WO2003066672A1

WO2003066672A1 - Peptides

Info

Publication number: WO2003066672A1
Application number: PCT/JP2003/001333
Authority: WO
Inventors: Kenji Sakamoto
Original assignee: Nakoshi, Hideo
Priority date: 2002-02-08
Filing date: 2003-02-07
Publication date: 2003-08-14
Also published as: AU2003211501A1; JPWO2003066672A1

Abstract

It is intended to provide peptides which are particularly useful as drugs and foods. This object can be achieved by providing peptides having specific amino acid sequences which exert effects of promoting the production of insulin, controlling the secretion of gastric juice, promoting the production of growth hormone, lowering blood pressure, inhibiting fat accumulation, controlling allergy, relieving pain and promoting the central nerve system functions. Using these peptides, novel drugs, foods, etc. having the above functions can be obtained.

Description

Description Peptide Technical Field

The present invention relates to peptides. More specifically, the present invention relates to a peptide having an insulin production promoting effect, a gastric acid secretion suppressing effect, a growth hormone production promoting effect, a blood pressure lowering effect, a fat accumulation suppressing effect, an allergy suppressing effect, an analgesic effect, and a central nervous system function promoting effect. Background art

There has been a demand for the development of pharmaceuticals that have excellent efficacy and no disadvantages such as side effects. On the other hand, it is a well-known fact that many biologically active substances exist in living organisms and are closely involved in maintaining normal living activities of living organisms. These in vivo physiologically active substances and synthetic physiologically active substances themselves have potential as new medicines, foods, etc., and also provide knowledge for developing new medicines, foods, etc.

An object of the present invention is to provide a peptide which is particularly useful as a medicine or food. Disclosure of the invention

The inventors of the present invention have conducted intensive studies to solve the above problems, and as a result, have found that a peptide having a specific amino acid sequence has excellent physiological activity and is particularly useful as a medicine or a food. Was completed.

That is, the present invention relates to a peptide having the amino acid sequence represented by SEQ ID NO: 1 in the sequence listing, or substitution or deletion of one or more amino acids in the amino acid sequence, or substitution of one or more amino acids in the amino acid sequence. Has an amino acid sequence in which multiple amino acids have been inserted or added. Such as a peptide having an insulin production promoting effect, a peptide comprising the peptide as an active ingredient, an insulin production enhancer comprising these peptides, and an insulin production enhancer comprising the peptide as an active ingredient. Medicine or food.

Further, the present invention relates to a peptide having an amino acid sequence represented by SEQ ID NO: 2 in the sequence listing, or one or more amino acids in the amino acid sequence are substituted or deleted, or one or more amino acids are substituted in the amino acid sequence. A peptide having an amino acid sequence in which a plurality of amino acids are inserted or added, the peptide having a gastric acid secretion inhibitory effect, a peptide containing the peptide as an active ingredient, a gastric acid secretion inhibitor comprising these peptides, and It is a medicine or food such as a gastric acid secretion inhibitor containing the above-mentioned peptide as an active ingredient.

Further, the present invention relates to a peptide having an amino acid sequence represented by SEQ ID NO: 3 in the sequence listing, or one or more amino acids in the amino acid sequence are substituted or deleted, or one or more amino acids are substituted in the amino acid sequence. A peptide having an amino acid sequence in which a plurality of amino acids are inserted or added, the peptide having a growth hormone production promoting effect, a peptide containing the peptide as an active ingredient, and a growth hormone production comprising these peptides And a medicament or a food such as a growth hormone production promoter containing the above-mentioned peptide as an active ingredient.

Furthermore, the present invention relates to a peptide having the amino acid sequence represented by SEQ ID NO: 4, 5, 6, 7, 8, 9, 10, 11, or 12 in the sequence listing, or 1 Or a peptide having an amino acid sequence in which a plurality of amino acids are substituted or deleted, or in which one or more amino acids are inserted or added to the amino acid sequence, and which has a blood pressure lowering effect. Pharmaceuticals or foods such as a peptide containing the peptide as an active ingredient, a blood pressure lowering agent comprising these peptides, and a blood pressure lowering agent containing the peptide as an active ingredient.

Further, the present invention relates to a peptide having the amino acid sequence represented by SEQ ID NO: 13, 14, 15, 15, 16, 17 or 18 in the sequence listing, A peptide having an amino acid sequence in which one or more amino acids in the amino acid sequence have been substituted or deleted, or an amino acid sequence in which one or more amino acids have been inserted or added to the amino acid sequence, and Pharmaceuticals or foods such as peptides having an antibacterial effect, peptides containing the peptides as active ingredients, fat accumulation inhibitors composed of these peptides, and fat accumulation inhibitors containing the peptides as active ingredients. ₍ Also, the present invention provides a peptide having an amino acid sequence represented by SEQ ID NO: 19 in the sequence listing, or a substitution or deletion of one or more amino acids in the amino acid sequence, or A peptide having an amino acid sequence in which one or more amino acids are inserted or added, wherein the peptide has an allergy-suppressing effect; Peptide to the peptide as an active ingredient, a pharmaceutical or a food such as those § les-saving one inhibitor consisting of peptides, and allele formic one inhibitor comprising the base peptide as an active ingredient.

Further, the present invention relates to a peptide having an amino acid sequence represented by SEQ ID NO: 20, 21, or 22, or one or more amino acids in the amino acid sequence are substituted or deleted, or the amino acid A peptide having an amino acid sequence in which one or more amino acids are inserted or added to the sequence, the peptide having a blood pressure lowering effect, a peptide containing the peptide as an active ingredient, a blood pressure lowering agent comprising these peptides And a medicine or food, such as a hypotensive agent, containing the above-mentioned peptide as an active ingredient.

Further, the present invention provides a peptide having the amino acid sequence represented by SEQ ID NO: 23 or 24, or substitution or deletion of one or more amino acids in the amino acid sequence, or Or a peptide having an amino acid sequence in which a plurality of amino acids are inserted or added, the peptide having an analgesic effect, a peptide containing the peptide as an active ingredient, an analgesic comprising the peptide, and the aforementioned It is a drug or food such as an analgesic containing a peptide as an active ingredient. Further, the present invention relates to a peptide having the amino acid sequence represented by SEQ ID NO: 25, 26, 27, 28, 29, 30, 31 or 32, or 1 Or a peptide having an amino acid sequence in which a plurality of amino acids are substituted or deleted, or in which one or more amino acids are inserted or added to the amino acid sequence, and which has a central nervous system function promoting effect. Pharmaceuticals or foods such as a peptide, a peptide containing the peptide as an active ingredient, a central nervous system function promoter comprising the peptide, and a central nervous system function promoter containing the peptide as an active ingredient. BEST MODE FOR CARRYING OUT THE INVENTION

The peptide according to the first invention of the present invention is a peptide having an amino acid sequence represented by SEQ ID NO: 1 in the sequence listing. Since the peptide has a function of promoting insulin production, it is useful as an insulin production promoter and is applied to medicines, foods, and the like. For example, the peptide according to the first invention is blended as an active ingredient, and is applied to medicines, foods, etc., such as insulin production promoters. Among these, the insulin production promoter as a medicament can be used for the treatment and prevention of diabetes, and its application as a therapeutic agent for diabetes is also included in the category of the insulin production promoter of the present invention.

In general, even when a peptide having a physiological activity has a small number of amino acid sequences substituted or deleted in the amino acid sequence, or a small number of amino acid sequences inserted or added to the amino acid sequence. It is well known to those skilled in the art that the physiological activity may be maintained. Therefore, one or more amino acids in the amino acid sequence shown in SEQ ID NO: 1 are substituted or deleted, or a peptide having an amino acid sequence in which one or more amino acids are inserted or added to the amino acid sequence. Further, peptides having an insulin production promoting effect are also included in the scope of the peptides according to the first invention of the present invention. The amino acid sequence of such a peptide is shown in SEQ ID NO: It is preferred that it has 70% or more, more preferably 90% or more homology with the amino acid sequence represented by 1.

It is preferable that the insulin production promoting agent as the medicament according to the first invention is administered orally administered by a parenteral route such as intravenous injection, subcutaneous injection, intramuscular injection, or rectal administration. The dosage is determined appropriately based on the condition of the patient, the molecular weight of the active ingredient, and the like. Usually, for parenteral administration, the body weight is preferably 1 kg and the daily dose is preferably about 0.1 mg to 0.1 mg. In the case of oral administration, the weight is preferably about 1 kg and about 0.1 mg to 1 Omg per day. In addition, the insulin production promoter comprising the peptide according to the first invention can be appropriately formulated by a conventional method. For example, the insulin production promoter is dissolved in physiological saline in a concentration range of 30 mg / l to 300 mg Z1. Can be used. In the case of oral administration, it can be added to beverages to form a so-called drink.

The peptide according to the second invention of the present invention is a peptide having an amino acid sequence represented by SEQ ID NO: 2 in the sequence listing. Since the peptide has a function of suppressing gastric acid secretion, it is useful as a gastric acid secretion inhibitor and is applied to medicines, foods, and the like. For example, the peptide according to the second invention is blended as an active ingredient and applied to medicines, foods and the like such as gastric acid secretion inhibitors. Among these, the gastric acid secretion inhibitor as a medicament can be used for treatment and prevention of gastric ulcer and duodenal ulcer, and the application as a gastrointestinal drug is also included in the scope of the gastric acid secretion inhibitor of the present invention. As in the case of the insulin production promoter, one or more amino acids in the amino acid sequence shown in SEQ ID NO: 2 are substituted or deleted, or one or more amino acids are inserted in the amino acid sequence, or Peptides having an added amino acid sequence and having a gastric acid secretion inhibitory effect are also included in the scope of the peptides according to the second invention of the present invention. It is preferable that the amino acid sequence of such a peptide has 70% or more, more preferably 90% or more homology with the amino acid sequence represented by SEQ ID NO: 2. The gastric acid secretion inhibitor as a medicament according to the second invention is preferably administered by a parenteral route such as intravenous injection, subcutaneous injection, intramuscular injection, or rectal administration, or orally. The dosage is determined appropriately based on the condition of the patient, the molecular weight of the active ingredient, and the like.In general, for parenteral administration, the body weight is preferably 1 kg and the daily dose is preferably about 0.01 mg to 1 mg. However, in the case of oral administration, the body weight is preferably 1 kg, and about 0.1 to 10 mg per day is preferable. Further, the gastric acid secretion inhibitor comprising the peptide according to the second invention can be appropriately formulated by a conventional method, for example, a concentration of 30 mgZl to 300 mg / l in physiological saline. It is possible to use those dissolved within the range. In the case of oral administration, a so-called drink can be added to a beverage.

The peptide according to the third invention of the present invention is a peptide having an amino acid sequence represented by SEQ ID NO: 3 in the sequence listing. Since the peptide has a function of promoting the production of growth hormone, it is useful as a growth hormone production promoter and is applied to medicines, foods, and the like. For example, the above-mentioned peptide according to the third aspect of the present invention is blended as an active ingredient and applied to pharmaceuticals such as growth hormone production promoters, foods and the like. Among them, the growth hormone production promoter as a medicine can be used for treating dwarfism.

As in the case of the insulin production promoter, one or more amino acids in the amino acid sequence shown in SEQ ID NO: 3 are substituted or deleted, or one or more amino acids are inserted into the amino acid sequence or Peptides having an added amino acid sequence and having a growth hormone production promoting effect are also included in the scope of the peptide according to the third invention of the present invention. It is preferable that the amino acid sequence of such a peptide has 70% or more, more preferably 90% or more homology with the amino acid sequence represented by SEQ ID NO: 3.

The growth hormone production promoter as a medicament according to the third invention is preferably administered by a parenteral route such as intravenous injection, subcutaneous injection, intramuscular injection, or rectal administration, or orally. Also, the dose depends on the patient It is appropriately determined based on the condition of the individual, the molecular weight of the active ingredient, etc., but in general, the body weight is preferably 1 kg for parenteral administration and about 0.01 to 1 mg per day, and the weight for oral administration. 1 kg, about 0.1 mg to 10 mg per day is preferable. Further, the growth hormone production promoter comprising the peptide according to the third invention can be appropriately formulated by a conventional method, for example, in a concentration range of 30 mgZl to 300 mgZ1 in physiological saline. A dissolved one can be used. In the case of oral administration, a so-called drink can be added to a beverage.

The peptide according to the fourth invention of the present invention is a peptide having an amino acid sequence represented by SEQ ID NO: 4, 5, 6, 7, 8, 9, 10, 11, or 12 in the sequence listing. Since the peptide has a function of lowering blood pressure, it is useful as a blood pressure lowering agent, and is applied to medicines, foods, and the like. For example, the above-mentioned peptide according to the fourth aspect of the present invention is blended as an active ingredient, and is applied to medicines, foods and the like such as antihypertensive agents. Among them, the antihypertensive agent as a medicament can be used for treatment and prevention of hypertension, and its application as an antihypertensive agent is also included in the category of the antihypertensive agent of the present invention.

As in the case of the insulin production promoter, one or more amino acids in the amino acid sequence shown in SEQ ID NO: 4, 5, 6, 7, 8, 9, 10, 11, or 12 are substituted. A peptide having an amino acid sequence in which the amino acid sequence is deleted or deleted, or one or more amino acids are inserted or added in the amino acid sequence, and which has a blood pressure lowering effect is also a fourth invention of the present invention. Are included in the range of peptides according to The amino acid sequence of such a peptide has at least 70%, more preferably at least 90%, the amino acid sequence represented by SEQ ID NOs: 4, 5, 6, 7, 8, 9, 10, 11, or 12. Preferably, they have homology.

The antihypertensive agent as a medicament according to the fourth aspect of the present invention is preferably administered by a parenteral route such as intravenous injection, subcutaneous injection, intramuscular injection, rectal administration or oral administration. Dosage may vary depending on patient condition and It is determined as appropriate based on the molecular weight of the active ingredient, etc., but in general, parenteral administration is preferably lkg in body weight, and 0.0 lmg per day or more: about Lmg is preferable. About 0.1 to 10 mg per day is preferred. The antihypertensive agent comprising the peptide according to the fourth aspect of the present invention can be appropriately formulated by a conventional method.For example, a solution obtained by dissolving in a physiological saline solution in a concentration range of 30 mg / l to 300 OmgZl is used. Can be used. In the case of oral administration, a so-called drink can be added to a beverage.

The peptide according to the fifth invention of the present invention is a peptide having an amino acid sequence represented by SEQ ID NO: 13, 14, 15, 16, 17 or 18 in the sequence listing. Since the peptide has a function of suppressing fat accumulation (fat accumulation suppressing effect), it is useful as a fat accumulation inhibitor, and is applied to medicines, foods, and the like. For example, the peptide according to the fifth aspect of the present invention is blended as an active ingredient, and is applied to medicines, foods and the like such as fat accumulation inhibitors. Among them, the fat accumulation inhibitor as a medicament can be used for the treatment and prevention of hypolipidemia, and the fat accumulation inhibitor of the present invention can be used as an agent for hyperlipidemia, a therapeutic agent for obesity, and an agent for preventing obesity. It is included in the category of accumulation inhibitors.

In general, even when a peptide having a physiological activity has a small number of amino acid sequences substituted or deleted in the amino acid sequence, or a small number of amino acid sequences inserted or added to the amino acid sequence. It is well known to those skilled in the art that the physiological activity may be maintained. Therefore, one or more amino acids in the amino acid sequence shown in SEQ ID NO: 13, 14, 15, 15, 16, 17 or 18 are substituted or deleted, or one or more amino acids are added to the amino acid sequence. Peptides having an amino acid sequence in which the amino acid is inserted or added and having an effect of suppressing fat accumulation are also included in the scope of the peptide according to the fifth invention of the present invention. The amino acid sequence of such a peptide is at least 70%, more preferably at least 90%, the amino acid sequence represented by SEQ ID NOS: 13, 14, 15, 16, 17 or 18. It is preferable to have the above homology.

The fat accumulation inhibitor as a medicament according to the fifth invention is preferably administered by a parenteral route such as intravenous injection, subcutaneous injection, intramuscular injection, or rectal administration, or orally. The dosage is determined appropriately based on the condition of the patient, the molecular weight of the active ingredient, and the like.In general, for parenteral administration, the body weight is preferably 1 kg and the daily dose is preferably about 0.01 mg to 1 mg. In the case of oral administration, the body weight is preferably 1 kg and about 0.1 to 10 mg per day. In addition, the fat accumulation inhibitor comprising the peptide according to the fifth invention can be appropriately formulated by a conventional method.For example, 30 mg / l to 300 mg / l of physiological saline can be used. Those dissolved in the concentration range can be used. In the case of oral administration, a so-called drink can be added to a beverage.

The peptide according to the sixth invention of the present invention is a peptide having an amino acid sequence represented by SEQ ID NO: 19 in the sequence listing. Since the peptide has a function of suppressing allergy (allergy suppressing effect), it is useful as an allergy inhibitor and is applied to medicines, foods, and the like. For example, the peptide according to the sixth aspect of the present invention is blended as an active ingredient and applied to medicines, foods and the like such as allergic inhibitors. Of these, allergy inhibitors as medicines can be used for the treatment of allergic diseases such as atopic dermatitis, bronchial asthma, allergic rhinitis, etc .. The application of is also included in the category of the allergy suppressant of the present invention.

As in the case of the fat accumulation inhibitor, one or more amino acids in the amino acid sequence shown in SEQ ID NO: 19 are substituted or deleted, or one or more amino acids are inserted in the amino acid sequence. A peptide having an added or added amino acid sequence and having an allergy suppressing effect is also included in the scope of the peptide according to the sixth invention of the present invention. It is preferable that the amino acid sequence of such a peptide has 70% or more, more preferably 90% or more homology with the amino acid sequence represented by SEQ ID NO: 19. The allergy inhibitor as a medicament according to the sixth aspect of the present invention is preferably administered by a parenteral route such as intravenous injection, subcutaneous injection, intramuscular injection, or rectal administration, or orally. The dosage is appropriately determined based on the condition of the patient, the molecular weight of the active ingredient, and the like. Usually, in the case of parenteral administration, the body weight is preferably 1 kg and the daily dose is preferably about 0.1 mg to 0.1 mg. In the case of oral administration, the body weight is preferably about 1 kg, and about 0.1 to 10 mg per day. The allergy inhibitor comprising the peptide according to the sixth invention can be appropriately formulated by a conventional method.For example, a drug dissolved in physiological saline in a concentration range of S OmgZl SOO OmgZl can be used. Can be used. In the case of oral administration, a so-called drink can be added to a beverage. The peptide according to the seventh invention of the present invention is a peptide having an amino acid sequence represented by SEQ ID NO: 20, 21 or 22. Since the peptide has a function of lowering blood pressure (blood pressure lowering effect), it is useful as a blood pressure lowering agent, and is applied to medicines, foods and the like. For example, the above-mentioned peptide according to the seventh aspect of the present invention is blended as an active ingredient, and is applied to medicines, foods and the like such as antihypertensive agents. Among them, the antihypertensive agent as a medicament can be used for treatment and prevention of hypertension.

As in the case of the fat accumulation inhibitor, one or more amino acids in the amino acid sequence shown in SEQ ID NO: 20, 21, or 22 are replaced or deleted, or one or more amino acids are substituted in the amino acid sequence. A peptide having an amino acid sequence in which the amino acid is inserted or added and having a blood pressure lowering effect is also included in the scope of the peptide according to the seventh aspect of the present invention. The amino acid sequence of such a peptide preferably has 70% or more, more preferably 90% or more homology with the amino acid sequence shown in SEQ ID NO: 20, 21 or 22 <Seventh Invention The antihypertensive agent as a medicament according to the present invention is preferably administered by parenteral route such as intravenous injection, subcutaneous injection, intramuscular injection, rectal administration or oral administration. The dosage is determined appropriately based on the condition of the patient, the molecular weight of the active ingredient, and the like. In this case, the body weight is preferably about lkg, and about 0.01 mg to 1 mg per day, and for oral administration, about 1 kg, about 0.1 to 10 mg per day is preferable. In addition, the antihypertensive comprising the peptide according to the seventh aspect of the present invention can be appropriately formulated by a conventional method.For example, the antihypertensive was dissolved in physiological saline in a concentration range of 30 mg / l to 300 mg / l. Can be used. In the case of oral administration, a so-called drink can be added to a beverage.

The peptide according to the eighth invention of the present invention is a peptide having the amino acid sequence represented by SEQ ID NO: 23 or 24. Since the peptide has a function of relieving pain (analgesic effect), it is useful as an analgesic and is applied to medicines, foods and the like. For example, the peptide according to the eighth aspect of the present invention is blended as an active ingredient and applied to medicines such as analgesics, foods and the like. Of these, analgesics as medicines can be used for treatment of headache, menstrual pain and the like.

As in the case of the fat accumulation inhibitor, one or more amino acids in the amino acid sequence shown in SEQ ID NO: 23 or 24 are substituted or deleted, or one or more amino acids are added to the amino acid sequence. A peptide having an amino acid sequence into which is inserted or added and having an analgesic effect is also included in the scope of the peptide according to the eighth invention of the present invention. The amino acid sequence of such a peptide preferably has 70% or more, more preferably 90% or more homology with the amino acid sequence represented by SEQ ID NO: 23 or 24.

The analgesic as a medicament according to the eighth invention is preferably administered by a parenteral route such as intravenous injection, subcutaneous injection, intramuscular injection, rectal administration, or oral administration. The dosage is appropriately determined based on the condition of the patient, the molecular weight of the active ingredient, and the like.In general, for parenteral administration, the body weight is preferably 1 kg and the daily dose is preferably about 0.0 to 1 mg. In the case of administration, the body weight is preferably 1 kg, 0.1 mg per day; The analgesic comprising the peptide according to the eighth invention can be appropriately formulated by a conventional method. A solution dissolved in water at a concentration range of 30 mg / l to 300 Omg / 1 can be used. In the case of oral administration, a so-called drink can be added to a beverage.

The peptide according to the ninth invention of the present invention is a peptide having an amino acid sequence represented by SEQ ID NOS: 25, 26, 27, 28, 29, 30, 31 or 32. Since the peptide has a function of promoting central nervous system function (central nervous system function promoting effect), it is useful as a central nervous system function promoter and is applied to medicines, foods, and the like. For example, the above-mentioned peptide according to the ninth aspect of the present invention is blended as an active ingredient, and is applied to pharmaceuticals such as central nervous system function promoters, foods and the like. Among these drugs, central nervous system function promoters can be used to prevent cerebral nerve dysfunction due to cerebral ischemic injury or to improve cerebral nerve dysfunction (recovery treatment), etc. The therapeutic agent for improving cerebral nerve dysfunction and application as a drug for central nervous system are also included in the category of the central nervous system function promoter of the present invention.

In addition, as in the case of the fat accumulation inhibitor, one or more amino acids in the amino acid sequence shown in SEQ ID NO: 25, 26, 27, 28, 29, 30, 31 or 32 are the same. Peptides having an amino acid sequence in which one or more amino acids are substituted or deleted, or one or more amino acids are inserted or added to the amino acid sequence, and which have a central nervous system function promoting effect are also included in the present invention. Included in the range of peptides according to the nine inventions. The amino acid sequence of such a peptide is at least 70%, more preferably 90%, the amino acid sequence represented by SEQ ID NOS: 25, 26, 27, 28, 29, 30, 31 or 32. It is preferable to have the above homology.

The agent for promoting central nervous system function as a medicament according to the ninth invention is preferably administered by parenteral route such as intravenous injection, subcutaneous injection, intramuscular injection, or rectal administration, or orally. . The dosage is determined as appropriate based on the condition of the patient, the molecular weight of the active ingredient, and the like.In general, for parenteral administration, the body weight is 1 kg, and the dose is 0.01 mg to 1 mg per day. In the case of oral administration, the body weight is preferably 1 kg and about 0.1 mg to 10 mg per day. The central nervous system function promoter comprising the peptide according to the ninth invention can be appropriately formulated by a conventional method. For example, 30 mg / l to 300 mg Z 1 of physiological saline can be used. Those dissolved in the concentration range can be used. In the case of oral administration, a so-called drink can be added to a beverage.

The peptide having the amino acid sequence represented by SEQ ID NOS: 1 to 32 in the sequence listing according to the present invention can be easily synthesized by a well-known peptide chemical synthesis method using a commercially available peptide synthesizer. The synthesis method includes a solid phase method and a liquid phase method. The synthesized peptide is purified according to a usual method. Examples of the purification method include ion exchange chromatography, reverse phase liquid chromatography, affinity chromatography and the like. Further, the peptide of the present invention can also be produced by incorporating a gene corresponding to the amino acid sequence of the peptide of the present invention and an expression promoter into Escherichia coli, yeast and the like by using a gene modification technique. The obtained peptide is analyzed and confirmed with a mass spectrometer or a protein sequencer. Hereinafter, the present invention will be described specifically with reference to examples.

Example 1 Insulin production promoting action

(1) Synthesis of peptide

The peptide having the amino acid sequence represented by SEQ ID NO: 1 was synthesized, purified, and confirmed in the following manner by consignment to CSBIO LTD. (Ca1ifornia, U.S.A.). That is, it is synthesized by the solid phase method, the purity is assayed using reversed-phase liquid chromatography (Vy dac C18 column, trifluoroacetic acid Zacetonitrile solvent system), and the molecular weight of the product is analyzed using a mass spectrometer. It was confirmed.

(2) Promotion of insulin production by insulin-producing cells

HIT cells, which are hamster kidney cells that produce insulin (Manufactured by Dainippon Pharmaceutical Co., Ltd.) in RPMI 1640 medium containing 10% fetal bovine serum (source: Dainippon Pharmaceutical Co., Ltd.), and humidified in 5% carbon dioxide gas at 37 ^nC Nurtured. 1 × 10 ⁴ wells (we 11) were seeded on a 96-well culture plate by trypsin treatment, and when the culture became confluent, the medium was replaced with a serum-free F12 medium and cultured for 8 hours. Thereafter, the peptide having the amino acid sequence shown in SEQ ID NO: 1 of the present invention synthesized in (1) was dissolved in serum-free RPMI 1640 medium, and added to we11 while changing the dose of HIT cells. The culture was continued for another 12 hours. After the culture, the effect of the peptide on promoting the production of insulin by the cells was measured by insulin immunoassay, and the effect of promoting the production on the non-treated group was determined. In addition, the calculation of the insulin immunoassay and insulin production promotion rates was specifically performed as follows. According to the procedure of an insulin measurement kit commercially available from Shibayagi Co., Ltd., the cell culture solution supernatant was added to the anti-insulin antibody-fixed well and reacted with the anti-insulin antibody solution while changing the dose. For detection, biotin labeled with the antibody was reacted with streptavidin-conjugated peroxidase, and the color development by peroxidase was measured. Insulin concentration was calculated from a standard curve of insulin. The insulin production promotion rate was as follows when the control group without addition of the peptide was set to 100% and the insulin production promotion rate of the group to which the dose was changed was obtained. Table 1 shows the results.

(table 1 )

Peptide addition amount g / well) Insulin production promotion rate (%)

0

0. 01 1 01. 9

0.1

1 1 36. 7

10 141. 3 As is apparent from Table 1, it was confirmed that the peptide having the amino acid sequence shown in SEQ ID NO: 1 of the present invention acts on hamster-derived insulin-producing cells in a manner that promotes insulin production. Therefore, the peptide having the amino acid sequence shown in SEQ ID NO: 1 of the present invention promotes insulin production, has a function as an insulin production promoter, and is useful as a therapeutic agent for diabetes (insulin production promoter). It can be seen that It can also be seen that it can be used for foods that have an insulin production promoting function. Example 2 Gastric acid secretion inhibitory action

(1) Synthesis of peptide

In the same manner as in Example 1, a peptide having the amino acid sequence shown in SEQ ID NO: 2 was synthesized, purified, and confirmed.

(2) Suppression of gastric acid secretion in rats

The gastric acid secretion inhibitory effect was evaluated by using a rat (Wistar sp.) By combining a peptide having the amino acid sequence represented by SEQ ID NO: 2 of the present invention synthesized in (1) with gastrin that promotes gastric acid secretion in physiological saline. The dissolved solution was injected subcutaneously and evaluated by measuring gastric acid secretion 10 minutes later. Gastrin was administered to the peptide, and the peptide having the amino acid sequence shown in SEQ ID NO: 2 was administered to give 10 g Zkg. Gastric acid secretion was evaluated by fixing the rat to a fixator, inserting a probe into the stomach through the mouth, collecting gastric juice, and measuring the pH. The results are shown in Table 2 below. The control is a result of a control group to which the peptide was not administered.

(Table 2)

PH of collected gastric juice

Control 3.2

Administration group 4.7 As is clear from Table 2, it was confirmed that the peptide having the amino acid sequence shown in SEQ ID NO: 2 of the present invention acts on rats to inhibit gastric acid secretion. Therefore, the peptide of the present invention having the amino acid sequence represented by SEQ ID NO: 2 suppresses gastric acid secretion, has a function as a gastric acid secretion inhibitor, and is useful as a therapeutic agent for gastric ulcer and duodenal ulcer (gastric acid secretion inhibitor). You can see that there is. It can also be seen that it can be used for foods that have a gastric acid secretion inhibitory function. Example 3 Growth hormone production promoting action

(1) Synthesis of peptide

In the same manner as in Example 1, a peptide having the amino acid sequence shown in SEQ ID NO: 3 was synthesized, purified, and confirmed.

(2) Promotion of growth hormone production by growth hormone producing cells

Hamster-derived GH3 cells, which are pituitary cells that produce growth hormone (obtained from: IFO (Accession No. 5105)), and F12 medium containing 15% fetal bovine serum (obtained from Dainippon Japan) Pharmaceuticals) and cultivated in a 5% CO2 humidified 37 incubator. 1 x 10 ⁴ Z wells were seeded on a 96-well culture plate by trypsin treatment and confluent. The medium was replaced with a 15% serum F12 medium when cultivated for 12 hours, and then the peptide having the amino acid sequence shown in SEQ ID NO: 3 of the present invention synthesized in (1) was replaced with 1%. After dissolving in 5% serum F12 medium, the dose was changed and added to we11, and the culture was continued for another 3 days.After the culture, the effect of the peptide on promoting growth hormone production of cells by the growth hormone Imnoassay was examined. The production promoting effect on the untreated group was determined. Growth hormone immunoassay was performed by a standard sandwich ELISA method, in which the cell culture supernatant was added to the anti-growth hormone antibody-fixed well at varying doses and reacted at room temperature for 180 minutes. After washing, a peroxidase-labeled anti-growth hormone antibody was further added, and the mixture was allowed to react at room temperature for 60 minutes. It was measured by degree measurement. Growth hormone concentration was determined based on a standard curve obtained by performing the same sandwich ELISA using a known concentration of growth hormone. The growth hormone production promotion rate was as follows when the control group to which no peptide was added was set to 100%, and the growth hormone production promotion rate of the group to which the dose was changed was calculated. Table 3 shows the results.

(Table 3)

In Table 3,

(* 1) Peptide having the amino acid sequence shown in SEQ ID NO: 3, as is apparent from Table 3, the peptide having the amino acid sequence shown in SEQ ID NO: 3 of the present invention is a growth hormone-producing cell for growth hormone-producing cells. It was confirmed that it acts to promote production. Therefore, the peptide of the present invention having the amino acid sequence represented by SEQ ID NO: 3 promotes growth hormone production, has a function as a growth hormone production promoter, and is used as a therapeutic agent for dwarf disease (growth hormone production promotion). It is found to be useful as an agent. Also, it can be seen that it can be used for foods that have a growth hormone production promoting function. Example 4 Blood pressure lowering effect

(1) Synthesis of peptide

In the same manner as in Example 1, SEQ ID NOs: 4, 5, 6, 7, 8, 9, 10, A peptide having the amino acid sequence shown in 11 or 12 was synthesized, purified, and confirmed.

(2) Blood pressure lowering effect in rats

In a 10-week-old spontaneously hypertensive model rat (SHR, male), SEQ ID NO: 4, 5, 6, 7, 8, 9, 10, 10, 11 or 12 of the present invention synthesized in (1) was added. A peptide having the amino acid sequence shown was intraperitoneally administered to give 10 jug Z kg, and physiological saline was similarly administered as a control instead of the above peptide solution. The tail artery blood pressure before and 1 hour after administration was measured using a rat tail artery blood pressure / pulse meter (KN-210, manufactured by Natsume Seisakusho). Table 4 shows the results.

(Table 4)

In Table 4,

(* 1) peptide having the amino acid sequence shown in SEQ ID NO: 4 (* 2) peptide having the amino acid sequence shown in SEQ ID NO: 5 (* 3) peptide having the amino acid sequence of SEQ ID NO: 6

(* 4) a peptide having the amino acid sequence of SEQ ID NO: 7

(* 5) peptide having the amino acid sequence of SEQ ID NO: 8

(* 6) a peptide having the amino acid sequence of SEQ ID NO: 9

(* 7) Peptide having the amino acid sequence shown in SEQ ID NO: 10 (* 8) Peptide having the amino acid sequence shown in SEQ ID NO: 11 (* 9) Peptide having the amino acid sequence shown in SEQ ID NO: 12 Table As is clear from 4, it was confirmed that the peptide having the amino acid sequence of SEQ ID NOs: 4, 5, 6, 7, 8, 9, 10, 11, or 12 of the present invention has a blood pressure lowering effect. Was done. Therefore, the peptide of the present invention having the amino acid sequence shown in SEQ ID NOs: 4, 5, 6, 7, 8, 9, 10, 11, or 12 has a function as a hypotensive agent. It is found to be useful as a remedy for blood pressure (hypertensive agent). It can also be seen that it can be used for foods that have a blood pressure lowering function. Example 5 Fat accumulation inhibitory action

(1) Synthesis of peptide

In the same manner as in Example 1, peptides having the amino acid sequences shown in SEQ ID NOs: 13, 14, 15, 15, 16, 17 and 18 were synthesized, purified, and confirmed.

(2) Fat accumulation inhibitory action (1)

Adipocytes that accumulate fat were cultured in a 37 ° C. incubator with 5% carbon dioxide gas humidified using an RPM 1 1640 medium containing 10% fetal bovine serum (source: Dainippon Pharmaceutical). 1 × 10 ⁴ Z holes (we 11) were seeded on a 96-well culture plate, and when confluent, the medium was replaced with a serum-free F 12 medium and cultured for 8 hours. Thereafter, the peptide having the amino acid sequence shown in SEQ ID NOS: 13 and 14 of the present invention synthesized in (1) was dissolved in serum-free RPMI 11640 medium, and added to wel 1 while changing the dose. The culture was continued for another 24 hours. After the culture, the fat accumulation of the cells by the peptide was determined by the presence or absence of fat granules, The fat accumulation rate for the group was determined. The fat accumulation rate was determined by counting the number of fat accumulated cells in each group by microscopic observation, and expressed as a percentage of the number of fat accumulated cells in the control group to which the peptide was not added. Table 5 shows the results.

(Table 5)

In Table 5,

(* 1) peptide having the amino acid sequence shown in SEQ ID NO: 13 (* 2) peptide having the amino acid sequence shown in SEQ ID NO: 14 As is clear from Table 5, SEQ ID NOS: 13 and 1 of the present invention It was confirmed that the peptide having the amino acid sequence shown in 4 inhibits fat accumulation in cells and has a fat accumulation inhibitory action (function). Therefore, the peptides of the present invention having the amino acid sequences shown in SEQ ID NOS: 13 and 14 are useful as fat accumulation inhibitors, and are formulated as an active ingredient by using the peptide for hyperlipidemia as a medicament. It can be used for fat accumulation inhibitors such as anti-obesity agents, obesity treatment agents and obesity prevention agents, and foods having a function of inhibiting fat accumulation.

(3) Fat accumulation inhibitory action (2)

Rats (Wistar, male, 6 weeks old) were allowed to freely ingest a high-fat diet, and the amino acid sequence represented by SEQ ID NOS: 15, 16, 16, 17 and 18 of the present invention synthesized in the above (1) was obtained every day. 4 weeks after intraperitoneal administration of peptide having Immediately afterwards, blood was collected and the level of triglyceride (TG) in the blood was measured. Each peptide of the present invention was dissolved in physiological saline and injected into the abdominal cavity at a dose of 10 ag / kg. For the control group, physiological saline was similarly injected intraperitoneally. Table 6 shows the results.

(Table 6)

In Table 6,

(* 1) peptide having the amino acid sequence shown in SEQ ID NO: 15 (* 2) peptide having the amino acid sequence shown in SEQ ID NO: 16 (* 3) peptide having the amino acid sequence shown in SEQ ID NO: 17 (* 4) Peptide having the amino acid sequence shown in SEQ ID NO: 18 As is clear from Table 6, a peptide having the amino acid sequence shown in SEQ ID NOS: 15, 16, 17, and 18 of the present invention Was confirmed to have the function (function) of suppressing the increase of triglyceride in blood by a high-fat diet rat. Therefore, the peptide of the present invention having the amino acid sequence represented by SEQ ID NOS: 15, 16, 17, and 18 suppresses fat accumulation, is useful as a fat accumulation inhibitor, and It can be seen that it can be used as a medicament for hyperlipidemia as a medicament, an agent for treating fat accumulation, an agent for treating obesity, an agent for preventing obesity, and a food having an inhibitory function on fat accumulation. Example 6 Allergic inhibitory action

(1) Synthesis of peptide

In the same manner as in Example 1, a peptide having the amino acid sequence shown in SEQ ID NO: 19 was synthesized, purified, and confirmed.

(2) Allergy suppression

The inhibitory effect of histamine release is released simultaneously.) 3-Hexosaminidase activity was measured as an index. ⁵ X 1 0 5 pieces of RBL - 2 H 3 cells were seeded in each we 1 1 of the (purchased from Foundation for Human Science Research Resources Bank) a 4 8 we 1 1 culture plate, R PM I 1, including a 3% FBS and cultured for 24 hours at 3 7 ° C, 5% C0 2 under with 6 40 culture. The following reaction mixture (250 L) was added to the culture, and the mixture was reacted at 37 ° C for 1 hour. Thereafter, 100 L of extracellular solution was collected from each we11, and the remaining extracellular solution was removed. Using 250 L of 0.2% Triton X-1000 solution, the cells of each well 1 were lysed to give an intracellular solution, and IOOL was collected. ] 3—Hexosaminidase activity was determined by adding 5 mM p-nitrophenyl-2-acetaraido-2-deoxy-β-D-glucopyr anos ide (50 mM Add 400 L of citrate buffer solution to react, stop the reaction by adding 1 mL of 0.2 M daricin buffer (PH10.7), and absorb the resulting p-nitrophenol at an absorbance of 405 nm. Was measured. The ratio of β-hexosaminidase activity released outside the cells was calculated, and the degree of release inhibition relative to the control when the sample was added was calculated.

(Reaction mixture composition)

A peptide (0.1 mM to 10 mM) having the amino acid sequence shown in SEQ ID NO: 19 of the present invention synthesized in (1), a biotinylated mouse anti-DNPI gE antibody (3 g / mL) avidin (1 g / mL) their respective concentrated solutions were prepared of, releasing medium (1 1 6. 9 mM N a C to 5. 4mM KC l, 0. 8 mM Mg S 0 4, 5. 6 mM D one glucose, 2 5 mM HEPES, 2.O mM CaCl 1 mg / m 1 BSA, pH 7.7) Concentrations in parentheses per 1 ml To be added. The control without sample peptide is used as control. Table 7 shows the results.

(Table 7)

As is clear from Table 7, the peptide of the present invention having an amino acid sequence represented by SEQ ID NO: 19 has a high inhibitory rate of / 3-hexosaminidase release, which is an indicator of histamine release inhibition, and has an allergic inhibitory action ( Function). Therefore, the peptide of the present invention having the amino acid sequence represented by SEQ ID NO: 19 is useful as an allergy inhibitor, and is formulated by mixing the peptide as an active ingredient, as an allergy drug for medicine, a histamine release inhibitor, It can be seen that it can be used for allergy suppressants such as anti-inflammatory agents and foods with allergy suppression function. Example 7 Blood pressure lowering effect

(1) Synthesis of peptide

In the same manner as in Example 1, peptides having the amino acid sequences shown in SEQ ID NOs: 20, 21 and 22 were synthesized, purified, and confirmed. (2) Blood pressure lowering effect in rats

To a 10-week-old spontaneously hypertensive model rat (SHR, male), a peptide having the amino acid sequence shown in SEQ ID NOS: 20, 21 and 22 of the present invention synthesized in (1) was added to 1 0 zg / kg in the abdominal cavity. Saline was administered. The blood pressure of the tail artery was measured before and 1 hour after administration using a rat tail artery blood pressure / pulse meter (KN-210, manufactured by Natsume Seisakusho). Table 8 shows the results.

(Table 8)

In Table 8,

(* 1) peptide having the amino acid sequence shown in SEQ ID NO: 20 (* 2) peptide having the amino acid sequence shown in SEQ ID NO: 21 (* 3) peptide having the amino acid sequence shown in SEQ ID NO: 22 As apparent from Table 8, it was confirmed that the peptides of the present invention having the amino acid sequences shown in SEQ ID NOS: 20, 21, and 22 had a blood pressure lowering effect (function). Therefore, the peptides of the present invention having the amino acid sequences represented by SEQ ID NOs: 20, 21 and 22 are useful as antihypertensive agents, and are formulated by mixing the peptides as active ingredients and as antihypertensive agents as medicaments. It can also be seen that it can be used for foods that have a blood pressure lowering function. Example 8 Analgesic Action

(1) Synthesis of peptide

In the same manner as in Example 1, peptides having the amino acid sequences shown in SEQ ID NOS: 23 and 24 were synthesized, purified, and confirmed.

(2) analgesic effect The following experiment was performed using 10 rats (Wistar breed) per group. The peptide having the amino acid sequence shown in SEQ ID NOS: 23 and 24 of the present invention synthesized in (1) was dissolved in physiological saline, injected subcutaneously, and evaluated by a painless test after 10 minutes. The peptide of the present invention was administered so as to be 1 Oig Z kg, and only physiological saline was administered as a control. The analgesia test was performed by placing the rats on a heated hot plate (60 ° C) and measuring the time until jumping up. Table 9 shows the results.

(Table 9)

In Table 9,

(* 1) Peptide having the amino acid sequence shown in SEQ ID NO: 23 (* 2) Peptide having the amino acid sequence shown in SEQ ID NO: 24 As shown in Table 9, it is shown in SEQ ID NOs: 23 and 24 of the present invention. It was confirmed that the peptide having the amino acid sequence suppressed pain and had an analgesic effect (function). Therefore, the peptides of the present invention having the amino acid sequences shown in SEQ ID NOs: 23 and 24 are useful as analgesics, and the peptides are compounded as an active ingredient to provide an analgesic as a medicine and an analgesic function. It can be seen that it can be used for foods having Example 9 Central nervous system function promoting action

(1) Synthesis of peptide

In the same manner as in Example 1, SEQ ID NOS: 25, 26, 27, 28, 29, Peptides having the amino acid sequences shown in 30, 31 and 32 were synthesized, purified and confirmed.

(2) Central nervous system function promoting action

Prepare a 4-week-old Wistar rat (male). Use the Happa radial maze and train daily for one week to complete the spatial recognition of this maze. In other words, they place the bait on the eight ends of the maze, and learn to get the eight baits efficiently without entering the place where the bait was already taken by mistake until the bait has been completely taken. Thereafter, for 3 weeks, the administration group was added to SEQ ID NO: 25, 26, 27, 28, 29, 30, 30, 31 and 32 of the present invention synthesized at 10 mg / kg (1). The peptide having the amino acid sequence shown is injected intraperitoneally, and the control group is given physiological saline daily. At the end of the administration period, cerebral ischemia is created by holding the artery for 10 minutes, and the next day, the patient is placed in an eight-way maze to measure the degree of spatial recognition memory. Of the first eight attempts to reach the bait location at each aisle end, the number of correctly reached bait locations is referred to as the `` positive selection number ''. The number of times it reached was defined as the “number of errors” and counted. An increase in the number of positive selections for the control and / or a decrease in the number of errors indicate that the cerebral ischemia has an effect of alleviating the disorder or an early recovery from the disorder. The results are shown in Table 10.

(Table 10)

In Table 10,

(* 1) a peptide having the amino acid sequence shown in SEQ ID NO: 25 (* 2) a peptide having the amino acid sequence shown in SEQ ID NO: 26 (* 3) having the amino acid sequence shown in SEQ ID NO: 27 Peptide (* 4) Peptide having the amino acid sequence shown in SEQ ID NO: 28 (* 5) Peptide having the amino acid sequence shown in SEQ ID NO: 29 (* 6) Having the amino acid sequence shown in SEQ ID NO: 30 Peptide (* 7) Peptide having the amino acid sequence shown in SEQ ID NO: 31 (* 8) Peptide having the amino acid sequence shown in SEQ ID NO: 32 As is clear from Table 10, SEQ ID NO: 25, 26, 27, 28, 29, 30, 30, 31 and 32 reduce the damage caused by cerebral ischemia and recover from the damage early. However, it has been confirmed that it has a function to promote central nervous system function. Therefore, SEQ ID NOs: 25, 26, 27, 28, 29, 3 Peptides having the amino acid sequences represented by 0, 31 and 32 are useful as central nervous system function promoters, and are used as prophylactic and therapeutic agents for brain nerve dysfunction as pharmaceuticals by incorporating the peptides as active ingredients. It can be seen that it can be used for central nervous system function promoters such as therapeutic agents for improving cerebral nerve dysfunction, drugs for the central nervous system, cerebral nerve function protectants (drugs), and foods that have the function of promoting central nervous system function. Industrial applicability

As described in detail above, according to the present invention, a peptide particularly useful as a medicine or food can be obtained. Peptides having the amino acid sequences represented by SEQ ID NOs: 1 to 32 in the sequence listing of the present invention are particularly useful as insulin production promoters, gastric acid secretion inhibitors, growth hormone production promoters, hypotensive agents, and fat accumulation inhibitors. , An allergy inhibitor, an analgesic, a central nervous system function promoter, etc., and a novel amino acid sequence represented by SEQ ID NOS: 1 to 32 in the sequence listing of the present invention, Drugs, foods, etc. can be obtained.

Claims

The scope of the claims

I. a peptide having the amino acid sequence represented by SEQ ID NO: 1 in the sequence listing, or one or more amino acids in the amino acid sequence substituted or deleted, or one or more amino acids in the amino acid sequence A peptide having an amino acid sequence in which an amino acid sequence is inserted or added. A peptide having an insulin production promoting effect.

2. The peptide according to claim 1, comprising a peptide having the amino acid sequence represented by SEQ ID NO: 1 in the sequence listing as an active ingredient.

3. An insulin production promoter comprising the peptide according to claim 1 or 2.

4. A medicine or food containing the peptide according to claim 1 or 2 as an active ingredient.

5. The medicament or food according to claim 4, which is an insulin production promoter.

6. A peptide having the amino acid sequence represented by SEQ ID NO: 2 in the sequence listing, or one or more amino acids in the amino acid sequence are substituted or deleted, or one or more amino acids in the amino acid sequence A peptide having an inserted or added amino acid sequence, which has an effect of suppressing gastric acid secretion.

7. The peptide according to claim 6, comprising a peptide having an amino acid sequence represented by SEQ ID NO: 2 in the sequence listing as an active ingredient.

8. A gastric acid secretion inhibitor comprising the peptide according to claim 6 or 7.

9. A medicine or food containing the peptide according to claim 6 or 7 as an active ingredient.

10. The medicament or food according to claim 9, which is a gastric acid secretion inhibitor.

II. A peptide having an amino acid sequence represented by SEQ ID NO: 3 in the sequence listing, or one or more amino acids in the amino acid sequence are substituted or deleted, or one or more amino acids in the amino acid sequence A peptide having an amino acid sequence in which is inserted or added, wherein the peptide has a growth hormone production promoting effect.

12. The peptide according to claim 11, comprising a peptide having an amino acid sequence represented by SEQ ID NO: 3 in the sequence listing as an active ingredient.

1 3. A growth hormone production promoter comprising the peptide according to claim 11 or 12.

1 4. A medicine or food containing the peptide according to claim 11 or 12 as an active ingredient.

15. The drug or food according to claim 14, which is a growth hormone production promoter.

1 6. Peptide having the amino acid sequence represented by SEQ ID NOs: 4, 5, 6, 7, 8, 9, 10, 11, or 12, or one or more amino acids in the amino acid sequence are substituted A peptide having an amino acid sequence in which one or more amino acids are inserted or added to the amino acid sequence, wherein the peptide has a blood pressure lowering effect.

1 7.SEQ ID NO: 4, 5, 6, 7, 8, 9, 10 or 11, or

17. The peptide according to claim 16, wherein the peptide having the amino acid sequence represented by 12 is an active ingredient.

18. An antihypertensive comprising the peptide according to claim 16 or 17.

1 9. A medicine or food containing the peptide according to claim 16 or 17 as an active ingredient.

20. The medicament or food according to claim 19, which is a hypotensive agent.

2 1. A peptide having an amino acid sequence represented by SEQ ID NO: 13, 14, 15, 15, 16, 17, or 18, or one or more amino acids in the amino acid sequence are substituted or substituted. A peptide having an amino acid sequence deleted or having one or more amino acids inserted or added to the amino acid sequence, the peptide having an effect of suppressing fat accumulation.

22. The method according to claim 21, wherein a peptide having an amino acid sequence represented by SEQ ID NOS: 13, 14, 15, 16, 16, 17 or 18 in the sequence listing is used as an active ingredient. Puchido.

23. A fat accumulation inhibitor comprising the peptide according to claim 21 or 22.

24. A medicine or food containing the peptide according to claim 21 or 22 as an active ingredient.

25. The medicament or food according to claim 24, which is a fat accumulation inhibitor.

26. A peptide having the amino acid sequence of SEQ ID NO: 19 in the sequence listing, or one or more amino acids in the amino acid sequence are substituted or deleted, or one or more amino acids are added to the amino acid sequence A peptide having an amino acid sequence to which an acid has been inserted or added, and which has an allergy suppressing effect.

27. The peptide according to claim 26, comprising a peptide having an amino acid sequence represented by SEQ ID NO: 19 in the sequence listing as an active ingredient.

28. An allergy inhibitor comprising the peptide according to claim 26 or 27.

29. A medicament or food containing the peptide according to claim 26 or 27 as an active ingredient.

30. The medicament or food according to claim 29, which is an allergy suppressant.

31. A peptide having the amino acid sequence represented by SEQ ID NO: 20, 21, or 22, or one or more amino acids in the amino acid sequence are substituted or deleted, or Alternatively, a peptide having an amino acid sequence in which a plurality of amino acids have been inserted or added, and which has a blood pressure lowering effect.

32. The peptide according to claim 31, comprising a peptide having an amino acid sequence represented by SEQ ID NO: 20, 21 or 22 as an active ingredient.

33. Blood pressure reduction comprising the peptide according to claim 31 or 32. laxative.

3 4. A medicament or food containing the peptide according to claim 31 or 32 as an active ingredient.

3 5. The medicament or food according to claim 34, which is a hypotensive agent.

3 6. A peptide having the amino acid sequence represented by SEQ ID NO: 23 or 24 in the sequence listing, or one or more amino acids in the amino acid sequence are substituted or deleted, or one or more amino acids are substituted in the amino acid sequence. A peptide having an amino acid sequence in which a plurality of amino acids are inserted or added, wherein the peptide has an analgesic effect.

3 7.The peptide according to claim 36, wherein the peptide having an amino acid sequence represented by SEQ ID NO: 23 or 24 in the sequence listing is used as an active ingredient.

38. An analgesic comprising the peptide according to claim 36 or 37.

3 9. A medicine or food containing the peptide according to claim 36 or 37 as an active ingredient.

40. The medicament or food according to claim 39, which is an analgesic.

4 1. A peptide having an amino acid sequence represented by SEQ ID NO: 25, 26, 27, 28, 29, 30, 31 or 32 in the sequence listing, or a peptide in the amino acid sequence A peptide having an amino acid sequence in which one or more amino acids have been substituted or deleted, or one or more amino acids have been added or added to the amino acid sequence, and have a central nervous system function promoting effect Peptide.

42. The method according to claim 41, wherein the peptide having an amino acid sequence represented by SEQ ID NO: 25, 26, 27, 28, 29, 30, 31 or 32 in the sequence listing is used as an active ingredient. Item.

43. A central nervous system function promoter comprising the peptide according to claim 41 or 42.

44. A medicine or food containing the peptide according to claim 41 or 42 as an active ingredient.

4 5. The medicament or food according to claim 44, which is a central nervous system function promoter.