Chemistry: natural resins or derivatives; peptides or proteins; – Peptides of 3 to 100 amino acid residues – Tripeptides – e.g. – tripeptide thyroliberin – etc.
Reexamination Certificate
2000-03-15
2002-06-25
Low, Christopher S. F. (Department: 1653)
Chemistry: natural resins or derivatives; peptides or proteins;
Peptides of 3 to 100 amino acid residues
Tripeptides, e.g., tripeptide thyroliberin , etc.
C514S018700
Reexamination Certificate
active
06410685
ABSTRACT:
FIELD OF ART
This invention relates to an anti-stress agent and functional food having effects of preventing and mitigating mental and physical symptoms caused by stress.
BACKGROUND ART
In the modern society, people undergoes various kinds of stress caused by highly advanced and complicated scientific technology, or drastically changing social circumstances. Particularly, in the internationalized society, complex human relationships are formed, causing mental stress. It has been reported that a variety of symptoms are caused by mental stress.
It is recognized that mental stress has a great influence on circulatory system and immune system. However, the scientific concept and definition of stress have not yet been well established, so that means of evaluation of stress still have many problems, combined with methodological difficulties. However, in the recent years, studies of stress have been made from the medical point of view.
For example, it is reported that when one undergoes stress, angiotensin II increases, and intracorporeal sodium due to sodium reabsorbancy becomes excess, which causes rise in blood pressure (Osamu Mobara et al.: Taisha, 28, 2, 323, 1991). Based on such findings, studies have been made on the effect of enalapril and alacepril, which are angiotensin converting enzyme inhibitors and used as antihypertensive agents, on hypertension caused by stress (The American Journal of Cardiology; 68, 15, 1362(1991), Internal Medicine; 32, 9, 691(1993)). However, it is considered that suffering stress not only causes rise in blood pressure, but also influences various factors to cause stomach ulcer, ischemic heart diseases, cerebrovascular diseases, hyperlipemia, or the like. Therefore, though stress is regarded as one of the causes of hypertension, it is not believed that the anti-stress effect is achieved merely by suppressing the rise in blood pressure.
As an agent for preventing and mitigating mental and physical symptoms caused by stress, chemically synthesized medicaments such as a tranquilizer, an antianxiety agent, and sleeping pills are presently used. However, these medicaments have habituation and side effect problems, so that it is not preferable to use them daily for the purpose of preventing mental and physical symptoms caused by stress. Accordingly, an anti-stress agent that can be taken repeatedly and daily without any problems with safety, and that can mitigate and prevent mental and physical symptoms caused by stress are desired and are under development. For example, there are proposals such as an anti-stress agent containing as an effective ingredient L-theanine contained in tea leaves (Japanese Laid-open Patent Application No. 6-100442), an anti-stress composition containing imidazole compounds such as anserine, valenine, n-methylhistidine, or r-methylhistidine (Japanese Laid-open Patent Application No. 9-20660), and anti-stress food containing a composition of glutathione and antioxidant (Japanese Laid-open Patent Application No. 8-275752). There is also a report on stress reducing effect of fragrance (Fragrance Journal: 1991-11, p44-49). However, there has not been reported that a tripeptide has the effect of mitigating and preventing mental and physical symptoms caused by stress.
DISCLOSURE OF THE INVENTION
It is an object of the present invention to provide an anti-stress agent and functional food which can fulfill the social demand as mentioned above, which can be taken repeatedly and daily without any problems with safety, and which can mitigate and prevent mental and physical symptoms caused by stress.
According to the present invention, there is provided an anti-stress agent comprising as an effective ingredient a tripeptide and/or a salt thereof having angiotensin converting enzyme inhibitory activity.
According to the present invention, there is also provided the anti-stress agent wherein said tripeptide is Ile-Pro-Pro and/or Val-Pro-Pro.
According to the present invention, there is further provided use of the tripeptide and/or the salt thereof for the manufacture of an anti-stress agent.
According to the present invention, there is also provided food having an anti-stress effect and comprising said anti-stress agent.
According to the present invention, there is further provided use of the tripeptide and/or the salt thereof for the manufacture of food having an anti-stress effect.
According to the present invention, there is further provided a method for producing the food having anti-stress effect comprising fermenting a medium containing a peptide and/or a protein including a sequence Ile-Pro-Pro and/or Val-Pro-Pro with lactic acid bacteria under conditions for a tripeptide Ile-Pro-Pro and/or Val-Pro-Pro to be produced in a resulting fermented medium.
According to the present invention, there is also provided a method for reducing stress comprising orally administering an effective amount of a tripeptide and/or a salt thereof having angiotensin-converting enzyme inhibitory activity.
PREFERRED EMBODIMENTS OF THE INVENTION
The anti-stress agent of the present invention contains, as an effective ingredient, a tripeptide and/or a salt thereof having angiotensin converting enzyme inhibitory activity. In the present invention, “anti-stress” effect means an activity to cause approximation of the conditions of a subject to the conditions without stress, e.g., an activity to reduce systolic and diastolic blood pressures which have been increased due to stress, and an activity to inhibit or prevent lowering in immunological function caused by stress, such as lowering in spleen cell response.
The tripeptide may be preferably selected from the group consisting of Ile-Pro-Pro, Val-Pro-Pro (abbreviated hereinbelow as IPP and VPP, respectively) and mixtures thereof that have angiotensin converting enzyme inhibitory activity.
The salt of the tripeptide may include pharmacologically acceptable salts, such as inorganic salts such as hydrochloride, sulfate and phosphate, and organic salts such as citrate, maleate, fumarate, tartrate and lactate.
The tripeptide may be produced by, e.g., fermentation with microorganism, enzyme hydrolysis, or chemical synthesis.
The fermentation with microorganism can be performed by culturing lactic acid bacteria in a medium of a food material containing a peptide and/or a protein including an amino acid sequence corresponding to the tripeptide, such as sequences Ile-Pro-Pro and/or Val-Pro-Pro.
The medium is preferably a food material containing a peptide and/or a protein including an amino acid sequence corresponding to the tripeptides. The food material may be milk, milk casein, corn, corn protein, wheat, wheat protein, soybean, de-fat soybean or soybean protein. The medium may further contain other ingredients such as yeast extract, vitamins and minerals, if necessary.
As the lactic acid bacteria, lactic acid bacteria of the genus Lactobacillus may be employed. For example,
Lactobacillus helveticus, Lactobacillus delbruekii
subsp.
bulgaricus, Lactobacillus acidophilus, Lactobacillus fermentum
or
Lactobacillus casei
subsp.
casei
maybe employed. Specifically,
Lactobacillus helveticus
ATCC55796
, Lactobacillus delbruekii
subsp.
bulgaricus
ATCC11842
, Lactobacillus acidophilus
ATCC4356
, Lactobacillus fermentum
ATCC14931 or
Lactobacillus casei
subsp.
casei
ATCC393 may be employed.
The fermentation may be performed by heat-sterilizing the medium, cooling the medium to a desired culturing temperature, and then inoculating the medium with a pre-cultured lactic acid bacteria starter. The inoculation amount of the lactic acid bacteria starter is preferably 10
5
to 10
7
cells of the lactic acid bacteria per 1 g of the medium. The culture temperature may be 20 to 50° C., and preferably 30 to 45° C. The culturing time maybe 3 to 48 hours, and preferably 6 to 24 hours. The culturing may be terminated when number of cells of the lactic acid bacteria reaches 10
8
cells/g or more and acidity of the lactic acid reaches 1 or more. The resulting cultured medium usually contains 0.1 to 100 &mgr;g/g of IPP and/or VPP,
Masuyama Akihiro
Takano Toshiaki
Calpis Co., Ltd.
Darby & Darby
Low Christopher S. F.
Lukton David
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