Title:  Methods of preventing or treating allergies

United States Patent:  6,506,380

Issued:  January 14, 2003

Inventors:  Isolauri; Erika (Raisio, FI); Metsaniitty; Leena (Helsinki, FI); Korhonen; Hannu (Riihimaki, FI); Salminen; Seppo (Turku, FI); Syvaoja; Eeva-Liisa (Espoo, FI)

Assignee:  Valio Oy (Helsinki, FI)

Appl. No.:  973963

Filed:  May 29, 1998

PCT Filed:  January 3, 1997

PCT NO:  PCT/FI96/00350

371 Date:  June 12, 1996

The present invention provides method of making a protein hydrolysate formula and protein hydrolysate formulas made thereby for downregulating hypersensitivity and for promoting gut immune barrier, and methods of preventing or treating allergies, especially cow's milk allergy by combining the protein with probiotic gastrointestinal bacteria, especially Lactobacilli. The probiotics make it possible to influence the immunological balance, whereby allergy can be prevented by affecting the initiation mechanism of allergy. The present invention makes it possible to develop a person's tolerance of proteins by actively promoting a tolerogenic immune response. In addition, present invention provides for administering fragments of an allergen modified by probiotic gastrointestinal bacteria in order to desensitize a immune response to systemic hyporesponsiveness.

SUMMARY OF THE INVENTION

The present inventors have now found that certain bacteria of the gastrointestinal tract, especially Lactobacilli, and especially bacteria having probiotic characteristics, can be used to enhance the efficacy of elimination diets and to improve the oral tolerance, in preventing or treating food-induced hypersensitivity reactions in a patient.

One aspect of the invention is that protein hydrolysates obtained by hydrolysis of proteins with above mentioned gastrointestinal bacteria can also be used to said purpose. We show here that protein hydrolysates obtained according to this invention have an immunological effect promoting hypoallergenicity. The hydrolysates downregulate hypersensitivity reactions thus promoting the gut immune barrier function, i.e. stabilising the gut mucosal barrier.

The present invention provides an improved protein hydrolysate formula downregulating hypersensitivity reactions and promoting the gut immune barrier function. The hydrolysate formula is obtainable by hydrolysing proteins with enzymes obtained from probiotic gastrointestinal bacteria, especially Lactobacilli, which have adhesive and colonizing characteristics and a protease enzyme system which are similar to those of the strain Lactobacillus GG (ATCC 53103), and with trypsin and/or pepsin.

Alternatively, a protein hydrolysate formula of the invention can be obtained by hydrolysing proteins with trypsin and/or pepsin, and adding to the hydrolysate so obtained a bacterial preparation comprising probiotic gastrointestinal bacteria, especially Lactobacilli, which have adhesive and colonizing characteristics and a protease enzyme system which are similar to those of the strain Lactobacillus GG (ATCC 53103). The bacteria are added into the hydrolysate formula preferably as a lyophilized preparation.

While administering such a hydrolysate formula to a patient, it is to be expected that the hydrolysing enzymes of the bacteria present are released in vivo whereby the same effect is achieved as with an improved hydrolysate formula as defined above. In addition, the viable bacteria stabilize the gut mucosal barrier enhancing the local defence.

An embodiment of this invention is a method of preventing or treating food-induced hypersensitivity reactions in an infant, which method comprises the step of administering to an infant at risk the improved protein hydrolysate formula of the invention, or alternatively a protein hydrolysate formula together with a bacterial preparation comprising probiotic gastrointestinal bacteria, especially Lactobacilli, which have adhesive and colonizing characteristics and a protease enzyme system which are similar to those of the strain Lactobacillus GG (ATCC 53103).

A further embodiment of this invention is a method of treating cow's milk allergy in a patient, comprising administering to the patient the improved protein hydrolysate formula of the invention or, alternatively administering a protein hydrolysate formula together with a bacterial preparation comprising probiotic gastrointestinal bacteria, especially Lactobacilli, which have adhesive and colonizing characteristics and a protease enzyme system which are similar to those of the strain Lactobacillus GG (ATCC 53103).

The invention also provides a method of promoting tolerogenic immune responses to food antigens in a patient, comprising oral administration of the improved protein hydrolysate formula of the invention to the patient, or, alternatively, a bacterial preparation comprising probiotic gastrointestinal bacteria, especially Lactobacilli, which have adhesive and colonizing characteristics and a protease enzyme system which are similar to those of the strain Lactobacillus GG (ATCC 53103), or, alternatively, a protein hydrolysate formula together with a bacterial preparation comprising probiotic gastrointestinal bacteria, especially Lactobacilli, which have adhesive and colonizing characteristics and a protease enzyme system which are similar to those of the strain Lactobacillus GG (ATCC 53103).

In the methods of the invention as defined above, when a protein hydrolysate formula is used in combination with selected probiotic bacteria as defined above, such a formula can be any suitable protein hydrolysate formula, known or novel. It can thus be either a partial protein hydrolysate, or alternatively an extensively hydrolysed formula. Preparation of a protein hydrolysate suitable for this purpose is disclosed e.g. in EP patent application No. 601 802.

Preferred bacterium to be used in the formulae and methods of the invention is Lactobacillus GG (ATCC 53103).

In this specification and in the appended claims the phrase "bacteria, especially Lactobacilli, which have adhesive and colonizing characteristics and a protease enzyme system which are similar to those of the strain Lactobacillus GG (ATCC 53103)" should be understood to define bacteria whose adhesive and colonizing characteristics are comparable to those of the LGG strain, e.g. as defined in EP-patent 199 535. These bacteria are also supposed to have same kind of enzyme system as LGG, which means that enzymes derived from such bacteria are able to degrade proteins to produce hydrolysation products with same effects as those obtained using enzymes derived from LGG.

What is claimed is:

1. A method of making a hypoallergenic protein hydrolysate formula to be administered to a patient for downregulating hypersensitivity reactions and for promoting gut immune barrier in said patient, comprising:

hydrolysing proteins with enzymes obtained from a bacterial preparation comprising Lactobacillus GG (ATCC 53103) and with pepsin and/or trypsin,

wherein the protein hydrolysate formula has an immunological effect that promotes hypoallergenicity when administered to said patient.

 

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