HK1171379B - Composition for improving brain function and method for improving brain function - Google Patents

Description

Composition for improving brain function and method for improving brain function

Technical Field

The present invention relates to compositions and methods for improving brain function.

Background

The symptoms and diseases caused by brain hypofunction include depression, integration disorder, delirium, senile dementia (cerebrovascular senile dementia, Alzheimer disease, etc.), etc. With the advanced age of modern society, the increase of patients with senile dementia gradually becomes a bigger social problem. The symptoms of senile dementia vary from person to person, but commonly seen symptoms include memory impairment, disorientation, low judgment and thinking ability, and the like. In the case of senile dementia, the patients are often cerebrovascular senile dementia and Alzheimer's disease. For example, senile dementia of cerebrovascular type causes impairment of nerve cells in cerebral cortex and hippocampus due to cerebral blood flow disorder, resulting in cognitive and memory disorders. Therefore, a drug for improving cerebral blood flow or a drug for protecting cerebral nerve cells is applied to the treatment of basic diseases such as hypertension, diabetes, hypercholesterolemia, and the like, which may cause cerebrovascular disorders. On the other hand, the cause of Alzheimer's disease is unknown, but it has been confirmed that the level of acetylcholine, a neurotransmitter in the brain of a patient, is low, and therefore, it is considered that the low function of cholinergic nerves is one of the causes (for example, refer to Science,217,408-414 (1982)). Therefore, in alzheimer's disease, a treatment method aimed at increasing the concentration of acetylcholine and preventing the functional deterioration of cholinergic nerves has become the mainstream.

Currently, acetylcholinesterase inhibitors such as donepezil hydrochloride are marketed as therapeutic agents for alzheimer's disease. However, acetylcholinesterase inhibitors such as donepezil hydrochloride have a problem that they cannot be taken for a long period of time because of hepatotoxicity and strong side effects, and are expensive.

In addition, as a report showing an effect of improving amnesia, it has been reported that, for example, XPLPR (X is L, I, M, F, W) (seq id No. 17) administered intracerebroventricularly or orally at 300mg/kg shows an improvement effect on scopolamine-induced amnesia, and one of the mechanisms is release of acetylcholine mediated by a C3a receptor in the brain (japanese patent No. 3898389). Scopolamine has been used in the preparation of model animals for the development of therapeutic agents for alzheimer's disease because it causes a decrease in cholinergic nerve function as a muscarinic receptor antagonist and acts as a brain dysfunction-inducing agent. The effect of preventing and/or ameliorating brain dysfunction due to the action of scopolamine can be actually verified by behavioral pharmacological tests such as a Y-maze test, an eight-direction maze test, and a passive avoidance test. In addition, by performing the same behavioral pharmacological test using normal animals, the effect of improving and/or strengthening brain functions can be actually verified. However, all peptides require a large amount of administration such as oral administration, intraperitoneal administration, intracerebroventricular administration in order to exhibit their effects, and do not exhibit sufficient effects as substances that can be orally ingested. In addition, there is no report on the evaluation of the peptide of the present invention and its analogs, and the effect thereof on the improvement of brain function is not clear.

Therefore, as the aging society becomes more advanced, development of drugs which prevent symptoms and diseases caused by brain function deterioration and exhibit an improvement effect, and excellent and safe compounds to be applied to foods are required.

Disclosure of Invention

The present invention provides a composition for improving brain function, which is low in dose and can be orally ingested. In addition, the present invention provides methods of improving brain function.

(1) The present invention provides a composition for improving brain function, comprising X-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu-Y (wherein X is absent or represents any of Ile or Asn-Ile, and Y is absent or represents Val-Met) (SEQ ID NO:1 to 6) or a salt thereof as an active ingredient.

(2) The present invention relates to a composition for improving brain function, which comprises Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu (SEQ ID NO:1) or a salt thereof as an active ingredient.

(3) The present invention is a composition for improving brain function, which comprises Ile-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu (SEQ ID NO:2) or a salt thereof as an active ingredient.

(4) The present invention is a composition for improving brain function, comprising Asn-Ile-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu (SEQ ID NO:3) or a salt thereof as an active ingredient.

(5) The present invention is a composition for improving brain function, comprising Asn-Ile-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu-Val-Met (SEQ ID NO:6) or a salt thereof as an active ingredient.

(6) The present invention provides a composition for improving brain function, comprising X-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu-Y (wherein X is absent or represents any one of Thr-Gln-Thr-Pro, Pro-Leu-Thr-Gln-Thr-Pro, or Pro, and Y is absent or represents Val-Met) (SEQ ID NO: 7 to 16) or a salt thereof as an active ingredient.

(7) The present invention is a composition for improving brain function, which comprises Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu (SEQ ID NO: 7) or a salt thereof as an active ingredient.

(8) The present invention is a composition for improving brain function, comprising Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu (SEQ ID NO: 8) or a salt thereof as an active ingredient.

(9) The present invention is a composition for improving brain function, comprising Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu (SEQ ID NO:9) or a salt thereof as an active ingredient.

(10) The present invention is a composition for improving brain function, which comprises Pro-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu (SEQ ID NO: 10) or a salt thereof as an active ingredient.

(11) The present invention is a composition for improving brain function, which comprises Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu (SEQ ID NO: 11) or a salt thereof as an active ingredient.

(12) The composition of any one of (1) to (11) of the present invention is for oral ingestion.

(13) In particular, the present invention is the composition according to any one of (1) to (12), wherein the improvement in brain function is prevention of amnesia or enhancement of memory.

(14) The present invention is a method for improving brain function, comprising the step of administering X-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu-Y (wherein X is absent or represents any of Ile or Asn-Ile, and Y is absent or represents Val-Met) or a salt thereof to a non-human animal.

(15) The present invention is a method for improving brain function, comprising the step of administering Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu or a salt thereof to a non-human animal.

(16) The present invention is a method for improving brain function, comprising the step of administering Ile-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu or a salt thereof, particularly to a non-human animal.

(17) The present invention is a method for improving brain function, comprising the step of administering Asn-Ile-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu or a salt thereof to a non-human animal.

(18) The present invention is a method for improving brain function, comprising the step of administering Asn-Ile-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu-Val-Met or a salt thereof to a non-human animal.

(19) The present invention is a method for improving brain function, comprising the step of administering X-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu-Y (wherein X is absent or represents any of Thr-Gln-Thr-Pro, Pro-Leu-Thr-Gln-Thr-Pro, Leu-Thr-Gln-Thr-Pro or Pro, and Y is absent or represents Val-M et) or a salt thereof.

(20) The present invention is a method for improving brain function, comprising the step of administering Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu or a salt thereof to a non-human animal.

(21) The present invention is a method for improving brain function, comprising the step of administering Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu or a salt thereof to a non-human animal.

(22) The present invention is a method for improving brain function, comprising the step of administering Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu or a salt thereof to a non-human animal.

(23) The present invention is a method for improving brain function, comprising the step of administering Pro-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu or a salt thereof to a non-human animal.

(24) The present invention is a method for improving brain function, comprising the step of administering Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu or a salt thereof to a non-human animal.

(25) The present invention is the method according to any one of (14) to (24), wherein the administration is oral administration.

(26) Specifically, the present invention is the method according to any one of (14) to (25), wherein the improvement in brain function is prevention of amnesia or enhancement of memory.

Drawings

FIG. 1 shows the effect of the peptide Asn-Ile-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu (NIPPLTQTPVVVPFLQPE) in preventing scopolamine-induced amnesia. The effect of preventing amnesia was evaluated by the method described in example 1 for each of mice administered with water (control), or scopolamine alone, or NIPPLTQTPVVVPPFLQPE 0.05.05 nmol/kg body weight or 0.5nmol/kg body weight or 1.5nmol/kg body weight or 5nmol/kg body weight or 50nmol/kg body weight or 500nmol/kg body weight together with scopolamine. The vertical axis of fig. 1 represents the rate of change of spontaneous alternating behavior. The graph shows the spontaneous alternation behavior change rates of the control group, the scopolamine control group, NIPPLTQTPVVVPPFLQPE 0.05.05 nmol/kg body weight, 0.5nmol/kg body weight, 1.5nmol/kg body weight, 5nmol/kg body weight, 50nmol/kg body weight, and 500nmol/kg body weight administration groups in this order from the left. To confirm whether or not amnesia was induced, a student's t-test was performed to examine the significance of the difference between the control group to which water was administered and the scopolamine-alone control group to which scopolamine was administered. Denotes P <0.01 compared to water administration control group. NIPPLTQTPVVVPPFLQPE significance test of differences between the group administered and the scopolamine control group was performed by means of a dannett-type multiple comparison test. # indicates P <0.01 compared to the scopolamine control group.

FIG. 2 shows the peptides Asn-Ile-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu (NIPPLTQTPVVVVPFLQPE), Asn-Ile-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu-Val-Met (NIPPLTQTPVVVVPFLFLEVM), Ile-Pro-Pro-Leu-Thr-Pro-Val-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu (IPPLTQVPPFQPE), Asn-Ile-Pro-Leu-Thr-Pro-Val-Val-Pro-Val Pro-Pro-Phe-Leu-Gln-Pro (NIPPLTQTPVVVPFLQP) for preventing scopolamine induced amnesia. The amnesia preventing effect was evaluated by the method described in example 2 using water (control), scopolamine alone, or NIPPLTQTPVVVPPFLQPE 50nmol/kg body weight, NIPPLTQTPVVVPPFLQPEVM 50nmol/kg body weight, IPPLTQTPVVVPPFLQPE 50nmol/kg body weight, or NIPPLTQTPVVVPPFLQP 50nmol/kg body weight, together with scopolamine to mice. The vertical axis of fig. 2 represents the rate of change of spontaneous alternating behavior. To confirm whether or not amnesia was induced, a student's t-test was performed to examine the significance of the difference between the control group to which water was administered and the scopolamine-alone control group to which scopolamine was administered. Denotes P <0.01 compared to water administration control group. The significance test of the differences between the peptide administration group and the scopolamine control group was performed by means of a dannett-type multiple comparison test. # indicates P <0.01 compared to the scopolamine control group.

FIG. 3 shows the effect of the peptides Asn-Ile-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu (NIPPLTQTPVVVPPPFLQPE), Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu-Val-Met (PPLTQTPVVVPFLQPE) on the prevention of scopolamine induced amnesia. The amnesia preventing effect was evaluated by the method described in example 3, respectively, by administering water (control), scopolamine alone, NIPPLTQTPVVVPPFLQPE 500nmol/kg body weight or PPLTQTPVVVPPFLQPE 500nmol/kg together with scopolamine to mice. The vertical axis of fig. 3 represents the rate of change in spontaneous alternation behavior. To confirm whether or not amnesia was induced, a student's t-test was performed to examine the significance of the difference between the control group to which water was administered and the scopolamine-alone control group to which scopolamine was administered. Denotes P <0.01 compared to water administration control group. The significance test of the differences between the peptide administration group and the scopolamine control group was performed by means of a dannett-type multiple comparison test. # denotes P <0.05 compared to the scopolamine control group.

FIG. 4 shows the memory enhancing effect of the peptide Asn-Ile-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu (NIPPLTQTPVVVPFLQPE). The effect of enhancing memory was evaluated by the method described in example 4, respectively, by administering water (control) or NIPPLTQTPVVVPPFLQPE 500nmol/kg to the mice. The vertical axis of fig. 4 represents the ratio of the search time. The significance of the difference between the control and peptide groups was tested by student's t-test for the proportion of time explored. Denotes P <0.05 compared to water administration control group.

FIG. 5 shows the effect of the peptide Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu (TQTPVVPPFLQPE) in the prevention of scopolamine induced amnesia. The amnesia preventing effect was evaluated by the method described in example 5, respectively, by administering water (control), scopolamine alone, or TQTPVVVPPFLQPE 50nmol/kg body weight together with scopolamine to mice. The vertical axis of fig. 5 represents the rate of change of spontaneous alternating behavior. To confirm whether or not amnesia was induced, a student's t-test was performed to examine the significance of the difference between the control group to which water was administered and the scopolamine-alone control group to which scopolamine was administered. P <0.01 compared to water administration control. The significance test of the differences between the TQTPVVVPPFLQPE-administered group and the scopolamine-controlled group was performed by student's t-test. # denotes P <0.05 compared to the scopolamine control group.

FIG. 6 shows the effect of the peptides Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu (PLTQTPVVVVPPFLQPE), Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu (LTQTPVPPFLQPE), Pro-Val-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu (PVVVPFLQPE), Val-Val-Pro-Phe-Leu-Gln-Pro-Glu (VVPLQPE) on the prevention of scopolamine induced amnesia. The amnesia preventing effect was evaluated by the method described in example 6, respectively, by administering water (control), scopolamine alone, or PLTQTPVVVPPFLQPE 500nmol/kg body weight, LTQTPVVVPPFLQPE 500nmol/kg body weight, PVVVPPFLQPE 500nmol/kg body weight, or VVVPPFLQPE 500nmol/kg body weight to mice together with scopolamine. The vertical axis of fig. 6 represents the rate of change of spontaneous alternating behavior. To confirm whether or not amnesia was induced, a student's t-test was performed to examine the significance of the difference between the control group to which water was administered and the scopolamine-alone control group to which scopolamine was administered. P <0.01 compared to water administration control. The significance of differences between each peptide-administered group and the scopolamine-controlled group was tested by student's t-test. # denotes P <0.05, as compared with scopolamine control group,Represents P < 0.1 compared with scopolamine control group.

Detailed Description

The composition of the present invention comprises a peptide X-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu-Y (wherein X is absent or represents either Ile or Asn-Ile, wherein Y is absent or represents Val-Met) or a peptide X-Val-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu-Y (wherein X is absent or represents either Thr-Gln-Thr-Pro, Pro-Leu-Thr-Gln-Thr-Pro, or Pro, wherein Y is absent or represents either Met-Val), In particular the peptide Asn-Ile-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu, or the peptide Asn-Ile-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu-Val-Met, or the peptide Ile-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu, or the peptide Pro-Pro-Leu-Thr-Pro-Val-Val-Pro-Phe-Leu-Pro-Val-Val-Pro -Gln-Pro-Glu, or peptide Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu, or peptide Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu, or a peptide Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu, or a peptide Pro-Val-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu, or a peptide Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu. A peptide X-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu-Y (wherein X is absent or represents either Ile or Asn-Ile, and Y is absent or represents Val-Met) or a peptide X-Val-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu-Y (wherein X is absent or represents either Thr-Gln-Thr-Pro, Pro-Leu-Thr-Gln-Thr-Pro, or Pro, and Y is absent or represents either Val-Met or Val-Met), In particular the peptide Asn-Ile-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu, or the peptide Asn-Ile-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu-Val-Met, or the peptide Ile-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu, or the peptide Pro-Pro-Leu-Thr-Pro-Val-Val-Pro-Phe-Leu-Pro-Val-Val-Pro the-Gln-Pro-Glu or peptide Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu, or the peptide Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu, or the peptide Pro-Val-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu, or the peptide Val-Val-Pro-Phe-Leu-Gln-Pro-Glu may be synthesized by organic chemistry The peptide of (4) may be a peptide derived from a natural product. As a method for synthesizing these peptides by organic chemistry, general methods such as a solid phase method (t-Boc method, Fmoc method) and a liquid phase method can be used, and for example, synthesis can be carried out using an automatic peptide synthesizer such as a peptide synthesizer (PSSM-8 type) manufactured by Shimadzu corporation. The reaction conditions for peptide synthesis and the like may be arbitrarily set according to the common technical knowledge of those skilled in the art, such as the selected synthesis method and appropriate reaction conditions. Methods for purifying chemically synthesized peptides are also well known to those skilled in the art.

In the present specification, the peptide X-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu-Y (wherein X does not exist or represents either Ile or Asn-Ile, and Y does not exist or represents Val-Met) or the peptide X-Val-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu-Y (wherein X does not exist or represents either Thr-Gln-Thr-Pro, Pro-Leu-Thr-Pro, Leu-Thr-Gln-Thr-Pro or Pro, and wherein Y does not exist or represents Val-Met), In particular the peptide Asn-Ile-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu, or the peptide Asn-Ile-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu-Val-Met, or the peptide Ile-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu, or the peptide Pro-Pro-Leu-Thr-Pro-Val-Val-Pro-Phe-Leu-Pro-Val-Val-Pro -Gln-Pro-Glu or peptide Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu, or peptide Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu, or peptide Pro-Val-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu, or peptide Val-Val-Val-Pro-Pro, except where specifically stated otherwise and where explicitly excluded from the context, "X-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu-Y (wherein X is absent or represents either Ile or Asn-Ile, and wherein Y is absent or represents Val-Met) or X-Val-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu-Y (wherein X is absent or represents either Thr-Gln-Thr-Pro, Pro-Leu-Thr-Gln-Thr-Pro, Leu-Thr-Gln-Thr-Pro or Pro, wherein Y is absent or represents Val-Met), particularly Asn-Ile-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu, or Asn-Ile-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu-Val-Met, or Ile-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu, or Pro-Leu-Thr-Gln-Pro-Val-Val- Pro-Pro-Phe-Leu-Gln-Pro-Glu, or Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu, or Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Phe-Leu-Pro-Glu, or Leu-Thr-Gln-Thr-Pro-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu, or Pro-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu, or Val-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu, and "peptide X-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu-Y (wherein X is absent or represents either Ile or Asn-Ile, wherein Y is absent or represents Val-Met) or a peptide X-Val-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu-Y (wherein X is absent or represents either Thr-Gln-Thr-Pro, Pro-Leu-Thr-Gln-Thr-Pro, Leu-Thr-Gln-Thr-Pro or Pro, wherein Y is absent or represents Val-Met), in particular a peptide Asn-Ile-Pro-Leu-Thr-Gln-Thr -Pro-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu, or peptide Asn-Ile-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu-Val-Met, or peptide Ile-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu, or peptide Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu or peptide Thr-Gln-Thr-Pro-Val-Val- Also included are salts of Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-G lu, or the peptide Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu, or the peptide Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu, or the peptide Pro-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu, or the peptide Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu. Such salts include, for example, sodium salts, potassium salts, hydrochloride salts, and the like which can exist under physiological conditions. In addition, in the composition of the present invention, in addition to the peptide X-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu-Y (wherein X does not exist or represents either Ile or Asn-Ile, and Y does not exist or represents Val-Met) or the peptide X-Val-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu-Y (wherein X does not exist or represents either Thr-Gln-Thr-Pro, Pro-Leu-Thr-Pro, Leu-Thr-Gln-Thr-Pro or Pro, wherein Y is absent or represents Val-Met), particularly the peptide Asn-Ile-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu, or the peptide Asn-Ile-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu-Val-Met, or the peptide Ile-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu, or the peptide Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val- Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu, or peptide Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu, or peptide Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu, or peptide Leu-Thr-Gln-Thr-Pro-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu, or peptide Val-Val-Pro-Pro-Phe-Leu- The peptide may contain a free amino acid or a salt thereof in addition to Pro-Glu. In addition, in the context of the present invention, the three letter and one letter representations of amino acids and the representation of peptides follow general rules well known to those skilled in the art.

The composition of the present invention or the peptide X-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu-Y (wherein X does not exist or represents either Ile or Asn-Ile, and Y does not exist or represents Val-Met) or the peptide X-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu-Y (wherein X does not exist or represents either Thr-Gln-Thr-Pro, Pro-Leu-Thr-Gln-Thr-Pro, or Pro, and wherein Y does not exist or represents Val-Met), In particular the peptide Asn-Ile-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu, or the peptide Asn-Ile-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu-Val-Met, or the peptide Ile-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu, or the peptide Pro-Pro-Leu-Thr-Pro-Val-Val-Pro-Phe-Leu-Pro-Val-Val-Pro The brain function improving effect of-Gln-Pro-Glu, or peptide Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu, or peptide Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu, or peptide Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu, or peptide Val-Val-Pro-Phe-Leu-Gln-Pro-Glu may be used in the case of improving the brain function of For example, the system based on the evaluation system of the therapeutic agent for Alzheimer's disease using the Y-shaped maze is confirmed. Specifically, a drug which induces amnesia by inducing a functional decline of cholinergic nerves and brain dysfunction by using a muscarinic receptor antagonist such as scopolamine is administered alone to a rat or a mouse, or the composition of the present invention or X-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu-Y (wherein X does not exist or represents any of Ile or Asn-Ile, and Y does not exist or represents Val-Met) or X-Val-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu-Y (wherein X does not exist or represents Thr-Gln-Thr-Pro, or X does not exist or represents Thr-Gln-Thr-Pro, Pro-Leu-Thr-Gln-Thr-Pro, Leu-Thr-Gln-Thr-Pro or Pro, wherein Y is absent or represents Val-Met), particularly Asn-Ile-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu, or Asn-Ile-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu-Val-Met, or Ile-Pro-Pro-Leu-Thr-Pro-Val-Val-Pro-Phe-Leu-Gln-Pro-Val-Val-Met, or Ile-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val- -Pro-Glu, or Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu, or Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu, or Pro-Val-Val-Pro-Phe-Leu-Gln- Pro-Glu, or Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu, administered simultaneously with or prior to the administration of the above-mentioned agents, or the composition of the invention or X-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu-Y (wherein X is absent or represents any of Ile or Asn-Ile, and Y is absent or represents Val-Met) or X-Val-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu-Y (wherein X is absent or represents Thr-Gln-Thr-Pro, or, Pro-Leu-Thr-Gln-Thr-Pro, Leu-Thr-Gln-Thr-Pro or Pro, wherein Y is absent or represents Val-Met), particularly Asn-Ile-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu, or Asn-Ile-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu-Val-Met, or Ile-Pro-Pro-Leu-Thr-Pro-Val-Val-Pro-Phe-Leu-Gln-Pro-Val-Val-Met, or Ile-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val- -Pro-Glu, or Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu, or Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu, or Pro-Val-Val-Pro-Phe-Leu-Gln- Pro-Glu or Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu, in the Y-shaped maze test, the amnesia-preventing effect of the composition of the present invention was confirmed by using the rate of change of spontaneous alternation behavior into different arms and the total number of entries into the maze as indices.

In these tests, as a negative control, for example, an animal to which only water is administered can be used. Confirming X-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu-Y (wherein X is absent or represents either Ile or Asn-Ile, wherein Y is absent or represents Val-Met) or X-Val-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu-Y (wherein X is absent or represents either Thr-Gln-Thr-Pro, Pro-Leu-Thr-Gln-Thr-Pro, Leu-Thr-Gln-Thr-Pro or Pro, wherein Y is absent or represents Val-Met), In particular Asn-Ile-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu, or Asn-Ile-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu-Val-Met, or Ile-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu, or Pro-Leu-Thr-Pro-Val-Pro-Phe-Leu-Gln-Val, or Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Pro-Val -Pro-Glu, or Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu, or Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu, or Leu-Thr-Gln-Pro-Val-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu, or Pro-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu, or Val-Val-Pro-Phe-Leu-Gln-Pro-Glu, animals administered with only an agent causing brain dysfunction and inducing amnesia, such as scopolamine, may also be used as controls.

The composition of the present invention or the peptide X-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu-Y (wherein X is absent or represents either Ile or Asn-Ile, wherein Y is absent or represents Val-Met) or the peptide X-Val-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu-Y (wherein X is absent or represents either Thr-Gln-Thr-Pro, Pro-Leu-Thr-Gln-Thr-Pro, or Pro, wherein Y is absent or represents V al-Met), In particular the peptide Asn-Ile-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu, or the peptide Asn-Ile-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu-Val-Met, or the peptide Ile-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu, or the peptide Pro-Pro-Leu-Thr-Pro-Val-Val-Pro-Phe-Leu-Pro-Val-Val-Pro A brain function improving effect of-Gln-Pro-Glu, or a peptide Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu, or a peptide Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu, or a peptide Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu, or a peptide Val-Val-Pro-Phe-Leu-Gln-Pro-Glu, for example, it can be confirmed by performing a novel object recognition test using a rat or a mouse. Specifically, the composition of the present invention or the peptide X-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu-Y (wherein X does not exist or represents either Ile or Asn-Ile, and Y does not exist or represents Val-Met) or the peptide X-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu-Y (wherein X does not exist or represents either Thr-Gln-Thr-Pro, Pro-Leu-Thr-Pro, Leu-Thr-Gln-Thr-Pro, or Leu-Thr-Gln-Thr-Pro, and Y does not exist or represents Val-Met), In particular the peptide Asn-Ile-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu, or the peptide Asn-Ile-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu-Val-Met, or the peptide Ile-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu, or the peptide Pro-Pro-Leu-Thr-Pro-Val-Val-Pro-Phe-Leu-Pro-Val-Val-Pro -Gln-Pro-Glu, or peptide Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu, or peptide Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu, or peptide Leu-Thr-Gln-Thr-Pro-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu, or peptide Pro-Val-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu, or peptide Val-Val-Pro-Phe-Leu-Gln-Pro-Glu, in the test using the experimental box, after a training test for memorizing 2 objects was performed, the memory was removed by the lapse of time, and 1 object of the 2 objects was replaced with a new one, and at this time, if the replaced object was remembered, the memory enhancing effect of the composition of the present invention was confirmed by using the increase of the search time for the new object as an index. In these tests, as a negative control, for example, an animal to which only water is administered can be used.

The active ingredient of the composition of the present invention is a peptide X-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu-Y (wherein X does not exist or represents either Ile or Asn-Ile, and Y does not exist or represents Val-Met), or a peptide X-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu-Y (wherein X does not exist or represents either Thr-Gln-Thr-Pro, Pro-Leu-Thr-Pro, Leu-Thr-Gln-Thr-Pro, or Pro, and wherein Y does not exist or represents Val-Met), In particular the peptide Asn-Ile-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu, or the peptide Asn-Ile-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu-Val-Met, or the peptide Ile-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu, or the peptide Pro-Pro-Leu-Thr-Pro-Val-Val-Pro-Phe-Leu-Pro-Val-Val-Pro -Gln-Pro-Glu, or peptide Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu, or peptide Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu, or peptide Leu-Thr-Gln-Thr-Pro-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu, or peptide Pro-Val-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu, or peptide Val-Val-Pro-Pro-Phe-Leu, the desired effect can be achieved by oral administration or oral ingestion. The administration or intake period of the composition of the present invention may be variously adjusted in consideration of the age of a subject to be administered or taken, for example, a human or non-human animal, the health state of the subject, and the like. The non-human animal includes non-human higher vertebrates, particularly non-human mammals, including pet animals such as dogs and cats, and domestic animals such as cows, horses, pigs, and sheep, but is not limited thereto. The composition of the present invention can be observed as an effect by 1 administration, and a sustained effect can be expected by 1 or more sustained intakes over 1 day. The form of the composition of the present invention when used as a pharmaceutical product may be a form of a preparation for oral administration. Examples thereof include tablets, pills, hard capsules, soft capsules, microcapsules, powders, granules, and liquids. In the case of producing a pharmaceutical product, for example, a pharmaceutically acceptable carrier, excipient, preservative, stabilizer, binder, pH adjuster, buffer, thickener, gelling agent, preservative, antioxidant, etc. may be appropriately used as needed, and the pharmaceutical product may be produced in a unit dose form required for administration of a generally accepted preparation.

The composition of the present invention can also be used as a food or beverage material or an animal feed material, and for example, the composition of the present invention or a peptide X-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu-Y (wherein X does not exist or represents any of Ile or Asn-Ile, and Y does not exist or represents Val-Met) or the peptide X-Val-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu-Y (wherein X does not exist or represents Thr-Gln-Thr-Pro, Pro-Leu-Thr-Gln-Thr-Pro, Thr, or Thr-Gln-Thr-Pro, Leu-Thr-Gln-Thr-Pro or Pro, wherein Y is absent or represents Val-Met), in particular the peptide Asn-Ile-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu, or the peptide Asn-Ile-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu-Val-Met, or the peptide Ile-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu, or, Or the peptide Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu, or the peptide Thr-Gln-Thr-Pro-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu, or the peptide Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu, or the peptide Leu-Th r-Gln-Th r-Pro-Val-Val-Pro-Ph-Leu-Gln-Pro-Glu, or the peptide Pro-Val-Val-Pro-Phe-Leu- Gln-Pro-Glu or peptide Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu is used to prepare functional food such as specific health food with brain function improving effect.

In order to obtain a desired effect, the present composition or the peptide X-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu-Y (wherein X does not exist or represents either Ile or Asn-Ile, and wherein Y does not exist or represents Val-Met) or the peptide X-Val-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu-Y (wherein X does not exist or represents either Thr-Gln-Thr-Pro, Pro-Leu-Thr-Pro, Leu-Thr-Gln-Thr-Pro, or Pro, and wherein Y does not exist or represents Val-Met), In particular the peptide Asn-Ile-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu, or the peptide Asn-Ile-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu-Val-Met, or the peptide Ile-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu, or the peptide Pro-Pro-Leu-Thr-Pro-Val-Val-Pro-Phe-Leu-Pro-Val-Val-Pro An administration or intake dose of-Gln-Pro-Glu, or peptide Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu, or peptide Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu, or peptide Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu, or peptide Val-Val-Pro-Pro-Phe, each of the peptides X-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu-Y (wherein X is absent or represents either Ile or Asn-Ile, and Y is absent or represents Val-Met) or the peptides X-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu-Y (wherein X is absent or represents either Thr-Gln-Thr-Pro, Pro-Leu-Thr-Gln-Thr-Pro, or Pro, and Y is absent or represents either Met-Val), In particular the peptide Asn-Ile-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu, or the peptide Asn-Ile-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu-Val-Met, or the peptide Ile-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu, or the peptide Pro-Pro-Leu-Thr-Pro-Val-Val-Pro-Phe-Leu-Pro-Val-Val-Pro The amount of-Gln-Pro-Glu, or peptide Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu, or peptide Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu, or peptide Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu, or peptide Val-Val-Pro-Phe-Leu-Gln-Pro-Glu is usually preferably 0.1. mu.g- kg body weight to 1mg/kg body weight. The amount of intake per 1 time in a food, for example, a functional food, may be set to an amount lower than the aforementioned amount according to the number of times of intake per 1 day. The appropriate intake amount can be further adjusted in consideration of the above-mentioned various factors.

The composition of the present invention or an active ingredient thereof, i.e., a peptide X-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu-Y (wherein X is absent or represents either Ile or Asn-Ile, and Y is absent or represents Val-Met) or a peptide X-Val-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu-Y (wherein X is absent or represents either Thr-Gln-Thr-Pro, Pro-Leu-Thr-Gln-Thr-Pro, or Pro, y is absent or represents Val-Met), in particular the peptide Asn-Ile-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu, or the peptide Asn-Ile-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu-Val-Met, or the peptide Ile-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu, or the peptide Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val -Pro-Pro-Phe-Leu-Gln-Pro-Glu, or peptide Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu, or peptide Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu, or peptide Leu-Thr-Gln-Thr-Pro-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu, or peptide Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu, or peptide Val-Val-Pro-Pro-Phe-Leu The food such as functional food containing Glu may be supplemented with additives such as saccharides, proteins, lipids, vitamins, minerals, seasonings such as various carbohydrates, lipids, vitamins, minerals, sweeteners, flavors, colors, taste improvers, and mixtures thereof, as necessary, to improve the balance of nutrients and flavor. The composition of the present invention or the peptide X-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu-Y as an active ingredient thereof (wherein X is absent or represents either Ile or Asn-Ile, and Y is absent or represents Val-Met) or the peptide X-Val-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu-Y (wherein X is absent or represents either Thr-Gln-Thr-Pro, Pro-Leu-Thr-Gln-Thr-Pro, or Pro, y is absent or represents Val-Met), in particular the peptide Asn-Ile-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu, or the peptide Asn-Ile-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu-Val-Met, or the peptide Ile-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu, or the peptide Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val -Pro-Pro-Phe-Leu-Gln-Pro-Glu, or peptide Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu, or peptide Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu, or peptide Leu-Thr-Gln-Thr-Pro-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu, or peptide Val-Val-Pro-Pro-Phe-Leu-Gln-Pro- Glu feed for animals can be prepared in the same manner as food for human use.

For example, the functional food may be in the form of a solid, a gel, or a liquid, and examples thereof include various processed foods and drinks, dried powders, tablets, capsules, granules, and the like, and further, various beverages, yogurt, liquid foods, jellies, candies, retort pouch foods (ready food), refreshing fruit pieces, cookies, cakes, breads, biscuits, chocolates, and the like.

In the production of a functional food such as a specific health food containing the composition of the present invention, depending on the form of addition and the form of the product, the active ingredient contained in the final product is the peptide X-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu-Y (wherein X does not exist or represents Val-Met) or the peptide X-Val-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu-Y (wherein X does not exist or represents Thr-Gln-Thr-Pro, Pro-Leu-Thr-Gln-Thr-Pro, or Thr-Gln-Thr-Pro, Leu-Thr-Gln-Thr-Pro or Pro, wherein Y is absent or represents Val-Met), in particular the peptide Asn-Ile-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu, or the peptide Asn-Ile-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu-Val-Met, or the peptide Ile-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu, or, Or the peptide Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu, or the peptide Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu, or the peptide Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu, or the peptide Leu-Thr-Gln-Thr-Pro-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu, or the peptide Pro-Val-Val-Pro-Pro- The content of Glu or peptide Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu is adjusted so that the amount of Glu or peptide Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu per 100g is 1. mu.g to 10g, preferably 10. mu.g to 1g, and more preferably 100. mu.g to 100 mg.

The composition of the present invention or the peptide X-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu-Y as an active ingredient thereof (wherein X does not exist or represents either Ile or Asn-Ile, and Y does not exist or represents Val-Met) or the peptide X-Val-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu-Y (wherein X does not exist or represents either Thr-Gln-Thr-Pro, Pro-Leu-Thr-Gln-Thr-Pro, Leu-Thr-Gln-Thr-Pro or Pro, y is absent or represents Val-Met), in particular the peptide Asn-Ile-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu, or the peptide Asn-Ile-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu-Val-Met, or the peptide Ile-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu, or the peptide Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val -Pro-Pro-Phe-Leu-Gln-Pro-Glu, or peptide Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu, or peptide Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu, or peptide Leu-Thr-Gln-Thr-Pro-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu, or peptide Val-Val-Pro-Pro-Phe-Leu-Gln-Pro- Glu can improve brain function, thereby preventing amnesia and improving memory. In addition, the composition of the present invention or the aforementioned peptide as an active ingredient thereof can be used for the treatment or prevention of symptoms and diseases due to cerebral hypofunction, such as depression, integration disorder, delirium, senile dementia (cerebrovascular senile dementia, alzheimer's disease, etc.), and the like.

The present invention will be described more specifically with reference to the following examples, but the scope of the present invention is not limited to the examples.

[ example 1 ]

Amnesia preventing effect of Asn-Ile-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu (NIPPLTQTPVVPPFLQPE)

Male mice of ddY line (about 7 weeks old) (n = 15-75) were used, and were allowed to freely take feed and water. As the test substances, Asn-Ile-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu was used at 0.05nmol/kg body weight (0.1. mu.g/kg body weight), 0.5nmol/kg body weight (1. mu.g/kg body weight), 1.5nmol/kg body weight (3. mu.g/kg body weight), 5nmol/kg body weight (10. mu.g/kg body weight), 50nmol/kg body weight (100. mu.g/kg body weight), and 500nmol/kg body weight (1000. mu.g/kg body weight). The test substance was orally administered to the mice in a single dose 60 minutes before the Y-maze test for evaluation of spontaneous alternation behavior was performed. Furthermore, scopolamine was subcutaneously administered to the back at 1mg/kg body weight in order to induce brain dysfunction (dysmnesia and/or cognitive dysfunction) in mice 30 minutes before the Y-maze test was performed. In the Y-maze test, a Y-maze in which 3 arms each having an arm length of 40cm, a wall height of 12cm, a bottom width of 3cm and an upper width of 10cm are connected at an angle of 120 degrees was used as an experimental apparatus. The mouse was placed at the tip of any arm of the Y-maze, allowed to freely explore within the maze for 8 minutes, and the arms passed by the mouse were sequentially recorded. The number of times the mouse walked into each arm in the measurement time was counted as a total number of entries, and combinations in which three different arms were successively selected (for example, when 3 arms were A, B, C, the number of entries was 4 including the number of repetitions in the case where the order of the arms was abcbcaca) were investigated as a number of spontaneous alternation behaviors. The spontaneous alternation behavior number is divided by a number obtained by subtracting 2 from the total entry number, and then multiplied by 100, and the obtained value is used as the spontaneous alternation behavior change rate, which is used as the indicator of the spontaneous alternation behavior. Higher index values indicate more retention of short-term memory. The measured values are expressed as mean. + -. standard error per group. The significance test of the differences between the control group and the scopolamine control group was performed by Student (Student) t test. In addition, the differential significance test of the scopolamine control group and the NIPPLTQTPVVVPPFLQPE-administered group was performed using a Dunnett (Dunnett) type multiple comparison test after one-way anova. The results are shown in FIG. 1. NIPPLTQTPVVVPPFLQPE shows that it has amnesia preventing effect in the range of 0.05nmol/kg body weight to 500nmol/kg body weight (0.1. mu.g/kg body weight to 1000. mu.g/kg body weight).

[ example 2 ]

Amnesia preventing effect of Asn-Ile-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu (NIPPLTQTPVVPPFLQPE) related peptide

Male mice of ddY line (about 7 weeks old) (n = 15-45) were used, and were allowed to freely take in feed and water. As the test substance, Asn-Ile-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu 50nmol/kg body weight (100. mu.g/kg body weight), or Asn-Ile-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu-Val-Met (NIPPLTPVVVPFLQPEVM) 50nmol/kg body weight (120. mu.g/kg body weight), or Ile-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu (IPPLTQVPVPPFL QPE) 50nmol/kg body weight (100. mu.g/kg body weight), or Ile-Pro-Pro-Leu-Thr (100. mu.g/kg body weight), or Asn-Ile-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro (NIPPLTQTPVVVPFLQP) (SEQ ID NO: 18) 50nmol/kg body weight (100. mu.g/kg body weight), or Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Phe (TQTPVVPPF) (SEQ ID NO: 19) 50nmol/kg body weight (50. mu.g/kg body weight). The test substance was orally administered to the mice in a single dose 60 minutes before the Y-maze test for evaluation of spontaneous alternation behavior was performed. Furthermore, scopolamine was subcutaneously administered to the back at 1mg/kg body weight in order to induce brain dysfunction (dysmnesia and/or cognitive dysfunction) in mice 30 minutes before the Y-maze test was performed. In the Y-maze test, a Y-maze in which 3 arms each having an arm length of 40cm, a wall height of 12cm, a bottom width of 3cm and an upper width of 10cm are connected at an angle of 120 degrees was used as an experimental apparatus. The mouse was placed at the tip of any arm of the Y-maze, allowed to freely explore within the maze for 8 minutes, and the arms passed by the mouse were sequentially recorded. The number of times the mouse walked into each arm in the measurement time was counted as a total number of entries, and combinations in which three different arms were successively selected (for example, when 3 arms were A, B, C, the number of entries was 4 including the number of repetitions in the case where the order of the arms was abcbcaca) were investigated as a number of spontaneous alternation behaviors. The spontaneous alternation behavior number is divided by a number obtained by subtracting 2 from the total entry number, and then multiplied by 100, and the obtained value is used as the spontaneous alternation behavior change rate, which is used as the indicator of the spontaneous alternation behavior. Higher index values indicate more retention of short-term memory. The measured values are expressed as mean. + -. standard error per group. The significance test of the differences between the control group and the scopolamine control group was performed by Student (Student) t test. In addition, the differential significance test for the scopolamine control group and each peptide-administered group was performed using a Dunnett (Dunnett) type multiple comparison test after one-way anova. The results are shown in FIG. 2. NIPPLTQTPVVVPPFLQPE was shown to have amnesic effects at 50nmol/kg body weight (100. mu.g/kg body weight), NIPPLTQTPVVVPPFLQPEVM at 50nmol/kg body weight (120. mu.g/kg body weight), IPPLTQTPVVVPPFLQPE at 50nmol/kg body weight (100. mu.g/kg body weight). NIPPLTQTPVVVPPFLQP at 50nmol/kg body weight (100. mu.g/kg body weight) and TQTPVVVPPF at 50nmol/kg body weight (50. mu.g/kg body weight) did not see significant differences compared to the scopolamine control group, indicating no amnesic effect.

[ example 3 ]

Asn-Ile-Pro-Pro-Leu-Thr-Gln-Thr-PAmnesia prevention effect of ro-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu (NIPPLTQTPVVVPFLQPE) related peptide

Male mice of ddY line (about 7 weeks old) (n = 14-15) were used, and were allowed to freely take in feed and water. As the test substance, Asn-Ile-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu 500nmol/kg body weight (1000. mu.g/kg body weight) or Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu (PPLTQTPVVVVPQPFLE) 500nmol/kg body weight (1000. mu.g/kg body weight) was used. The test substance was orally administered to the mice in a single dose 60 minutes before the Y-maze test for evaluation of spontaneous alternation behavior was performed. Furthermore, scopolamine was subcutaneously administered to the back at 1mg/kg body weight in order to induce brain dysfunction (dysmnesia and/or cognitive dysfunction) in mice 30 minutes before the Y-maze test was performed. In the Y-maze test, a Y-maze in which 3 arms each having an arm length of 40cm, a wall height of 12cm, a bottom width of 3cm and an upper width of 10cm are connected at an angle of 120 degrees was used as an experimental apparatus. The mouse was placed at the tip of any arm of the Y-maze, allowed to freely explore within the maze for 8 minutes, and the arms passed by the mouse were sequentially recorded. The number of times the mouse walked into each arm in the measurement time was counted as a total number of entries, and combinations in which three different arms were successively selected (for example, when 3 arms were A, B, C, the number of entries was 4 including the number of repetitions in the case where the order of the arms was abcbcaca) were investigated as a number of spontaneous alternation behaviors. The spontaneous alternation behavior number is divided by a number obtained by subtracting 2 from the total entry number, and then multiplied by 100, and the obtained value is used as the spontaneous alternation behavior change rate, which is used as the indicator of the spontaneous alternation behavior. Higher index values indicate more retention of short-term memory. The measured values are expressed as mean. + -. standard error per group. The significance test of the differences between the control group and the scopolamine control group was performed by Student (Student) t test. In addition, the differential significance test for the scopolamine control group and each peptide-administered group was performed using a Dunnett (Dunnett) type multiple comparison test after one-way anova. The results are shown in FIG. 3. NIPPLTQTPVVVPPFLQPE shows that NIPPLTQTPVVVPPFLQPE has the function of preventing amnesia under the conditions of 500nmol/kg body weight (1000 mug/kg body weight) and PPLTQTPVVVPPFLQPE under the conditions of 500nmol/kg body weight (1000 mug/kg body weight).

[ example 4 ]

Memory enhancing effect of Asn-Ile-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu (NIPPLTQTPVVPPFLQPE)

Male mice of ddY line (about 7 weeks old) (n = 14-15) were used, and were allowed to freely take in feed and water. As the test substance, Asn-Ile-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu was used at 500nmol/kg body weight (1000. mu.g/kg body weight). The test substance was administered orally to mice in a single dose 60 minutes before conducting a new object recognition test for evaluating memory retention. In the new object recognition test, a 30X 30cm box was used as an experimental apparatus. As the acclimatization operation, the mice were placed in an experimental apparatus on which a mat was laid for 5 minutes, and the apparatus was freely searched. The next day of acclimatization operation training trials were performed. In the training test, 2 objects selected from 3 kinds of objects were set in the experimental apparatus (the objects were placed at positions 8cm from both side walls along the center line of the bottom of the tank, and the positions were set to X1 and X2), and the selection of the set objects was randomly selected in advance so as not to deviate between animals and groups. After 60 minutes of oral administration of the test substance or water, the mice were placed in the experimental apparatus for 5 minutes, and the time (seconds) for the mice to approach the objects within 1cm and search for the objects was measured. The holding test was performed after 48 hours of the training test. In the holding test, 2 objects were set in the experimental apparatus in the same manner as in the training test, and 1 of the 2 objects was replaced with an object (new object) different from the object used in the training test, and the position thereof was set to Y. (for example, in the training test, when the object a was set at X1 and the object B was set at X2, and in the holding test, a new object C was set in place of the object a, and the position thereof was set at Y.) the time (seconds) for which the mouse was searched for within 1cm of the proximity of each object was measured for the training test and the holding test. (the state on the object was not included) for the training test and the holding test, the ratio of the time during which 2 objects were searched for each was obtained. The ratio (%) of the search time for each object is expressed as the mean ± standard error per group. In the significance test of the difference, Student (Student) t-test was performed between the control group and the peptide group on the ratio of the search time for the novelty object (object set at Y) in the retention test and the ratio of the search time for the object set at the position of the novelty object (object set at X1 or X2) in the training test. The results are shown in FIG. 4. NIPPLTQTPVVVPPFLQPE was shown to have memory enhancing effect at 500nmol/kg body weight (1000. mu.g/kg body weight).

[ example 5 ]

Amnesia preventing effect of Asn-Ile-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu (NIPPLTQTPVVPPFLQPE) related peptide

Male mice of ddY line (about 7 weeks old) (n = 27-40) were used, and were allowed to freely take in feed and water. As the test substance, Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu (TQTPVVPPFLQPE) 50nmol/kg body weight (80. mu.g/kg body weight) was used. The test substance was orally administered to the mice in a single dose 60 minutes before the Y-maze test for evaluation of spontaneous alternation behavior was performed. Furthermore, scopolamine was subcutaneously administered to the back at 1mg/kg body weight in order to induce brain dysfunction (dysmnesia and/or cognitive dysfunction) in mice 30 minutes before the Y-maze test was performed. In the Y-maze test, a Y-maze in which 3 arms each having an arm length of 40cm, a wall height of 12cm, a bottom width of 3cm and an upper width of 10cm are connected at an angle of 120 degrees was used as an experimental apparatus. The mouse was placed at the tip of any arm of the Y-maze, allowed to freely explore within the maze for 8 minutes, and the arms passed by the mouse were sequentially recorded. The number of times the mouse walked into each arm in the measurement time was counted as a total number of entries, and combinations in which three different arms were successively selected (for example, when 3 arms were A, B, C, the number of entries was 4 including the number of repetitions in the case where the order of the arms was abcbcaca) were investigated as a number of spontaneous alternation behaviors. The spontaneous alternation behavior number is divided by a number obtained by subtracting 2 from the total entry number, and then multiplied by 100, and the obtained value is used as the spontaneous alternation behavior change rate, which is used as the indicator of the spontaneous alternation behavior. Higher index values indicate more retention of short-term memory. The measured values are expressed as mean. + -. standard error per group. The significance test of the differences between the control group and the scopolamine control group was performed by Student (Student) t test. In addition, the differential significance test of the scopolamine control group and the TQTPVVVPPFLQPE administration group was performed by Student (Student) t test. The results are shown in FIG. 5. TQTPVVVPPFLQPE was shown to have amnesia preventing effect at 50nmol/kg body weight (80. mu.g/kg body weight).

[ example 6 ]

Amnesia preventing effect of Asn-Ile-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu (NIPPLTQTPVVPPFLQPE) related peptide

Male mice of ddY line (about 7 weeks old) (n = 11-40) were used, and were allowed to freely take in feed and water. Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu (PLTQTPVVVPPFLQPE) 500nmol/kg body weight (900. mu.g/kg body weight), or Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu (LTQTPVVVVPPPFLQPE) 500nmol/kg body weight (850. mu.g/kg body weight), or Pro-Val-Val-Val-Pro-Phe-Leu-Gln-Pro-Glu (PVVVPFLQPE) 500nmol/kg body weight (630. mu.g/kg body weight), or Pro-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-VVVGlu (PFQPE) 500nmol/kg body weight (PFLQPE) 580. mu.g/kg body weight). The test substance was orally administered to the mice in a single dose 60 minutes before the Y-maze test for evaluation of spontaneous alternation behavior was performed. Furthermore, scopolamine was subcutaneously administered to the back at 1mg/kg body weight in order to induce brain dysfunction (dysmnesia and/or cognitive dysfunction) in mice 30 minutes before the Y-maze test was performed. In the Y-maze test, a Y-maze in which 3 arms each having an arm length of 40cm, a wall height of 12cm, a bottom width of 3cm and an upper width of 10cm are connected at an angle of 120 degrees was used as an experimental apparatus. The mouse was placed at the tip of any arm of the Y-maze, allowed to freely explore within the maze for 8 minutes, and the arms passed by the mouse were sequentially recorded. The number of times the mouse walked into each arm in the measurement time was counted as a total number of entries, and combinations in which three different arms were successively selected (for example, when 3 arms were A, B, C, the number of entries was 4 including the number of repetitions in the case where the order of the arms was abcbcaca) were investigated as a number of spontaneous alternation behaviors. The spontaneous alternation behavior number is divided by a number obtained by subtracting 2 from the total entry number, and then multiplied by 100, and the obtained value is used as the spontaneous alternation behavior change rate, which is used as the indicator of the spontaneous alternation behavior. Higher index values indicate more retention of short-term memory. The measured values are expressed as mean. + -. standard error per group. The significance test of the differences between the control group and the scopolamine control group was performed by Student (Student) t test. In addition, the differential significance test of the scopolamine control group and each peptide administration group was performed by Student (Student) t test. The results are shown in FIG. 6. PLTQTPVVVPPFLQPE was shown to have amnesic effects at 500nmol/kg body weight (900. mu.g/kg body weight), LTQTPVVVPPFLQPE at 500nmol/kg body weight (850. mu.g/kg), PVVVPPFLQPE at 500nmol/kg body weight (630. mu.g/kg), VVVPPFLQPE at 500nmol/kg body weight (580. mu.g/kg).

Reference to the literature

1. Japanese patent No. 3898389

2．Science,217,408-414(1982)

Claims (21)

1. A composition for preventing amnesia or enhancing memory comprises peptide or its salt having amino acid sequence X-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu-Y as effective component,

1) x represents Asn-Ile-Pro-Pro-Leu-Thr-Gln-Thr-Pro, or Leu-Thr-Gln-Thr-Pro,

the presence of Y is not present and,

or the like, or, alternatively,

2) x represents Asn-Ile-Pro-Pro-Leu-Thr-Gln-Thr-Pro, or Leu-Thr-Gln-Thr-Pro,

y represents Val-Met.

2. A composition for preventing amnesia or improving memory contains Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu or its salt as effective component.

3. A composition for preventing amnesia or enhancing memory comprises Ile-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu or its salt as effective component.

4. A composition for preventing amnesia or improving memory contains Asn-Ile-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu or its salt as effective component.

5. A composition for preventing amnesia or enhancing memory comprises Asn-Ile-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu-Val-Met or its salt as effective component.

6. A composition for preventing amnesia or improving memory contains Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu or its salt as effective component.

7. The composition according to any one of claims 1 to 6, which is for oral ingestion.

8. Use of a peptide consisting of the amino acid sequence X-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu-Y or a salt thereof as an active ingredient in the preparation of a medicament for the prevention of amnesia or for the enhancement of memory, wherein,

1) x represents Asn-Ile-Pro-Pro-Leu-Thr-Gln-Thr-Pro, or Leu-Thr-Gln-Thr-Pro,

the presence of Y is not present and,

or the like, or, alternatively,

2) x represents Asn-Ile-Pro-Pro-Leu-Thr-Gln-Thr-Pro, or Leu-Thr-Gln-Thr-Pro,

y represents Val-Met.

9. The application of the peptide consisting of amino acid sequence Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu or the salt thereof in preparing the drugs for preventing amnesia or enhancing memory.

10. Use of a peptide consisting of the amino acid sequence Ile-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu or a salt thereof in the preparation of a medicament for preventing amnesia or enhancing memory.

11. Use of a peptide consisting of an amino acid sequence Asn-Ile-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu or a salt thereof in the preparation of a medicament for preventing amnesia or enhancing memory.

12. The application of the peptide or the salt thereof consisting of the amino acid sequence Asn-Ile-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu-Val-Met in the preparation of the drugs for preventing amnesia or enhancing memory.

13. The use of a peptide consisting of the amino acid sequence Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu or a salt thereof in the preparation of a medicament for preventing amnesia or enhancing memory.

14. The application of the peptide consisting of the amino acid sequence Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu or the salt thereof in preparing the drugs for preventing amnesia or enhancing memory.

15. The use according to any one of claims 8 to 14, wherein the medicament is for oral administration.

16. A peptide consisting of the amino acid sequence X-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu-Y, wherein,

1) x represents Asn-Ile-Pro-Pro-Leu-Thr-Gln-Thr-Pro, or Leu-Thr-Gln-Thr-Pro,

the presence of Y is not present and,

or the like, or, alternatively,

2) x represents Asn-Ile-Pro-Pro-Leu-Thr-Gln-Thr-Pro, or Leu-Thr-Gln-Thr-Pro,

y represents Val-Met.

17. A peptide consisting of an amino acid sequence Asn-Ile-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu (SEQ ID NO:3) or a salt thereof.

18. A peptide consisting of an amino acid sequence Asn-Ile-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu-Val-Met (SEQ ID NO:6) or a salt thereof.

19. A peptide consisting of an amino acid sequence Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu (SEQ ID NO:1) or a salt thereof.

20. A peptide consisting of the amino acid sequence Ile-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu (SEQ ID NO:2) or a salt thereof.

21. A peptide consisting of the amino acid sequence Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu (SEQ ID NO:9) or a salt thereof.