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WO1997035490A1 - Supplement alimentaire au colostrum - Google Patents

Supplement alimentaire au colostrum Download PDF

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Publication number
WO1997035490A1
WO1997035490A1 PCT/AU1997/000192 AU9700192W WO9735490A1 WO 1997035490 A1 WO1997035490 A1 WO 1997035490A1 AU 9700192 W AU9700192 W AU 9700192W WO 9735490 A1 WO9735490 A1 WO 9735490A1
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WO
WIPO (PCT)
Prior art keywords
colostrum
neonates
supplement
serum
neonatal
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/AU1997/000192
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English (en)
Inventor
Lance William Smith
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Thermo Trace Pty Ltd
Original Assignee
Trace Scientific Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Trace Scientific Ltd filed Critical Trace Scientific Ltd
Priority to NZ332151A priority Critical patent/NZ332151A/xx
Priority to AU21432/97A priority patent/AU2143297A/en
Publication of WO1997035490A1 publication Critical patent/WO1997035490A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/14—Blood; Artificial blood
    • A61K35/16—Blood plasma; Blood serum
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K20/00—Accessory food factors for animal feeding-stuffs
    • A23K20/10—Organic substances
    • A23K20/142—Amino acids; Derivatives thereof
    • A23K20/147—Polymeric derivatives, e.g. peptides or proteins
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K50/00—Feeding-stuffs specially adapted for particular animals
    • A23K50/60—Feeding-stuffs specially adapted for particular animals for weanlings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A61K39/39516—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum from serum, plasma

Definitions

  • This invention relates to food supplements for animals and in particular, to colostrum food supplements for neonatal animals. It also relates to methods of treatment of diseases caused by enteropathogens in animals, and in particular to the treatment of scours in pigs. BACKGROUND OF THE INVENTION
  • Neonates When neonates are born, they lack natural defence mechanisms to disease and infection. Neonates receive protection from diseases and infections by ingesting colostrum from their mother which contains antibodies required to protect them until their own immune system is functioning effectively.
  • Antiserums are generally derived from adult animals and have poor concentrations of immunoglobulins ("Ig"), an inappropriate ratio of IgG: IgA and IgG subgroups, are difficult to administer and transport and raise questions of disease transfer.
  • Antibiotics are expensive to produce, lead to resistant disease agents, have a systemic component to their mode of action and thus will lead to the host tissue including drug residue for a period of time after treatment thereby preventing commercial sale of the animal carcass during that period.
  • Vaccines are generally best administered to adult animals and do not adequately deal with the issues of milk and nutrient deprived neonates or individuals that already exhibit disease symptoms.
  • Conventional immune supplements are either too low in concentration or need to be administered in high volume to be effective. Often the immunoglobulin ratio is inappropriate unless the supplements are individually tailored. Additionally it is difficult to maintain the activity of the immunoglobulins in such supplements throughout the isolation and purification process without the use of solvents or heat.
  • colostrum substitute products There are many colostrum substitute products currently available that claim to aid the survival of new born domestic livestock.
  • the main claim of these products is to provide a source of immunoglobulins to supplement passive immunity transfer from the mother, and also to provide some nutrients such as proteins, carbohydrates, lipids, and often minerals in the form of sodium, potassium and calcium salts.
  • the products available range from dried adult serum supplemented with oils as an immediate source of energy delivered as a paste, spray dried adult serum supplemented with dry feed and dairy milk and whey powders which are a by-product of either dairy production.
  • Whey based products consist of adult immunoglobulin, bovine serum albumins, lactalbumin, lactoglobulin, lactose and minerals.
  • the whey protein concentrate is obtained from hyperimmunised adults so that the colostrum supplement product contains some enhanced level of immunoglobulins for a specific group of disease organisms.
  • Such products exhibit the disadvantage of consisting of adult immunoglobulins sourced from milk, rather than immunoglobulins in the types and ratios required by a neonatal animal.
  • An example of this type of product is disclosed in US 5,066,491.
  • a whey based product which is derived from ordinary milk is used to provide positive immunity transfer from adult cows. Similar treatments are described in US 4,816,252 and US 4,834,974.
  • Serum derived colostrum substitutes are available in a range of products, from pastes with oil added, to water soluble formulated products. Some of these products contain hyperimmune sheep serum, whey powder, dextrose and also serum derived colostral immunoglobulins. However, such products do not provide the preferred types and ratios or immunoglobulins required by neonatal animals. Furthermore, most of these products are simply spray dried adult serum which is added to feed as a bulk protein additive. These products do not generally show high immunoglobulin activity and as such act as a protein source rather than an immunoglobulin source.
  • JP 61289845-A discloses a substitute feed for piglets and calves which is constituted from the dry powder of blood serum of pigs or cattle and a base component which may be powdered milk, fat and oil, sugar, vitamins or minerals.
  • This type of product suffers the disadvantage that the immunoglobulins present are suited to adult animals and thus are not present in the types and concentrations required for neonates nor particularly for diseased animals.
  • Another example is described in GB 2289278 which is directed to a product for and method of treating the failure of passive immunity transfer.
  • the product is prepared from bovine colostrum and once modified to remove the casein and fat, is prepared in serum form for injecting into a calf.
  • AU 87701/82 also discloses the use of the milk of immunised mammals to provide extra antibodies specific to endotoxins.
  • the mammals are immunised against various toxins and the resulting milk is used to treat neonates which are not receiving adequate amounts of the resulting antibodies.
  • US 4,971 ,974 discloses a similar method.
  • an object of this invention to provide an improved colostrum supplement for neonatal animals that does not exhibit the above mentioned disadvantages. It is also an object of this invention to provide an improved colostrum supplement for neonatal animals which improves their chance of survival when they cannot obtain sufficient colostrum from their mother. It is a further object of the invention to provide a method of treatment of enteropathogenic disease in animals, and in particular an effective treatment of scours in pigs.
  • This invention therefore provides an improved colostrum supplement including neonatal serum from neonates which have suckled maternal colostrum.
  • a composition for use in the treatment of enteropathogenic diseases in animals comprising neonatal serum from neonates which have suckled maternal colostrum, preferably in adjunct with pharmaceutically or veterinarally acceptable carriers and excipients.
  • the serum for both aspects of the invention is sourced from neonatal calves. It is further preferred that the neonatal calf serum is obtained from calves slaughtered before 6 days of age. It is also preferred that the neonatal serum has at least 25% w/w immunoglobulins on a total protein basis. As an alternative to including neonatal serum directly into the supplement of the invention, the immunoglobulin content of the neonatal calf serum may be isolated and incorporated into the supplement directly.
  • the composition comprising the colostrum supplement of the instant invention is suitable for all neonates particularly calves, piglets, sheep and also humans. The colostrum supplement will also be suitable for any other mammalian neonate lacking access to sufficient maternal colostrum. The colostrum supplement is also useful for other neonates such as fish, reptiles and crustaceans, providing a source of immunity to infection as well as suitable energy sources.
  • the neonatal serum from which the supplement is derived has a high titre of a relevant mix of immunoglobulins maintaining their native function including alimentary active IgA so as to closely mimic natural colostrum. It is furthermore found that this product, when it is used in the treatment of diseased animal, acts at the site of the disease being the gut wall thereby maximising its efficiency without systemic action. The product passes harmlessly through the treated animal without leaving undesirable residues. It is preferred that the colostrum supplement or composition contains from 5 to 100% w/w neonatal serum immunoglobulins. More particularly, the supplement will contain from 20 to 70% w/w neonatal serum immunoglobulins.
  • the colostrum supplement or composition will also preferably contain other components such as carbohydrates.
  • the carbohydrates are preferably sourced from whey protein concentrate and are present in the supplement in a concentration between 0 and 95% w/w. More preferably, carbohydrate will be present between 30 and 90% w/w.
  • the carbohydrates provide a readily available energy source for the neonate.
  • Dextrose is also preferably present in the colostrum supplement in an amount between 0 and 95% w/w. A more preferred amount of dextrose is between 10 and 40% w/w. Dextrose is included in the colostrum supplement to assist in preventing agglomeration of the powder and to provide a further form of carbohydrate.
  • the colostrum supplement or composition contains protein. These are present in the whey protein concentrate and assist in stabilising the immunoglobulin preparation. They also provide a source of amino acids for nutritional purposes.
  • Iron is also preferably included in the colostrum supplement or composition according to the second aspect of the invention. It is generally provided in the form of ferratin which is present from 0 to 5% w/w in the colostrum supplement or composition. Furthermore, it is preferable to have salts and minerals present in the colostrum supplement. Calcium, potassium and sodium are present in whey protein concentrate and can assist in rehydrating the neonate if necessary.
  • the colostrum supplement or composition according to the second aspect of the invention includes bile acids to aid digestion and act as a bacteriostat.
  • Bile acids are preferably present in an amount between 0 and 50% w/w. A more preferred amount is between 10 and
  • the colostrum supplement or composition according to the second aspect of the invention of the instant invention is manufactured as a powder and is then formulated into a liquid before use.
  • the preferred diluent is a salt solution which may also include an appropriate preservative.
  • the invention also provides a method of treating neonates requiring a colostrum supplement with a colostrum supplement including neonatal serum from neonates which have suckled maternal colostrum.
  • a method of treatment of enteropathogenic diseases in animals comprising administering to animals requiring such a treatment an effective amount of a composition including neonatal serum from neonates which have suckled maternal colostrum.
  • the method of this embodiment of the invention is particularly effective in the treatment of scours in animals, and most particularly, in the treatment of scours in pigs.
  • the neonates or diseased animals are treated with a colostrum supplement or composition which comprises immunoglobulins sourced from the neonatal calf serum, the calves from which the serum or immunoglobulins have been sourced should have been slaughtered before 6 days of age.
  • the neonates or diseased animals are treated with a colostrum supplement including one or more of carbohydrates, protein, dextrose, salts, minerals, iron and bile acids.
  • a colostrum supplement including one or more of carbohydrates, protein, dextrose, salts, minerals, iron and bile acids.
  • the preferred colostrum supplement contains a range of immunoglobulins derived from colostrum, but sourced from new born calf blood. It also preferably contains whey protein, carbohydrate in the form of lactose and dextrose, minerals, iron and bile salts. Each of these components assist the neonatal infant to fight disease and infection and also to grow in the early days after birth when parental colostrum is unavailable or insufficient. Whilst adult immunoglobulins have been used in colostrum supplements, they have usually failed to protect neonates adequately because the adult animal is too healthy and does not contain the full compliment of neonatal immunoglobulins.
  • the immunoglobulins for the colostrum supplement are sourced from new born calf blood. Analysis of newborn calf blood shows that the immunoglobulin level is very high compared to adult animals or older calves. Because the calf is taking maternal mucosal immunoglobulins through colostrum, the calves blood is enriched in these immunoglobulins. Immediately after birth, the calves immune system is making very little if any of its own immunoglobulins. As the small intestine of neonates is incompetent to large molecules such as immunoglobulins, the immunoglobulin levels rise rapidly from about 45 - 50 mg/litre at birth to 34 - 35 gm/litre as soon as the calf takes in colostrum.
  • the composition of the immunoglobulins in the neonatal blood reflects the colostrum they are absorbed from, with a very high relative level of lgG1 (97.5%) to lgG2 and also very high levels of IgA and IgM compared to a mature animal.
  • These passive immunoglobulins are very active against enteric bacteria that infect neonates such as E. coli and Clostridium. Colostrum-derived immunoglobulins are also effective against other infective agents such as rotavirus.
  • the immunoglobulins of the supplement appear to transfer passive immunity to the neonatal animal and also become involved in direct agglutination between pathogens and the immunoglobulins in the gut of the neonatal animal.
  • the neonatal animal also acts as a filter and only brings into its system preferentially the immunoglobulins most likely to protect itself from disease states and thereby concentrating the most useful immunoglobulins.
  • the agglutination occurring in the calves gut would only deplete a very insignificant amount of the available immunoglobulin from the colostrum. Most of the useful immunoglobulins would be taken into the blood stream by the calf.
  • the colostrum supplement also preferably contains carbohydrates generally sourced from whey protein concentrate.
  • This concentrate consists of whey proteins and lactose in the form of whey powder.
  • the whey powder can be replaced or combined with casein, sodium caseinate, whole or skim milk powder, soya protein powder, soluble soya protein, soluble fish meal, blood powder, serum powder, plasma powder, bovine serum albumin, egg albumin, egg powder, lactalbumin, lactoglobulin or any soluble protein that can be used to stabilise immunoglobulins in solution.
  • the whey protein concentrate acts as an anticaking agent, helping the colostrum supplement remain a free flowing powder in storage.
  • the sugars in the colostrum supplement are immediately available to the neonatal animal upon dosing, thus providing an immediate source of energy to starving individuals and reducing the chance of death due to hypothermia.
  • the extra dose of carbohydrate will also aid piglets suckling on alactic milk in instances when the mother cannot or does not produce a reasonable source of carbohydrate.
  • This energy source is much needed in the case of piglets or lambs suffering hypothermia soon after birth.
  • the neonate will lose any desire to feed and die rapidly.
  • the carbohydrate in the colostrum supplement leads to a rapid increase in body temperature to normal, followed by a stronger desire to feed and suckle.
  • the colostrum supplement may also contain dextrose.
  • Dextrose can be replaced or combined with lactose, dextrin, glucose, fructose or any easily assimilated soluble sugar or carbohydrate. Both the whey protein concentrate and the dextrose aid in keeping the powder from agglomerating when the powder is added to water and thus they improve the solubility of the colostrum supplement.
  • the dextrose and other sugars also provide a useful source of sugar for the neonate.
  • Proteins are also preferably present in the colostrum supplement.
  • proteins present in the whey protein concentrate such as lactalbumin, lactoglobulin, bovine serum albumin and immunoglobulins.
  • the immunoglobulins will supplement the immunoglobulins already present from the neonatal calf serum.
  • the proteins also help stabilise the immunoglobulin preparation and ensure the bioactive proteins remain stable both in solution and when they pass into the neonatal digestive system and gut.
  • the non-immunoglobulin proteins will also act as a source of protein and amino acids for nutritional purposes. These proteins also carry some iron into the neonatal animal's system via iron chelates and some mineral salts bound up in the protein such as calcium, and magnesium.
  • Salts and minerals are also preferably present in the colostrum supplement.
  • Calcium, potassium and sodium salts are present in the whey protein concentrate in reasonably high levels. These are important for the neonatal animal in instances where the disease state such as gut related infections cause some dehydration. Minerals provided in the colostrum supplement will help to maintain the neonates salt balance when the animal is rehydrated.
  • Iron is also a preferable component of the colostrum supplement. It is preferably provided in the form of iron saturated ferratin.
  • Ferratin is the major iron storage protein found in the liver, spleen and intestinal mucosa on animals and it is widely distributed in the plant and animal kingdom. The protein is about 20% iron by weight and is very soluble in water and saline. Suitable alternatives to ferratin are hemin, transferrin or lactoferrin or any protein containing a relatively high proportion of iron bound ionically or by chelation in its protein structure.
  • suitable iron sources are iron sulphate or a casein: iron chelate or any other iron complex with protein which can be easily assimilated. Iron is important for neonatal animals as rapidly growing neonatal animals require and utilise iron during development and serum levels can fall to dangerously low levels causing ill thrift and reducing the animal's growth rate. Metabolic problems can also occur when iron is deficient.
  • Bile acids as their sodium or acid forms, or a mixture of base and acids can be included in the colostrum supplement to acid digestion and to act as a bacteriostat.
  • This particular component is particularly useful in fish feeding where the colostrum supplement can be used to prevent infections in young or growing fish or farmed marine life such as prawns.
  • the colostrum supplement is prepared as a powder and is then formulated into a liquid before use.
  • the preferred diluent is a salt solution which may also include an appropriate preservative. Water or phosphate buffered saline could also be used.
  • the colostrum supplement can be compounded with feeding meal.
  • a preferred formulation according to the invention is as follows:
  • Component % w/w calf serum derived immunoglobulins 38 crude bile acids (70% bile acids) 35 whey protein 27
  • a particularly preferred formulation of the improved colostrum supplement is as follows:
  • the colostrum supplement is prepared as a 25% w/v solution.
  • the required quantity of finished product is determined and from this the volume of solution required is calculated.
  • the required volume of water is purified by ultrafiltration and stored in tanks which have been sanitised with water at 95 C for one hour, followed by hydrogen peroxide solution at 250ppm for an hour. The tanks are drained and all residues allowed to dissipate before use.
  • the appropriate quantities of dry ingredients are weighed into one of the sanitised tanks, with approximately 3/4 of the final volume of water. The mixture is left under agitation until dissolved, then the volume is made up to the required level.
  • the dry ingredients include serum derived newborn calf immunoglobulins which have been extracted from neonatal calf serum by standard protein extraction techniques.
  • the whey powder is sourced from the processing of milk. Dextrose monohydrate and ferritin are sourced from appropriate manufacturers.
  • the solution is transferred to sanitised trays and placed in the freeze-dryer where it remains until the product is dry.
  • the colostrum supplement is preferably prepared by dissolving and drying, rather than dry-blending to ensure that the finished product is completely homogeneous.
  • the dried product is recovered from the freeze dryer and stored in double bags and fibre drums.
  • Samples are taken and analysed for protein, ash, moisture, carbohydrate and microbial content.
  • Product which conforms to specification is ground to a fine powder to increase solubility, then packaged into bottles.
  • the bottles are labelled and packaged with the diluent.
  • the diluent consists of an aqueous saline solution with a suitable preservative such as methyl paraben or one of its derivatives as a preservative.
  • a suitable preservative such as methyl paraben or one of its derivatives as a preservative.
  • An appropriate volume of water is purified through ultrafiltration and stored in sanitised tanks.
  • Sufficient sodium chloride is weighed out to give a 0.9% w/v solution and dissolved in the water.
  • Sufficient methyl paraben is dissolved in a small volume of absolute ethanol and this solution is in turn added to the saline solution to give a final methyl paraben concentration of 0.1% w/v.
  • Example 1A The same formulation as listed in Example 1A can also be manufactured from neonatal calf serum rather than isolated neonatal calf serum immunoglobulins. In this case one litre of neonatal calf serum (42g of immunoglobulins and 28g of other proteins) is added to 23.34g of dextrose, 45g of whey protein and 1.15g of ferratin. The product is prepared in solution as described in Example 1A then freeze or spray dried.
  • Example 2 Preparation of Colostrum Supplement for Use
  • the colostrum supplement is provided in a two pack formulation.
  • One pack contains the dried supplement and the other contains the diluent.
  • the material is stable for at least 2 years.
  • Example 3 Administering Colostrum Supplement to Piglets As soon as possible after birth, but up to 36 hours after birth, administer one dose of 3ml of colostrum supplement to each piglet. For weak piglets suffering from starvation and hypothermia, two or three doses at two hourly intervals may be necessary.
  • Example 4 Trial Results The above colostrum supplement was formulated as in Examples 1A and
  • the final dosage used on piglets contained about 170mg of immunoglobulin in 3mls.
  • Taiwanese pig unit The data from Taiwanese field trials may be summarised as follows:
  • Calf antibodies from a product according to example 1A were tested against strains of E. coli serotype-O: 9, 101 and 149, and Rotavirus Porcine G5 (TFR 41) and G3 (CRW-8).
  • Antibodies at levels found in the product according to example 1A and colostrum were used to establish the level of agglutination between the antibodies and the most common serotypes of E. coli that cause scours in piglets and other newborns. Agglutination and inactivation (pathogen death) were measured for each of the E. coli serotypes against the Trace antibodies.
  • composition according to the invention exhibited agglutination activity against all three serotypes of E. coli associated with porcine scours, as seen in Table 1. This antibody activity was also consistent with results observed in functional growth inhibition, as shown in Table 2. As expected, the strongest activity was directed against serotype O:101.
  • Rotavirus strains were cultured in MA-104 cells with the use of trypsin in serum-free medium.
  • Appropriate fluorescein conjugated antibodies were used to determine the presence of Rotavirus in the infected cells.
  • Plaque reduction (fluorescent focus reduction) assays were used to determine the level of neutralising antibodies. Table 3
  • compositions comprising immunoglobulins in the form of neonatal calf serum, or as an extract therefrom are well suited to the treatment of enteropathogenic diseases in animals, in particular, the treatment may be administered orally rather than by injection making effective delivery a simple matter, transport and storage are simple, the regimen is cost effective and moreover the composition need only be administered in a low, residue-free dose to achieve efficacy.
  • calves are not the only neonates from which it is possible to source neonatal serum or serum-derived immunoglobulins since many animal neonates suckle from their mothers in their infancy.
  • compositions derived from the sera of other domestic livestock including lambs, piglets and kids.

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Abstract

Supplément au colostrum comprenant un sérum néonatal prélevé chez des nouveau-nés qui ont consommé du colostrum maternel. L'invention décrit aussi une composition à utiliser pour le traitement d'affections entéropathogènes chez des animaux, comprenant du sérum néonatal prélevé chez des nouveau-nés qui ont consommé du colostrum maternel, de préférence en association avec des vecteurs et excipients acceptables sur le plan pharmaceutique ou vétérinaire. De préférence, le sérum provient de veaux nouveau-nés. Mieux encore, le sérum provient de veaux tués avant l'âge de 6 jours et contient au moins 25 % en poids d'immunoglobulines par rapport à la teneur totale en protéines. Comme solution de remplacement du sérum néonatal, on peut isoler les immunoglobulines présentes dans le sérum de veau nouveau-né et les intégrer directement dans le supplément. Cette composition ou ce supplément convient pour tous les nouveau-nés, en particulier bovins, porcins, ovins et aussi humains, et pour tous les mammifères nouveau-nés qui ne peuvent pas accéder à un colostrum maternel en quantité suffisante.
PCT/AU1997/000192 1996-03-26 1997-03-25 Supplement alimentaire au colostrum Ceased WO1997035490A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
NZ332151A NZ332151A (en) 1996-03-26 1997-03-25 Colostrum food supplement containing immunoglobulin from neonatal calves
AU21432/97A AU2143297A (en) 1996-03-26 1997-03-25 Colostrum food supplement

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
AUPN8905A AUPN890596A0 (en) 1996-03-26 1996-03-26 Colostrum food supplement
AUPN8905 1996-03-26

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WO1997035490A1 true WO1997035490A1 (fr) 1997-10-02

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AU (1) AUPN890596A0 (fr)
CA (1) CA2250211A1 (fr)
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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000024266A3 (fr) * 1998-10-26 2000-07-13 Galagen Inc Compositions a base de soja et d'immunoglobulines
WO2009092383A3 (fr) * 2008-01-22 2009-10-01 Multimerics Aps Produits et méthodes pour prévenir une infection
CN117750889A (zh) * 2021-02-26 2024-03-22 潘思瑞公司 稳定的初乳组合物

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CN1078389A (zh) * 1992-05-14 1993-11-17 杭州四季青生物工程材料研究所 无支原体新生牛血清生产工艺

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Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000024266A3 (fr) * 1998-10-26 2000-07-13 Galagen Inc Compositions a base de soja et d'immunoglobulines
WO2009092383A3 (fr) * 2008-01-22 2009-10-01 Multimerics Aps Produits et méthodes pour prévenir une infection
US8475789B2 (en) 2008-01-22 2013-07-02 Multimerics Aps Products and methods to prevent infections
US9259440B2 (en) 2008-01-22 2016-02-16 Multimerics Aps Methods for passive immunization
CN117750889A (zh) * 2021-02-26 2024-03-22 潘思瑞公司 稳定的初乳组合物

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