CN101505767B - Agent for preventing infection - Google Patents
Agent for preventing infection Download PDFInfo
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- CN101505767B CN101505767B CN200780029115.1A CN200780029115A CN101505767B CN 101505767 B CN101505767 B CN 101505767B CN 200780029115 A CN200780029115 A CN 200780029115A CN 101505767 B CN101505767 B CN 101505767B
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- Prior art keywords
- flu
- viral infection
- sphingomyelins
- fat
- phospholipid
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Landscapes
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
An agent for preventing infection of influenza virus or a food and drink for preventing infection of influenza virus is provided. The agent for preventing infection of influenza virus and food and drink for preventing infection of influenza virus containing a fat globule membrane component as an active ingredient. The agent for preventing infection of influenza virus and food and drink for preventing infection of influenza virus containing a phospholipid with sphingosine and/or a derivative thereof, particularly sphingomyelin as an active ingredient.
Description
Technical field
The present invention relates to the medicament of flu-prevention viral infection, the fatty ball film component of described kit is as active component.
In addition, the invention still further relates to the medicament of flu-prevention viral infection, described medicament comprises the phospholipid that contains sphingol and/or its derivant, particularly sphingomyelins as active component.
Background technology
Influenza virus infects the people by air, thereby almost all causes popular every year.Although because the improvement of health measure and its threat of progress of medical science reduce, still have the dead situation that causes in recent years.
The influenza virus that has A type, Type B and C type three types, wherein A type virus is easy to produce variation and is easy to cause worldwide flu outbreak.Mainly come the flu-prevention Viral infection by vaccination.Yet, because influenza virus is easy to cause the variations such as antigenic shift, antigenic drift, so the antigen of epidemic virus and vaccine is also inconsistent in many cases, carry out preventive effect and not satisfied situation so that exist by vaccine at present.
Therefore, present prophylactic vaccination for the child is not obligatory yet.Amantadine, oseltamivir (oseltamivir) etc. are used as the therapeutic agent of influenza, but owing to need to consider the problems such as appearance of side effect, resistant bacterium, so must be noted that their use.In view of the situation, people have begun to pay close attention to and can absorb safely daily and effectively reagent or food or the beverage of flu-prevention viral infection.
Summary of the invention
The medicament that the purpose of this invention is to provide the flu-prevention viral infection, described medicament can be by daily safety picked-up.
The newborn constituents that has various physiologically actives by concern, the inventor has carried out in depth research to them for the preventive effect of influenza infection, and phospholipid and/or its derivant having found fat globule membrane component and contained sphingol have preventive effect for influenza infection, therefore cause having finished the present invention.
That is, the present invention relates to following content.
(1) a kind of medicament of flu-prevention viral infection, the fatty ball film component of described kit is as active component.
(2) a kind of medicament of flu-prevention viral infection, described medicament comprise the phospholipid that contains sphingol and/or its derivant as active component.
(3) according to the medicament of (2) described flu-prevention viral infection, the wherein said phospholipid that contains sphingol is sphingomyelins.
(4) a kind of food or beverage for the flu-prevention viral infection, the fatty ball film component of described food or beverage packets.
(5) a kind of food or beverage for the flu-prevention viral infection, described food or beverage comprise phospholipid and/or its derivant that contains sphingol.
(6) according to (5) described food or beverage for the flu-prevention viral infection, the wherein said phospholipid that contains sphingol is sphingomyelins.
Medicament by flu-prevention viral infection of the present invention and be used for food or the beverage of flu-prevention viral infection can the flu-prevention viral infection.
Because the medicament of flu-prevention viral infection of the present invention and be used for the food of flu-prevention viral infection or the fatty ball film component of beverage packets as active component, so they can relatively inexpensively be supplied with in a large number, and they also have the quite high characteristic of safety.
In addition, because the medicament of flu-prevention viral infection of the present invention and be used for the food of flu-prevention viral infection or beverage comprises the phospholipid that contains sphingol and/or its derivant, particularly sphingomyelins as active component, so they can relatively inexpensively be supplied with in a large number, and they also have the quite high characteristic of safety.
The specific embodiment
(fat globule membrane component)
The present invention relates to the medicament of flu-prevention viral infection, the fatty ball film component of described kit is as active component, and the invention still further relates to such food or beverage, described food or beverage are by mixing the effect with flu-prevention viral infection with fat globule membrane component.
Fat globule membrane component is the film that covers by the butter oil ball of mammary gland secretion, and it not only has makes fat be dispersed in effect in the milk, and has the many physiological actions as the food of new born animal.The milk fat ball film of milk comprises the protein of about 45 quality % and the lipid of about 55 quality %, and contain be called as lactomucin the macromolecule glycoprotein as protein.In addition, also contain the phospholipid of the triglyceride of the 70 quality % that have an appointment, about 27 quality % and the cholesterol of about 3 quality % etc. as lipid.
About the milk fat ball film of milk, known its has the protection milk fat ball film, makes the butter oil emulsion-stabilizing, promotes the digestion of lipid, the effects such as infection of defence specific bacteria.On the other hand, that separates from the mucosal tissue of animal contains activity (Biochem.J., 277, the 713-718 that a large amount of sialic mucin have resisiting influenza virus, 1991), but the composition of its composition is fully different from milk fat ball film composition according to the present invention.
As the Oil globule constituent of the film that uses among the present invention, for example can directly use such buttermilk, this buttermilk is to obtain when the butterfat that obtains with mammiferous milk such as centrifugalize milch cow such as churns is processed to prepare butter granule.
In addition, thereby by process such butterfat preparation butter granule with churn etc., thus obtained buttermilk also can be used as the Oil globule constituent of the film, wherein come from this butterfat, to remove without fat breast constituents by repeating the following process of several: come to mix and centrifugalize with this butterfat by the water that adds same amount, thereby make the butterfat with initial fat percentage.
In addition, when preparing butter oil by heating and the above-mentioned butter granule of centrifugalize, the butter serum that obtains as residue can be used as fat globule membrane component.
Therefore, owing in these buttermilks and butter serum, contain the fat globule membrane component of q.s, so these buttermilks and butter serum can directly be used as fat globule membrane component, but these buttermilks and butter serum can be further purified by methods such as dialysis, ammonium sulfate fractionated method, gel filtration, isoelectric point precipitation, ion exchange chromatography, solvent fractionation, ultrafiltration (UF), microfiltration methods (MF), thereby improve the purity of fat globule membrane component and use.
For example, for the compositions that the content that obtains fat globule membrane component increases, can use the separating and filtering technology by UF film or MF film.Because lipid part can not see through UF film or MF film, therefore can remove deproteinize, lactose and mineral.
The aperture of the molecular cut off of UF film and MF film there is no strict setting, and those skilled in the art can determine suitable value based on test.For example, in the situation of MF method, the tentative standard in aperture is 1.2 μ m or less, is preferably 0.2 μ m or less, and in the situation of UF method, the tentative standard of molecular cut off is 10,000 or larger, is preferably 50,000 to 100,000.
The compositions that the concentrated solution that filters can be increased with the content that makes fat globule membrane component by spray drying, the concentrated solution of perhaps processing through UF film or MF film can be by (the 100kg/cm that homogenizes
2Or higher), then through MF method or UF method process and spray drying with the further compositions of increase of the content that makes fat globule membrane component.
For example, can obtain according to following manner the rough part of fat globule membrane component.Combination by using ethanol, methanol isopolarity solvent and non-polar solven and polar solvent is (such as ether-ethanol (1: 3V/V), (2: 1V/V), chloroform-methanol-water (1: 2: 0.8V/V) etc.) processes the compositions that the content of fat globule membrane component increases, thereby extraction obtains crude fat to chloroform-methanol.By using acetone that this crude fat is carried out fractionated, can obtain to be rich in the insoluble part of acetone of fat globule membrane component.
In addition, butter serum (it is for being prepared the residue of butter oil by butterfat) contains a large amount of fat globule membrane component, so it is a kind of required material.Obtain crude fat by using ethanol from this butter serum, to extract, can use by utilizing acetone that this crude fat is carried out the product that fractionated obtains.In addition, can also use the extraction part (JP-A-7-173182) of the mixed solvent of hexane-alcohol-water.In addition, can also use fat globule membrane component derived from commercially available milk.
About at the medicament of flu-prevention viral infection of the present invention be used for the food of flu-prevention viral infection or the combined amount of the fat globule membrane component of beverage, in adult's situation, can regulate in such a manner the combined amount of fat globule membrane component, this mode is so that can absorb the fat globule membrane component of the amount of about 0.1mg to 5000mg every day.By being set in this scope, can bring into play the preventive effect for influenza infection.Because the fat globule membrane component as the active component of the medicament of flu-prevention viral infection of the present invention is newborn constituents, even therefore can say the problem that when huge uptake, also can not exist about aspect its safety.
(phospholipid that contains sphingol)
In addition, the invention still further relates to the medicament of flu-prevention viral infection, described medicament comprises the phospholipid that contains sphingol and/or its derivant, particularly sphingomyelins as active component, and the invention still further relates to such food or beverage, described food or beverage are by mixing the effect with flu-prevention viral infection with the phospholipid that contains sphingol and/or its derivant, particularly sphingomyelins.
Although there is the sphingomyelins of 20 to the 30 quality % account in a large number phospholipid in the Ruzhong, people still are limited to cellular level to the research of sphingomyelins effect, and the information of its physiological role in organism there is a serious shortage in the supply.Therefore, people do not recognize that yet it is as the effect of the composition of nutrient substance.
Application about sphingomyelins, known analgesic anti-inflammatory preparation for external application, lipid digest and assimilate the not enough disease therapeutic agent of function improving agent, intestinal tube motion function (JP-A-5-186330, JP-A-11-269074, JP-A-2003-252765) etc., but do not disclose the effect that it has the flu-prevention viral infection, thereby so that it is not used for the purpose of flu-prevention viral infection.
On the other hand, disclose for the composition (JP-T-2006-508045) (term used herein " JP-T " refers to the Japanese translation of disclosed PCT patent application) that has antivirus action by emulsifying and treated that antigen (JP-A-5-339169) as vaccine forms liposome and uses sphingomyelins as the situation of lipid components, but and do not known that sphingomyelins itself has the activity of resisiting influenza virus.
In addition, routine is known that ganglioside (it is contained glycolipid matter in the milk) has the activity (JP-A-4-105616) of influenza, but its constituent sialic acid is important for this effect, this effect is the function of expressing by such mechanism, wherein comprises the combination that sialic glycolipid matter suppresses virus and mucomembranous epithelial cell competitively.Therefore, clearly do not disclose the function that does not contain sialic sphingomyelins.
The phospholipid that contains sphingol of using among the present invention and/or its derivant, particularly sphingomyelins can be purification or can use with the form of the phospholipid that contains sphingomyelins.
Although be rich in sphingomyelins in animal brain and the newborn class fat, consider that from implementing viewpoint of the present invention newborn source sphingomyelins is expected.As newborn source sphingomyelins, expectation be to use lactogenesis, whey protein concentrate (WPC) etc. as material.
As the method for the phospholipid moiety that from lactogenesis, WPC etc., obtains to contain sphingomyelins, such as enumerating the method (JP-A-3-47192) of using ether or acetone to extract, using by heating and melt the conventional known methods such as the water-soluble portion that contains creamed curds or butter serum that butter obtains.By using the sphingomyelin content in the part that these materials and methods obtain to be respectively about 28 quality % and about 9 quality %.
In addition, come the above-mentioned phospholipid moiety that contains sphingomyelins of purification by technology such as dialysis, ammonium sulfate fractionated method, gel filtration, isoelectric point precipitation, ion exchange chromatography, solvent fractionation, ultrafiltration (UF), microfiltration methods (MF), can obtain the sphingomyelins that purity improves.
These sphingomyelins can optionally adopt the forms such as liquid, powder, sheet with the phospholipid that contains sphingomyelins, and can be directly Orally administered.In addition, not only sphingomyelins can be used, and the phospholipid composite of the lecithin that contains the effective dose that people's nutritional requirement limits can be used.
About at the medicament of flu-prevention viral infection of the present invention be used for food or the phospholipid that contains sphingol of beverage and/or the combined amount of its derivant of flu-prevention viral infection, in adult's situation, can regulate in such a manner combined amount etc., this mode is so that can absorb the phospholipid that contains sphingol and/or its derivant, the particularly sphingomyelins of the amount of about 0.1mg to 5000mg every day.By being set in this scope, can bring into play the preventive effect for influenza infection.Because the phospholipid that contains sphingol, particularly sphingomyelins as the active component of the medicament of flu-prevention viral infection of the present invention are newborn constituents, even therefore can say the problem that when huge uptake, also can not exist about aspect its safety.
As the dosage form of the reagent of flu-prevention viral infection of the present invention, such as enumerating tablet, capsule, granule, dusty material, powder agent, solution etc.These dosage forms can be Orally administered or can nasal administration.In addition, these dosage forms can prepare by the known universal method of routine.For example, they mix to form by preparing acceptable carrier, filler etc. with pharmaceutical preparation.
In addition, as food or the beverage with effect of flu-prevention viral infection of the present invention, such as can enumerate fat globule membrane component or phospholipid and/or its derivant and F﹠B or the various milk powder such as milk, newborn class beverage, coffee beverage, fruit juice, fruit jelly, cookies, bread, noodles, sausage and be intended to that the alimentation composition for nursing infant, baby, low birth weight infant etc. mixes those.Since can absorb them according to common mode, therefore can the flu-prevention viral infection.
The below illustrates the present invention in further detail with reference to embodiment and test example, but these explanations only are descriptive, and the present invention is not limited to this.
Embodiment 1
Process the butterfat that fat percentage is adjusted to 40 quality % with churn, and make it to be separated into butter granule and buttermilk.After this, by thus obtained buttermilk lyophilization is obtained fat globule membrane component.
Embodiment 2
Be adjusted to the water that adds same amount in the butterfat of 40 quality % to fat percentage, mix, prepare the butterfat that fat percentage is 40 quality % by centrifugalize, the such operation of triplicate is to remove from butterfat without fat breast constituents, then process such butterfat with churn, and make it to be separated into butter granule and buttermilk.After this, by thus obtained buttermilk lyophilization is obtained fat globule membrane component.
Embodiment 3
Be adjusted to the water that adds same amount in the butterfat of 40 quality % to fat percentage, mix, prepare the butterfat that fat percentage is 40 quality % by centrifugalize, the such operation of triplicate is to remove from butterfat without fat breast constituents, then process such butterfat with churn, and make it to be separated into butter granule and buttermilk.After this, use 50% saturated ammonium sulfate with processings of spending the night of this buttermilk, then centrifugalize is with the collection supernatant.After this, water is dialysed to thus obtained supernatant after, thereby lyophilization obtains highly concentrated fat globule membrane part.
[test example 1]
(Orally administered fat globule membrane component is come the checking of the effect of flu-prevention viral infection)
Use 1 * 10
3The influenza virus PR 8 (H1N1) of the virus quantity of pfu come infected mice (Balb/c, male, 6 the week ages).Before infect processing, the fat globule membrane component that obtains among the Orally administered embodiment 2, and judge its infection mitigation effect by the virus titer in 3 days posterula cleanout fluid of viral infection.Carry out Orally administered in, by the fat globule membrane component powder dissolution is come it is used in distilled water.In judgement, use plaque ethods (it uses mdck cell).
The results are shown in Table 1.Use in fat globule membrane component that the nasal cavity virus titer significantly reduces in the group.This shows that fat globule membrane component has the effect of flu-prevention viral infection.
[table 1]
Embodiment 4
Be partly dissolved in next solution for the preparation of the nasal cavity injection in the 200ml distilled water for injection by the concentrated fat globule membrane of height that 5g is obtained in embodiments of the invention 3.
Embodiment 5
With the material mixing of the prescription shown in the table 2, then granulation is filled in the capsule, thereby makes the capsule for the flu-prevention viral infection.
[table 2]
| Highly concentrated fat globule membrane part (embodiment 3) | (20.0 quality %) |
| Lactose | 24.5 |
| Soluble starch | 55.0 |
| Magnesium stearate | 0.5 |
Embodiment 6
With the material mixing of the prescription shown in the table 3, be filled in the container, heat sterilization then, thus make food or beverage for the flu-prevention viral infection.
[table 3]
| Highly concentrated fat globule membrane part (embodiment 3) | (2.5 quality %) |
| Sucrose | 7.5 |
| Citric acid | 0.6 |
| Sucus Mali pumilae | 10.0 |
| Water | 79.4 |
Embodiment 7
The reactant liquor that uses chloroform-methanol (2: 1) solution extraction to obtain by whey protein concentrate (WPC) aqueous solution that makes protease act on 10 quality %, concentrated, then use acetone further to extract, thereby obtain the complex lipid part.Then, process this complex lipid part with fluoro silicyl column chromatography, and progressively extract with chloroform-methanol solution, thereby obtain phospholipid moiety.Process this phospholipid moiety with silica gel chromatography, and progressively extract with chloroform-methanol solution, with the product lyophilization, thereby obtain sphingomyelins.Process this sphingomyelins with thin layer chromatography, then measure with the Dittmer reagent colour development and by optical densitometric method, thereby determine that sphingomyelin content is 95.2 quality %.Can directly use the sphingomyelins of in this manner acquisition as the medicament of flu-prevention viral infection.
[test example 2]
(checking of the effect of prevention A type influenza infection and Type B influenza infection)
Come per nasal infected mice (Balb/c as A type influenza virus or with B/Ibaraki virus as the Type B influenza virus with A/Guinzhou virus, male, 6 ages in week), the dosage of the solution of the sphingomyelins (SPM) that obtains in simultaneously take nasal cavity dosage as the embodiment 1 of the 100 μ g/ml of 5 μ l (dosage: 0.5 μ g) nasal administration, and judge that by the virus titer in the nasal cavity cleaning liquid it is for the preventive effect of influenza infection.Thus, make the group of using the independent per nasal of each influenza virus to infect.In judgement, use plaque ethods (it uses mdck cell).
The results are shown in Table 4.The result has confirmed to use sphingomyelins and has all had preventive effect for A type influenza infection and Type B influenza infection.Especially, confirm to have more significant effect for A type influenza virus.
[table 4]
[test example 3]
(Orally administered sphingomyelins comes the checking of the effect of flu-prevention viral infection)
Use 1 * 10
3The influenza virus PR 8 (H1N1) of the virus quantity of pfu come infected mice (Balb/c, male, 6 the week ages).Before infect processing, Orally administered sphingomyelins, and judge its infection mitigation effect by the virus titer in 3 days posterula cleanout fluid of viral infection.Carry out Orally administered in, by sphingomyelins is dispersed in water it is used.In judgement, use plaque ethods (it uses mdck cell).
The results are shown in Table 5.Use at sphingomyelins that the nasal cavity virus titer significantly reduces in the group.This shows that sphingomyelins has the effect of flu-prevention viral infection.
[table 5]
Embodiment 8
Be dissolved in next solution for the preparation of the nasal cavity injection in the 200ml distilled water for injection by the sphingomyelins that 5g is obtained in embodiment 7.
Embodiment 9
With the material mixing of the prescription shown in the table 6, then granulation is filled in the capsule, thereby makes the capsule for the flu-prevention viral infection.
[table 6]
| Sphingomyelins (embodiment 7) | (20.0 quality %) |
| Lactose | 24.5 |
| Soluble starch | 55.0 |
| Magnesium stearate | 0.5 |
Embodiment 10
Material mixing with prescription shown in the table 7 is filled in the container, heat sterilization then, thus make food or beverage for the flu-prevention viral infection.
[table 7]
| Sphingomyelins (embodiment 7) | (2.5 quality %) |
| Sucrose | 7.5 |
| Citric acid | 0.6 |
| Sucus Mali pumilae | 10.0 |
| Water | 79.4 |
Although with reference to its specific embodiments the present invention is explained, it will be apparent to those skilled in the art that and to make under condit without departing from the spirit and scope of the present invention various changes and modification.
Two Japanese patent applications (Japanese patent application No.2006-223276 and Japanese patent application No.2006-213273) that the application submitted to based on August 4th, 2006, its full content is incorporated herein by reference.
Claims (2)
1. the phospholipid that contains sphingol is for the preparation of the application in the medicament of flu-prevention viral infection.
2. according to claim 1 described application, the wherein said phospholipid that contains sphingol is sphingomyelins.
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2006213273A JP5202827B2 (en) | 2006-08-04 | 2006-08-04 | Infection preventive |
| JP2006213276A JP2008037789A (en) | 2006-08-04 | 2006-08-04 | Prophylactic agent for infection |
| JP213273/2006 | 2006-08-04 | ||
| JP213276/2006 | 2006-08-04 | ||
| PCT/JP2007/065171 WO2008016108A1 (en) | 2006-08-04 | 2007-08-02 | Agent for preventing infection |
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| Publication Number | Publication Date |
|---|---|
| CN101505767A CN101505767A (en) | 2009-08-12 |
| CN101505767B true CN101505767B (en) | 2013-01-02 |
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| Application Number | Title | Priority Date | Filing Date |
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| CN200780029115.1A Expired - Fee Related CN101505767B (en) | 2006-08-04 | 2007-08-02 | Agent for preventing infection |
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| JP (1) | JP5202827B2 (en) |
| CN (1) | CN101505767B (en) |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SE537951C2 (en) * | 2013-07-01 | 2015-12-01 | Hero Ag | Prophylactic use of infant formula for otitis |
| DE102018217334A1 (en) * | 2018-10-10 | 2020-04-16 | Harbins Ruhr Bioscience, Inc. | Sphingoid base and / or active ingredient for use in the prophylaxis and / or therapy of a viral infection and / or viral infectious disease or disinfection, food / food supplements, feed / feed supplements and crop protection agents |
| WO2022015348A1 (en) | 2020-07-16 | 2022-01-20 | Harbins Ruhr Bioscience, Inc. | Sphingoid compounds for use in prophylaxis and/or therapy of coronaviridae infection |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1363393A (en) * | 2002-01-19 | 2002-08-14 | 余内逊 | Process for preparing health-care compound sheep placenta extract food series |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP3581010B2 (en) * | 1998-03-18 | 2004-10-27 | 雪印乳業株式会社 | Lipid digestion and absorption function improver |
| JP2001233773A (en) * | 2000-02-22 | 2001-08-28 | Toko Yakuhin Kogyo Kk | Antiviral agent |
| JP3891536B2 (en) * | 2000-03-30 | 2007-03-14 | 明治乳業株式会社 | Oral composition containing phospholipids derived from mammalian milk |
| JP2003252765A (en) * | 2002-02-28 | 2003-09-10 | Snow Brand Milk Prod Co Ltd | Agent for treatment of intestinal movement insufficiency |
| JP2004002215A (en) * | 2002-05-23 | 2004-01-08 | National Institute Of Advanced Industrial & Technology | Method for producing sphingolipid derivative |
| AU2003254202A1 (en) * | 2002-07-30 | 2004-02-16 | Esperion Therapeutics, Inc. | Methods of using non-human animal apoliprotein a-i protein |
| JP4210744B2 (en) * | 2003-02-14 | 2009-01-21 | 独立行政法人産業技術総合研究所 | Sphingolipid derivatives |
| US20080317767A1 (en) * | 2004-04-08 | 2008-12-25 | Tobias Braxmeier | Tripartitle Raftophilic Strutures and their Use |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1363393A (en) * | 2002-01-19 | 2002-08-14 | 余内逊 | Process for preparing health-care compound sheep placenta extract food series |
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| CN101505767A (en) | 2009-08-12 |
| JP5202827B2 (en) | 2013-06-05 |
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