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    • 专利摘要:
    Protein hydrolysates are used to prevent bacterial overgrowth. It has also been found in suckling mammals that certain protein hydrolysates promote intestinal fungal patterns similar to those of mammals raised by mothers. Another advantage is that the hydrolyzate is simpler to administer and easier to obtain than to treat bacterial overgrowth with the help of the active ingredient.
    公开号:KR20040019092A
    申请号:KR10-2004-7001471
    申请日:2002-07-25
    公开日:2004-03-04
    发明作者:가르시아-로데-나스클라라엘；발레브르올리비에；로샤플로랑스
    申请人:소시에떼 데 프로듀이 네슬레 소시에떼아노님；
    IPC主号:
    专利说明:

    NUTRITIONAL COMPOSITION PREVENTING BACTERIAL OVERGROWTH}
    [1] The present invention relates to the use of nutritional compositions for the prevention of related diseases such as bacterial overgrowth, bacterial metastasis and necrotizing colitis, bacterial metastasis sepsis and / or reduced availability of nutrients. The invention also relates to a method of preventing or treating such a condition.
    [2] Bacterial overgrowth often occurs in premature infants, critically ill and elderly people and is one of the main causes of life-related diseases such as necrotic colitis, bacterial metastasis, sepsis and reduced availability of nutrients.
    [3] In the first stage of bacterial overgrowth, typically only colonic bacteria begin to migrate through the sclera and colonize the ileum. In later stages, even factories can be invaded. Typically, colonization of the small intestine by bacteria is even in the case of probiotic bacteria, such as certain Lactobacillus or Bifodobacterium strains, which, if present in the large intestine, can have a beneficial effect on the host. Harms the host
    [4] WO 200022945 (SOC PROD NESTLE SA) reports new proteins isolated from milk that have anti-inflammatory, antibacterial and anti-allergic properties and are useful for the prevention and treatment of inflammatory bowel disease, Crohn's disease, colitis and other diseases.
    [5] JP 08059500 (MORINAGA MILK IND CO LTD) teaches a mixture of novel peptides collected from lactoferrin hydrolysates with certain physiological and biological properties that prevent the transfer of intestinal bacteria from the intestine to other organs.
    [6] JP 05304929 (MORINAGA MILK IND CO LTD) discloses a method for ameliorating abnormal bacterial compositions of human or animal flora. Liquid or fluid foods according to JP 05304929 include bovine lactoferrin.
    [7] Typically, protein hydrolysates are known and are used in liquid formulations which primarily reduce the allergic properties of the corresponding intact protein. For example, milk protein hydrolysates are part of nutritional formulas for people with allergies to antigens of milk proteins.
    [8] To date, the problem of bacterial overgrowth has been addressed by drug treatment or, more recently, by other physiologically active substances (eg lactoferrin) that can also be isolated or purified from milk. Usually medication is not very advisable, because it means that it has a strong effect on the body and also affects the bacterial flora of the large intestine. Thus, drug treatment does not cure bacterial overgrowth, but kills the intestinal bacterial flora. A disadvantage of certain active ingredients which are also separated from milk is that they must be produced or isolated, their absorption must be formulated correctly, and finally, this can also cause side effects. In addition, these materials are typically only used to treat advanced bacterial overgrowth and are not used for prophylactic or less severe conditions.
    [9] Therefore, there is a need to easily produce a product for the treatment of bacterial overgrowth in its natural state, which does not involve expensive purification procedures, at the same time has nutritional value, and does not have side effects associated with drug treatment. In this sense, there is also a need for moderate treatment that does not interfere with bacterial growth in the large intestine, which may be desirable.
    [10] Finally, there is a need for nutrients for the preparation of nutritional compositions for suckling mammals that promote intestinal fungal patterns similar to those present in mammals raised by mothers.
    [11] There is also a need to provide flawless, food-based nutrition in place of medicaments or pharmacologically active substances.
    [12] The present invention addresses the problem of providing nutrition to patients suffering from bacterial overgrowth or metastasis in the intestine and other diseases that are closely related or a direct consequence of bacterial overgrowth. The present invention also has the object of providing flawless nutritionally valuable beneficial nutrients and food based nutrition.
    [13] It is also an object of the present invention to provide nutrients to patients suffering from bacterial overgrowth while reducing the use of pharmaceutically active substances as much as possible.
    [14] Summary of the Invention
    [15] Surprisingly, it has been found that certain protein hydrolysates prevent bacterial overgrowth in the small intestine, which promotes an enteric fungal pattern similar to that induced by breast milk.
    [16] Thus, as a first aspect, the present invention provides the use of protein hydrolysates for the preparation of nutritional compositions for the prophylaxis or treatment of bacterial overgrowth, necrotizing colitis, bacterial metastatic sepsis and / or reduced availability of nutrients.
    [17] As a second aspect, the present invention provides the use of a protein hydrolyzate for the preparation of a nutritional composition for the promotion or construction of a balanced and / or beneficial enteric flora pattern.
    [18] In a third aspect, the present invention provides a method for the prevention or treatment of bacterial overgrowth or bacterial metastasis, which comprises administering a nutritional composition containing protein hydrolysate.
    [19] As a fourth aspect, the present invention provides a method of preventing or treating necrotic colitis, sepsis and / or reduced availability of nutrients, which comprises administering a nutritional composition containing protein hydrolysate.
    [20] An advantage of the present invention is that it provides a simple, readily available and inexpensive means for effectively preventing or treating intestinal bacterial overgrowth and other pathogenic conditions associated therewith.
    [21] Another advantage of the present invention is that it provides the prevention of bacterial overgrowth and at the same time is nutritionally beneficial to the patient.
    [22] Another advantage of the present invention is that it is particularly suitable for the preparation of liquid formulations, such as intestinal formulations.
    [23] In the drawing,
    [24] 1 shows the molecular weight (MW) distribution of protein hydrolysates useful for practicing the present invention. Bars represent the percentage of total area measured at 220 nm corresponding to the indicated MW range. Lines show cumulative size distribution (% area vs MW). The median MW is 475 Da (= MD 50%).
    [25] Peptide profiles were evaluated by size exclusion high performance liquid chromatography (SEC-HPLC). Calibration curves of residence time versus molecular weight were prepared using known molecular weight pure proteins, peptides and amino acids (standard). Peptide bonds and aromatic rings of some amino acids were detected at a wavelength of 220 nm.
    [26] The vertical axis of FIG. 1 is named “% area at 220 nm”, reflecting the fact that the irregular surface of the chromatogram is divided into several sections, based on the reference residence time, each corresponding to a range of molecular weights. do. The surface of each section is divided by the total area (100%). This is the standard procedure for analyzing molecular weight distribution.
    [27] 2 is a plant of rats fed by a mother (MF, clear bar) or fed artificial diet (degree of hydrolysis (DH, see definition below) 0% and DH 30%, respectively filled and oblique bar) , Enterobacteria counts in the ileum and caecum. Mean ± standard error (± SEM) values are shown. Within the same chapter fragment, different letters mean significant differences.
    [28] 3 shows Enterococci counts. See the description of FIG. 2 for details.
    [29] 4 shows Lactobacilli counts. See the description of FIG. 2 for details.
    [30] The word "containing" herein means "including" among others. This should not be understood to mean "consisting of only."
    [31] The word “bacterial overgrowth” in the present invention also means a disease, discomfort or abnormal condition associated with or as a result of bacterial overgrowth. Sepsis and reduced availability of nutrients may be an example of this result.
    [32] In the present specification, the abbreviation “DH” means hydrolysis degree. This term is known in the art and, for proteinaceous materials, refers to the percentage of α-NH 2 -nitrogen relative to total nitrogen (the amount of nitrogen in the form of free amino nitrogen). Units (%) are often omitted for convenience, especially when using standard hydrolysates (eg, DH0 means free protein and DH30 means broadly hydrolyzed hydrolyzate).
    [33] Nutritional compositions according to the use of the invention may be prepared according to conventional practice. Suitable compositions are known as nutritional formulas for individuals suffering from food allergies, such as for milk proteins or soy allergies. Typically, the components of the nutritional composition can be mixed in dry form and then reconstituted in water, for example under stirring and / or heating.
    [34] Thus, any suitable protein source can be used for the preparation of the protein hydrolysates according to the invention. Preferably, the protein source is a high quality protein source; For example, milk protein, whey protein, casein protein, soy protein, meat-, fish- or poultry protein, or mixtures thereof may also be used.
    [35] More preferably, as an embodiment of the invention, the protein hydrolyzate is milk protein-hydrolysate.
    [36] Preferably, the protein hydrolyzate is whey protein hydrolyzate.
    [37] Protein hydrolysates can be prepared by any kind of hydrolysis. Preferably, it is prepared by acid or enzymatic hydrolysis. Patent EP 322589 (SOCIETE DES PRODUITS NESTLE) discloses a process suitable for obtaining protein hydrolysates within the meaning of the present invention. WO 9913738 (SOCIETE DES PRODUITS NESTLE) also discloses a process for obtaining particularly useful hydrolysates. In Example 1, the process protocol and analysis of the resulting hydrolyzate are described under the subtitle "Hydrolyte 3" of the above reference.
    [38] Preferably, as an embodiment of the invention, the degree of hydrolysis (DH) of the protein hydrolyzate is greater than 10%. Preferably, the degree of hydrolysis is greater than 20%, more preferably greater than 30%.
    [39] Preferably, in one embodiment, the degree of hydrolysis of the protein hydrolyzate is 10% to 70%. More preferably, it is 20% to 50%, more preferably 25% to 35%. For example, the degree of hydrolysis of the protein is 30%. When using whey protein hydrolyzate, a degree of hydrolysis of 30% means that the major part of the protein material is in dipeptid form. However, there may also be fewer tri-, oligo- and polypeptides and free amino acids with respect to the number of molecules.
    [40] Protein hydrolysates according to the invention can also be purchased commercially. For example, whey protein hydrolysate Lacprodan DI-3065 (Arla Food Ingredients Ltd) can be used.
    [41] Preferably, the protein hydrolyzate is the only source of protein of the nutritional composition.
    [42] The protein source preferably provides about 1-50% of the total caloric value of the nutritional composition. More preferably, it provides 10-30% of the total caloric value of the composition.
    [43] The nutritional composition may also contain a lipid source. The amount of fat or oil component can be adjusted according to situational factors such as the condition of the patient and the presence of other diseases. The fat source provides 0 to about 50% of the total caloric value of the composition.
    [44] Preferably it is present in an amount of 20 to 35% of the total caloric value. The fat component may be any lipid or fat known in the art to be suitable for use in nutritional compositions. Common fats include milk fat, sunflower oil, canola oil, egg yolk lipids, olive oil, cottonseed oil, coconut oil, hazelnut oil, palm oil, palm hull oil and / or rapeseed oil. The fat source may comprise a sufficient amount of long- and short-chain triglycerides (SCT, LCT and / or MCT). Lipids may be composed of saturated, unsaturated, mono-, di-, tri- or polyunsaturated fatty acids. Unsaturated fatty acids may be n-3 or n-6 fatty acids.
    [45] The nutritional composition may also contain a carbohydrate source. Carbohydrate components can provide 5 to 90% of the total caloric value. Preferably it contains 20 to 55%, more preferably 40 to 50% of the energy. The carbohydrate source can be any suitable carbohydrate or carbohydrate mixture. For example, the carbohydrate may be lactose, maltodextrin, modified starch, amylose starch, high amylose starch, topioka starch, corn starch, sucrose, galactose, glucose, fructose, or mixtures thereof. Thus, any poly-, oligo-, di- and / or monosaccharides known to be suitable for use in nutritional formulations may be added.
    [46] In addition, the nutritional composition may contain dietary fiber. Any suitable source of fiber may be used depending on the situational needs of the patient. Thus, soluble and insoluble fibers can be used alone or in combination. Soluble fibers may be viscous fibers or non-viscous fibers or combinations thereof. Possible sources of soluble fibers are guar rubber, xanthan rubber, gum arabic, pectin, β-glucan, inulin or mixtures thereof. Suitable sources of insoluble fibers include shell fibers derived from legumes and grains; For example, soybean hull fiber, oat husk fiber, barley hull fiber and soybean hull fiber. However, any suitable source of insoluble dietary fiber may be used.
    [47] The nutritional composition preferably comprises a full vitamin and mineral profile. For example, sufficient vitamins and minerals may be provided to supply about 75 to about 250% of the recommended daily allowable amount of vitamins and minerals per 1000 calories of the nutritional composition.
    [48] Various flavors, sweeteners and other additives may be present. For example, emulsifiers can be used.
    [49] If appropriate, the nutritional formula may also contain functional ingredients. Depending on the condition of the patient, suitable plant extracts can be added. For example, plant extracts known to have beneficial effects on gut flora, constipation, diarrhea and the like can be added. Examples are fennel, verbain, green tea, mint extract, probiotic fiber, chamomile, linden.
    [50] Nutritional compositions typically range from about 180 m0sm / l to about 400 m0sm / l; For example, an osmolality of about 250 mOsml / l to about 300 mOsm / l.
    [51] The energy density of the nutritional composition is preferably from about 500 kcal / l to about 1500 kcal / l; More preferably about 700 to about 1100 kcal / l.
    [52] The nutritional composition is preferably in a form in which the formulation can be used immediately. In this form, the composition can be supplied to the patient through the nasogastric, plant ducts or by the patient to drink. As such, the nutritional composition can be in various forms; For example, it may be a liquid infant formula, a fruit juice beverage, a milkshake beverage, or the like. However, the nutritional composition may be in the form of a soluble powder that can be reconstituted prior to use.
    [53] With regard to a method for the prevention or treatment of bacterial overgrowth or a method for the prevention or treatment of diseases related to the above according to the invention, the protein hydrolyzate is preferably the only source of proteinaceous material. In one embodiment, the proteinaceous material of a standard nutritional formula or food is partially or fully replaced with a protein as defined herein.
    [54] Nutritional compositions according to standard practice; For example, protein sources, carbohydrate sources, and lipid sources can be combined together to produce them. If used, emulsifiers may be included in the formulation. Vitamins and minerals may be added at this point, but are typically added later to avoid pyrolysis. Any lipophilic vitamin, emulsifier, or the like can be dissolved in the lipid source prior to compounding. The water, preferably reverse osmosis water, may then be mixed to form a liquid mixture. The temperature of the water may conveniently be from about 50 ° C. to about 80 ° C. to aid in the dispersion of the components. Commercial liquefaction agents can be used to form the liquid.
    [55] The liquid mixture may then be heat treated to reduce the bacterial load. For example, the liquid mixture may be rapidly heated to a temperature in the range of 75 ° C. to about 110 ° C. for about 5 seconds to about 5 minutes. This may be by steam injection or by a heat exchanger; For example with a plate heat exchanger.
    [56] The liquid mixture is then cooled to about 60 ° C. to about 85 ° C .; For example, it can be cooled by flash cooling. The liquid mixture is then homogenized in two steps, for example about 7 MPa in the first step and about 2 MPa to about 14 MPa in the second step. The homogenization mixture is then further cooled to any thermosensitive component; For example, vitamins and minerals can be added. The pH and solids content of the homogenization mixture is normalized at this point for convenience.
    [57] For products in liquid form, the homogenization mixture is preferably aseptically filled in a suitable container. Aseptic filling of the vessel may be accomplished by preheating the homogenization mixture (eg, at about 75 ° C. to 85 ° C.), and then injecting steam into the homogenization mixture to raise the temperature to about 120 to 180 ° C .; More preferably, it can be carried out by raising the temperature to about 140 to 160 ℃. The homogenization mixture may then be cooled to about 75-85 ° C. with flash cooling. The homogenization mixture can then be further homogenized, cooled to approximately room temperature and filled into the vessel. Suitable devices for carrying out aseptic filling of this nature are commercially available.
    [58] For products in powder form, the homogenization mixture is in powder; For example by spray drying. Conventional procedures may be used.
    [59] The nutritional composition can be used as a complete or supplemental nutrient for patients suffering from intestinal bacterial overgrowth, bacterial metastasis, sepsis and reduced availability of nutrients. This diagnosis is often made in premature or late babies, infants, critically ill and elderly people. Moreover, the nutritional composition can be used as a complete or supplemental nutrient for the prevention or treatment of intestinal bacterial overgrowth, bacterial metastasis, sepsis and reduced availability of nutrients in premature or periodic infants, infants, critically ill and elderly.
    [60] Without being bound by theory, the beneficial effects of protein hydrolysates on bacterial overgrowth are presumed to be related to high digestibility and rapid uptake of protein hydrolysates. The fact that most of the proteinaceous material is present in small fractions such as di-, tri- or tetrapeptides leads to the conclusion that they are completely absorbed in the small intestine even in patients with impaired gastrointestinal function. If such patient or premature infant consumes free protein, it will not be absorbed completely in the small intestine and will reach the lower extremity of the ileum. Proteinaceous material can serve as a substrate for bacteria that normally do not form colonies in this region of the digestive tract of healthy individuals. Thus, it has been found that bacterial overgrowth can increase the digestibility of proteinaceous substances and, more specifically, to prevent and treat by providing protein hydrolysates to diseased individuals rather than intact proteins. On the other hand, this explanatory model has not been proven to fully explain the surprising effects reported herein.
    [61] The following examples are given for illustrative purposes only and should never be considered as limiting the subject matter of the present application. % And parts are by weight unless otherwise indicated.
    [62] In the examples, a rat model was used, which does not reflect the same situation found in humans, and therefore the result is not directly and clearly applicable to humans. However, models were selected based on scientific studies recognizing the rat model to study the effects on nutritional interventions on the immune digestive system, such as premature infants, newborns as well as patients with digestive problems.
    [63] Example: Influence of Protein Sources (Free vs. Hydrolyzed Whey Protein) on Intestinal Bacterial Patterns in Artificially Raised Lactating Rats
    [64] Way
    [65] Animals and Diet
    [66] Sprague-Dawley rats were used in this study. Breeding mothers (obtained from Charles River Laboratories, Wilmington, Mass.) Were housed individually in plastic cages and reared under 12-h dark / light cycles at 21 ± 1 ° C. Animals were allowed free access to 7002Teklad 6% mouse / rat diet (Harlan Teklad, Madison, Wis.) And tap water. After 4 days of age, 18 suckling rats were divided into two experimental groups, and then a gastric fistula was installed and artificially reared for 10 days. Ten identical litters were used as parental controls.
    [67] Diet
    [68] Animals were fed two experimental milk formulations, having the same composition but different in protein source (Table 1): 100% Whey Protein (DH 0%) and 100% Extensive Whey Protein Hydrolysate (DH 30%). The molecular weight distribution of the protein hydrolyzate is shown in FIG. 1.
    [69] Composition of Experimental Formulas Used During Artificial ParentingDH0DH30 protein DH0 1 8.3g DH30 2 10.0 g Fat palm oil 2.59g 2.59g Coconut oil 2.16 g 2.16 g Soybean oil 1.73 g 1.73 g MCT Oil 1.29 g 1.29 g Corn oil 0.87 g 0.87 g cholesterol 25mg 25mg Lexitine (Topcitin) 0.33 g 0.33 g carbohydrate Lactose (Protein-Lactose) 2.2 g (0.33 g) 2.3 g (0.25 g) vitamin Teklad Vitamin Mixture # 40060 3 0.33 g 0.33 g Supplements Vitamin 4 50 mg 50 mg mineral 1N NaOH 3.33ml 1N KOH 1.67 ml Ca (lactate) 2 0.258 g Na2HPO4 0.167 g Calcium Glycerol Phosphate 1.02 g 1.02 g MgSO4 83mg 83mg CaCl2 55 mg CuSO4 solution (30mg / ml) 0.05ml 0.05ml FeSO4 solution (30mg / ml) 0.083ml 0.083ml ZnSO4 solution (38mg / ml) 0.117ml 0.117ml MnSO4 solution (10mg / ml) 0.006ml 0.006ml NaF solution (10mg / ml) 0.013ml 0.013ml KI solution (10mg / ml) 0.015ml 0.015ml Distilled water91.3ml 91.3ml Protein (g / 100ml)6.7 6.7 Fat (g / 100ml)9.2 9.2 Carbohydrate (g / 100ml)2.5 2.5 Energy content (Kj / 100ml)494 4941 DHO = Free Whey Protein (Globulal 80, Meggle, CH)2 DH30 = complete whey protein hydrolyzate (FIG. 1)3 Harlon Teklad, Madison, WI, USA4 riboflavin (16.7 g / Kg), niacin (26.0 g / Kg), pyridoxal (13.9 g / Kg), inositol (929.4 g / Kg), and sodium ascorbate salt (14.0 g / Kg)
    [70] Experimental protocol
    [71] All procedures used in this protocol have been reviewed and approved by the University of Arizona Animal Care Committee. Four-day-old suckling rats were anesthetized and gastroesophageal installed with a gallic-shaped polyethylene cannula (PE-20, Clay Adams / Benton Dickinson and Co., Parsippany, NJ). After postoperative recovery (including fasting for 2 hours), the pups were weighed and the volume of artificial formula given to each animal was calculated to deliver about 35-37% of body weight per 24 hours. The pups were placed in plastic cups and suspended in a 39 ° C. water bath during the parenting study to maintain ambient temperature and humidity. The gastric tube was connected to a syringe on a Model 44 Harvard Infusion Pump (Harvard Apparatus, South Natick., MA) in a refrigerator using Silastic tubing (Dow Coming Corp., Midland, Ml). The pump was set to stop for 40 minutes after delivering a 20 minute calorie diet every hour. The volume of diet delivered was recalculated daily. Daily weight, eyelids and tail length were recorded. Twice a day, the genital part was gently stimulated to induce urination and defecation.
    [72] On day 14, the pups were singled out and sacrificed. The gastrointestinal tract was rapidly removed under sterile conditions and excised into the duodenum (1 cm in the small intestine gastrointestinal tract), jejunum, ileum (half-proximal and distant parts of the remaining small intestine, respectively) and cecum. The plant and ileum were washed with 1 ml sterile ice cold 0.9% NaCl, 10% glycerol solution, respectively. The contents were collected directly and weighed in a NUNC (Nalgene) sterile tube. The caecum was opened, the contents removed with sterile spatula, weighed in a NUNC tube, and 1 ml of NaCl + glycerol solution was added thereto. The intestinal contents were immediately frozen in liquid nitrogen.
    [73] Analyzes of intestinal contents
    [74] Fungi in the jejunum, ileum and caecum contents (Bifidobacteria, Lactobacillus, Enterococcus, Enterobacteria and Clostridium perfringens) were evaluated by plating on selective or semiselective media.
    [75] 100-fold serial dilution was performed from -2 to -8 in Ringer's solution containing 0.5% cysteine. Petri dishes of various selection media were inoculated and incubated (see Table 2).
    [76] Culture condition of specific strain bacteria badge T (℃) Hours (h) Waiting Enterobacteria Drigalski (Sanofi Diagnostics Pasteur, France) 37 24 Aerobic Bifidobacteria Eugon Tomato * 37 48 Anaerobic Lactobacillus MRS (Difco, MI. USA) + Antibiotics ** 37 48 Anaerobic Cl. Perfringence NN baby *** 37 48 Anaerobic Enterococcus Azid Agar (Difco) 37 24 Aerobic *: Wadsworth Anaerobic Bacteriology Manual, V. Suter, D. Citron and S. Finegold Third ed. **: Phosphomycine (79.5mg / l) + Sulfarnethoxazole (0.93mg / l) + Trimethoprime (5mg / l) ***: NN Baby (Lowbury and Lilly, 1995).
    [77] Anaerocult A (MERCK, Darmstadt, Germany) was used to obtain an anaerobic atmosphere. After incubation, colonies were counted and further identified as needed. Lactobacillus and Bifidobacteria strains were identified by microscopy and enzymatic activity. The counts are expressed in cfu / g of fresh powdery sample (limit limit of 3.30 cfu / g) and log.
    [78] Statistical analysis
    [79] Due to nulle variability observed in some groups, traditional analyzes of ANOVA could not be performed. Instead, Wilcoxon rank test on group pairs was used. Mean differences with p values less than 0.05 were considered significant.
    [80] result
    [81] 2-4 show the clusters of enterobacteria, enterococcus and Lactobacillus in the contents of different long fragments.
    [82] Enterobacterial counts in the ileum were higher in DHO than in the other groups.
    [83] DH30 and MF were similar values at detection limits. In the cecum, the only unique group was MF, with a smaller number.
    [84] Enterococcus was much richer in plants and ileum with DH0 than with DH30 or MF. No significant difference in the diet was observed in the cecum.
    [85] Intestinal Lactobacillus was more abundant in DH0 than in other groups. Although in this case MF showed a value located between DHO and DH30, a similar trend was found in the plant. On the other hand, no difference was detected in the cecum.
    [86] Bifidobacteria were not detected in groups or intestinal fragments. In relation to Clostridium, only 4 animals (2 in DHO and 2 in MF) had detectable values in the cecum and only 1 in the ileum (in DHO). These values are negligible and no statistical comparison was made between diets.
    [87] conclusion
    [88] Rearing by free whey protein promoted bacterial overgrowth in the small intestine. This overgrowth was prevented to a significant extent by supplying complete whey protein hydrolysate, which resulted in a pattern of germs somewhat similar to that observed after parenting.
    [89] Thus, protein hydrolysates are useful means for the prevention or treatment of bacterial overgrowth and associated diseases. It is possible to restore intestinal fungal patterns similar to those of breastfed individuals.
    [90] It should be understood that various modifications and variations to the presently preferred embodiments described herein will be apparent to those skilled in the art. Such modifications and variations can be made without departing from the spirit and scope of the invention and without diminishing its accompanying advantages. Accordingly, such modifications and variations are intended to be included within the scope of the appended claims.
    权利要求:
    Claims (10)
    [1" claim-type="Currently amended] Use of protein hydrolysates for the preparation of nutritional compositions for the prophylaxis or treatment of bacterial overgrowth, necrotizing colitis, bacterial metastasis sepsis and / or reduced availability of nutrients.
    [2" claim-type="Currently amended] Use of protein hydrolysates for the preparation of nutritional compositions for the construction or promotion of balanced and / or beneficial flora patterns.
    [3" claim-type="Currently amended] Use according to claim 1 or 2, wherein the protein hydrolyzate is milk protein hydrolyzate.
    [4" claim-type="Currently amended] 4. Use according to any one of claims 1 to 3, wherein the protein hydrolyzate is whey protein hydrolyzate.
    [5" claim-type="Currently amended] The use according to any one of claims 1 to 4, wherein the nutritional composition is for premature infants or infants with infants, infants, critically ill or elderly.
    [6" claim-type="Currently amended] 6. Use according to any one of the preceding claims, wherein the nutritional composition is for pets.
    [7" claim-type="Currently amended] 7. Use according to any one of claims 1 to 6, wherein the degree of hydrolysis of the protein hydrolyzate is greater than 10%.
    [8" claim-type="Currently amended] 8. Use according to any one of claims 1 to 7, wherein the degree of hydrolysis of the protein hydrolyzate is 10% to 70%.
    [9" claim-type="Currently amended] A method of preventing or treating bacterial overgrowth or bacterial transfer, comprising administering a nutritional composition containing a protein hydrolyzate.
    [10" claim-type="Currently amended] A method of preventing or treating necrotic colitis, sepsis and / or reduced availability of nutrients, comprising administering a nutritional composition containing a protein hydrolyzate.
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    同族专利:
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    CN1536967A|2004-10-13|
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    US7666830B2|2010-02-23|
    AT354293T|2007-03-15|
    MXPA04000869A|2004-05-21|
    EP1414316A1|2004-05-06|
    DE60218318D1|2007-04-05|
    ZA200401607B|2005-03-10|
    JP4383165B2|2009-12-16|
    WO2003011055A1|2003-02-13|
    NO20040361L|2004-01-27|
    DE60218318T2|2007-11-15|
    BRPI0211485B1|2018-09-11|
    IL159396A|2006-09-05|
    EP1414316B1|2007-02-21|
    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    法律状态:
    2001-07-30|Priority to EP01118231.8
    2001-07-30|Priority to EP01118231A
    2002-07-25|Application filed by 소시에떼 데 프로듀이 네슬레 소시에떼아노님
    2002-07-25|Priority to PCT/EP2002/008336
    2004-03-04|Publication of KR20040019092A
    2007-11-20|First worldwide family litigation filed
    优先权:
    申请号 | 申请日 | 专利标题
    EP01118231.8|2001-07-30|
    EP01118231A|EP1281325A1|2001-07-30|2001-07-30|Nutritional composition preventing bacterial overgrowth|
    PCT/EP2002/008336|WO2003011055A1|2001-07-30|2002-07-25|Nutritional composition preventing bacterial overgrowth|
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