0.5%w/w to 5%w/w, the phosphatidyl of 1%w/w to 10%w/w Serine, the phosphatidylinositols of 1%w/w to 6%w/w and the ganglioside of 0.8%w/w to 3.5%w/w.

17. purposes as claimed in claim 1, it also includes respectively, uses lactoferrin simultaneously or sequentially.

18. purposes as claimed in claim 1, wherein become infant formula or growth milk replacer by described preparation of reagents.

19. purposes as claimed in claim 1, wherein become bigger infant formula by described preparation of reagents.

Purposes as described in any claim in 20. such as claim 1 to 19, wherein said CLA is cis-9, trans-11CLA or its Salt.

Purposes as described in any claim in 21. such as claim 1 to 19, the butterfat of wherein said high CLA comprises 2 to 50% Cis-the 9 of weight ratio, trans-11CLA or its salt.

22. purposes as claimed in claim 21, wherein said high CLA butterfat comprises cis-the 9 of 4%-50% weight ratio, trans- 11CLA。

23. purposes as claimed in claim 21, wherein said high CLA butterfat comprises cis-the 9 of 4%-7% weight ratio, trans- 11CLA。

24. purposes as claimed in claim 21, wherein said high CLA butterfat comprises cis-the 9 of 6%-50% weight ratio, trans- 11CLA。

25. purposes as according to any one of claim 1-19, wherein said CLA is 9,11-octadecadienoic acid and 10, 12-octadecadienoic acid, or its salt, or above-mentioned mixture.

26. purposes as according to any one of claim 1-19, wherein said high CLA butterfat includes CLA isomer, described CLA isomer comprises cis-the 9 of at least 50% weight ratio, trans-11CLA, or its salt.