JP2001335596A - New peptide and its medical use - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a new peptide having a quite different mechanism of action from conventional agents, usable for hypotensive agent, an analgesic, a somatotrophic hormone production inhibitor, an adipopexis inhibitor, a stimulant agent of calcium concentration in blood, a hyperacid inhibitor, a prostaglandin E2 production promoter, an osteoblastic growth promoter and a somatotrophic hormone production promoter. SOLUTION: The hypotensive agent, the analgesic, the somatotrophic hormone production inhibitor, ht adipopexis inhibitor, the stimulant agent of calcium concentration in blood, the hyperacid inhibitor, the prostaglandin E2 production promoter, the osteoblastic growth promoter and the somatotrophic hormone production promoter composed of a peptide having a specific amino acid sequence are provided.

Description

DETAILED DESCRIPTION OF THE INVENTION TECHNICAL FIELD OF THE INVENTION

[0001] The present invention relates to a novel peptide and its pharmaceutical use.

[0002]

2. Description of the Related Art Conventionally, various drugs have been used as antihypertensives, analgesics, gastric acid secretion inhibitors, osteoporosis drugs, dwarfism drugs and the like.

[0003]

It is needless to say that if a novel drug having excellent pharmacological effects is provided for a certain disease, it is advantageous for the treatment of the disease.

It is an object of the present invention to exhibit an excellent pharmacological effect, a mechanism of action which is completely different from that of conventional drugs, a blood pressure suppressing effect, an analgesic effect, a growth hormone production inhibiting effect, an adipocyte fat accumulation inhibiting effect, Gastric acid secretion inhibitory effect, blood calcium concentration increasing effect, gastric acid secretion inhibitory, prostaglandin E2
An object of the present invention is to provide novel compounds having a production promoting effect, an osteoblast proliferation promoting effect, or a growth hormone production promoting effect, and their pharmaceutical uses.

[0005]

Means for Solving the Problems As a result of intensive studies, the present inventors have found that a peptide having a specific amino acid sequence has an excellent blood pressure-suppressing effect, an analgesic effect, a growth hormone production inhibitory effect, and an adipocyte fat accumulation inhibitory effect. , Gastric acid secretion inhibitory effect,
The present inventors have found that they have an effect of increasing blood calcium concentration, suppress gastric acid secretion, promote prostaglandin E2 production, promote osteoblast proliferation or promote growth hormone production, and completed the present invention.

[0006] That is, the present invention relates to SEQ ID NO: 1 in the sequence listing.
Or a peptide having the amino acid sequence represented by 2, or having an amino acid sequence in which one or more amino acids in the amino acid sequence have been substituted or deleted, or one or more amino acids have been inserted or added to the amino acid sequence. A peptide having a blood pressure suppressing effect and a use thereof as a blood pressure suppressing agent are provided.

[0007] The present invention also relates to a peptide having the amino acid sequence represented by SEQ ID NO: 3 or 4 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. Alternatively, the present invention provides a peptide having an amino acid sequence in which a plurality of amino acids are inserted or added and having an analgesic effect, and its use as an analgesic.

Further, the present invention relates to a peptide having the amino acid sequence represented by SEQ ID NO: 5 in the sequence listing, or wherein 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. The present invention provides a peptide having an amino acid sequence having an amino acid inserted or added therein, which has a growth hormone production inhibitory effect, and its use as a growth hormone production inhibitor.

Further, the present invention relates to a peptide having the amino acid sequence represented by SEQ ID NO: 6 in the sequence listing, or wherein 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. The present invention provides a peptide having an amino acid sequence in which an amino acid is inserted or added, the peptide having an adipocyte fat accumulation inhibitory effect, and its use as a fat accumulation inhibitor.

Further, the present invention relates to a peptide having the amino acid sequence represented by SEQ ID NO: 7 or 8 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. Alternatively, the present invention provides a peptide having an amino acid sequence in which a plurality of amino acids are inserted or added and having a blood calcium concentration increasing effect, and use of the peptide as a blood calcium concentration increasing agent.

Furthermore, the present invention relates to a peptide having the amino acid sequence represented by SEQ ID NO: 9 in the sequence listing, or wherein 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. The present invention provides a peptide having an amino acid sequence in which the amino acid is inserted or added and having a gastric acid secretion inhibitory effect, and its use as a gastric acid secretion inhibitor.

Furthermore, the present invention relates to
Or a peptide having the amino acid sequence represented by 11, or having an amino acid sequence in which one or more amino acids in the amino acid sequence have been substituted or deleted, or one or more amino acids have been inserted or added to the amino acid sequence. Prostaglandin E2 which is a peptide
A peptide having a production promoting effect and its use as a prostaglandin E2 production promotion are provided.

Furthermore, the present invention relates to the present invention
A peptide having the amino acid sequence represented by 2, 13, 14 or 15, or substitution or deletion of one or more amino acids in the amino acid sequence, or insertion or addition of one or more amino acids in the amino acid sequence The present invention provides a peptide having an amino acid sequence, which has an osteoblast proliferation promoting effect, and its use as an osteoblast proliferation promoter.

Furthermore, the present invention relates to the present invention
A peptide having an amino acid sequence represented by 6, 17, 18, 19, 20 or 21, or substitution or deletion of one or more amino acids in the amino acid sequence, or insertion of one or more amino acids in the amino acid sequence A peptide having an added or added amino acid sequence and having a growth hormone production promoting effect, and its use as a growth hormone production promoter.

[0015]

BEST MODE FOR CARRYING OUT THE INVENTION The first invention of the present application relates to a peptide having a blood pressure suppressing effect and a blood pressure suppressing agent containing the peptide as an active ingredient. Since the blood pressure inhibitor of the present invention has an effect of suppressing blood pressure, it can be used for treating or preventing hypertension. The peptide of the present invention having a blood pressure suppressing effect is a peptide having an amino acid sequence represented by SEQ ID NO: 1 or 2 in the sequence listing.

In general, a peptide having a physiological activity has a small number of amino acid sequences substituted or deleted, or a small number of amino acid sequences inserted or added to the amino acid sequence. Even
It is well known to those skilled in the art that the physiological activity may be maintained. Therefore, SEQ ID NO: 1 or 2
A peptide having an amino acid sequence in which one or more amino acids in the amino acid sequence shown in the above are substituted or deleted, or one or more amino acids are inserted or added to the amino acid sequence, and has a blood pressure suppressing effect. Peptides are also included in the scope of the present invention. Here, “plurality” is preferably 6 or less in the case of SEQ ID NO: 1, more preferably 2 or less, and 9 in the case of SEQ ID NO: 2.
Or less, more preferably 3 or less.
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 shown in SEQ ID NO: 1 or 2.

The blood pressure suppressing agent of the present 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.
The dose is preferably about 1 mg to 0.01 mg per day, and in the case of oral administration, the weight is preferably 1 kg per day and about 10 mg to 0.1 mg per day. The blood pressure suppressant can be appropriately formulated by a conventional method. For example, 30 mg / l of physiological saline is added.
What was dissolved in the concentration range of ３3000 mg / l can be used. In the case of oral administration, a so-called drink can be added to a beverage.

The second invention of the present application relates to a peptide having an analgesic effect and an analgesic containing the peptide as an active ingredient. The peptide of the present invention having an analgesic effect is a peptide having an amino acid sequence represented by SEQ ID NO: 3 or 4 in the sequence listing.

In general, a peptide having a physiological activity has a small number of amino acid sequences substituted or deleted, or a small number of amino acid sequences inserted or added to the amino acid sequence. Even
It is well known to those skilled in the art that the physiological activity may be maintained. Therefore, SEQ ID NO: 3 or 4
A peptide having an analgesic effect, wherein the peptide has an amino acid sequence in which one or more amino acids in the amino acid sequence shown in the above are substituted or deleted, or one or more amino acids are inserted or added to the amino acid sequence, Are also included in the scope of the present invention. Here, “plurality” is preferably 4 or less, more preferably 2 or less in the case of SEQ ID NO: 3, and 6 or less, more preferably 2 or less in the case of SEQ ID NO: 4. 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: 3 or 4.

The analgesic of the present invention can be used for intravenous injection, subcutaneous injection,
It is preferable to administer by parenteral route such as 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. Usually, in the case of parenteral administration, the body weight is preferably 1 kg, about 1 mg to 0.01 mg per administration, and in the case of oral administration, The weight is preferably about 10 mg to 0.1 mg per 1 kg body weight. The analgesic can be appropriately formulated by a conventional method. For example, 30 mg / l to 3000 can be added to physiological saline.
Those dissolved in the concentration range of mg / l can be used. In the case of oral administration, a so-called drink can be added to a beverage.

[0021] The third invention of the present application relates to a peptide having a growth hormone production inhibitory effect and a growth hormone production inhibitor containing the peptide as an active ingredient. Since the growth hormone production inhibitor of the present invention inhibits growth hormone production, it can be used for treating or preventing giantosis or the like. The peptide of the present invention having a growth hormone production inhibitory effect is a peptide having an amino acid sequence represented by SEQ ID NO: 5 in the sequence listing.

In general, a peptide having a physiological activity has a small number of amino acid sequences substituted or deleted, or a small number of amino acid sequences inserted or added to the amino acid sequence. Even
It is well known to those skilled in the art that the physiological activity may be maintained. Accordingly, a peptide having an amino acid sequence in which one or more amino acids in the amino acid sequence shown in SEQ ID NO: 5 have been substituted or deleted, or one or more amino acids have been inserted or added in the amino acid sequence. Peptides having a growth hormone production inhibitory effect are also included in the scope of the present invention. Here, the “plurality” is preferably 8 or less, more preferably 3 or less. 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: 5.

The growth hormone production inhibitor of the present invention is preferably administered by a parenteral route such as intravenous injection, subcutaneous injection, intramuscular injection, rectal administration or oral administration. In addition, the dose 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, about 1 mg to 0.01 mg per day,
In the case of oral administration, 1 kg body weight, 10 mg per day
About 0.1 mg is preferable. The growth hormone production inhibitor can be appropriately formulated by a conventional method, and for example, a solution dissolved in physiological saline in a concentration range of 30 mg / l to 3000 mg / l can be used. In the case of oral administration, a so-called drink can be added to a beverage.

[0024] The fourth invention of the present application relates to a peptide having an effect of inhibiting fat accumulation in fat cells and a fat accumulation inhibitor containing the peptide as an active ingredient. Since the fat accumulation inhibitor of the present invention inhibits fat accumulation by fat cells,
It can be used for treatment or prevention of obesity and the like. The peptide of the present invention having an effect of inhibiting fat accumulation in adipocytes is a peptide having an amino acid sequence represented by SEQ ID NO: 6 in the sequence listing.

Generally, a peptide having a physiological activity has a small number of amino acid sequences substituted or deleted, or a small number of amino acid sequences inserted or added to the amino acid sequence. Even
It is well known to those skilled in the art that the physiological activity may be maintained. Therefore, a peptide having an amino acid sequence in which one or more amino acids in the amino acid sequence represented by SEQ ID NO: 6 have been substituted or deleted, or one or more amino acids have been inserted or added to the amino acid sequence. Peptides having a fat accumulation inhibiting effect are also included in the scope of the present invention. Here, the “plurality” is preferably three or less. The amino acid sequence of such a peptide corresponds to the amino acid sequence of SEQ ID NO: 6 and 70
%, More preferably 90% or more.

The fat accumulation inhibitor of the present invention is preferably administered by a parenteral route such as intravenous injection, subcutaneous injection, intramuscular injection, rectal administration or oral administration. The dose is appropriately determined based on the condition of the patient, the molecular weight of the active ingredient, and the like.
About 1 mg to 0.01 mg per day is preferable, and in the case of oral administration, the body weight is 1 kg and 10 mg to 0.1 mg per day.
The degree is preferred. The fat accumulation inhibitor can be appropriately formulated according to a conventional method.
Those dissolved in the concentration range of g / l to 3000 mg / l can be used. In the case of oral administration, a so-called drink can be added to a beverage.

The fifth invention of the present application relates to a peptide having an effect of increasing blood calcium concentration and a blood calcium concentration increasing agent containing the peptide as an active ingredient. Since the blood calcium concentration increasing agent of the present invention has an effect of increasing blood calcium concentration, it can be used for treating or preventing hypocalcemia and the like. The peptide of the present invention having the effect of increasing blood calcium concentration is a peptide having an amino acid sequence represented by SEQ ID NO: 7 or 8 in the sequence listing.

In general, a peptide having a physiological activity has a small number of amino acid sequences substituted or deleted, or a small number of amino acid sequences inserted or added to the amino acid sequence. Even
It is well known to those skilled in the art that the physiological activity may be maintained. Therefore, SEQ ID NO: 7 or 8
A peptide having an amino acid sequence in which one or more amino acids in the amino acid sequence shown in the above are substituted or deleted, or one or more amino acids are inserted or added to the amino acid sequence, and the blood calcium concentration is increased. Peptides having an effect are also included in the scope of the present invention.
Here, “plurality” is preferably 2 or less in the case of SEQ ID NO: 7, and is preferably 4 or less, more preferably 2 or less in the case of SEQ ID NO: 8. 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: 7 or 8.

The blood calcium concentration-increasing agent of the present invention is preferably administered by a parenteral route such as intravenous injection, subcutaneous injection, intramuscular injection, rectal administration, or oral administration.
In addition, the dose 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, about 1 mg to 0.01 mg per day, and in the case of oral administration, Is 1kg body weight, 10m per day
g to about 0.1 mg is preferred. The blood calcium concentration increasing agent can be appropriately formulated by a conventional method, and for example, a solution dissolved in physiological saline in a concentration range of 30 mg / l to 3000 mg / l can be used. In the case of oral administration, a so-called drink can be added to a beverage.

The sixth invention of the present application relates to a peptide having a gastric acid secretion inhibitory effect and a gastric acid secretion inhibitor containing the peptide as an active ingredient. Gastric acid secretion inhibitor of the present invention,
Since it suppresses gastric acid secretion, it can be used for treating or preventing gastric ulcer or duodenal ulcer. The peptide of the present invention having a gastric acid secretion inhibitory effect is represented by SEQ ID NO: 9 in the sequence listing.
Is a peptide having an amino acid sequence represented by

In general, a peptide having a physiological activity has a small number of amino acid sequences substituted or deleted, or a small number of amino acid sequences inserted or added to the amino acid sequence. Even
It is well known to those skilled in the art that the physiological activity may be maintained. Therefore, a peptide having an amino acid sequence in which one or more amino acids in the amino acid sequence shown in SEQ ID NO: 9 have been substituted or deleted, or one or more amino acids have been inserted or added to the amino acid sequence. Peptides having a gastric acid secretion inhibitory effect are also included in the scope of the present invention. Here, the “plurality” is preferably four or less, more preferably two or less. 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: 9.

The gastric acid secretion inhibitor of the present invention is preferably administered by a parenteral route such as intravenous injection, subcutaneous injection, intramuscular injection, rectal administration or oral administration. The dose is appropriately determined based on the condition of the patient, the molecular weight of the active ingredient, and the like.
About 1 mg to 0.01 mg per day is preferable, and in the case of oral administration, the body weight is 1 kg and 10 mg to 0.1 mg per day.
The degree is preferred. In addition, the gastric acid secretion inhibitor can be appropriately formulated by a conventional method.
Those dissolved in the concentration range of g / l to 3000 mg / l can be used. In the case of oral administration, a so-called drink can be added to a beverage.

The seventh invention of the present application is directed to a prostaglandin E
Having an effect of promoting production of Prostaglandin 2, and prostaglandin E2 containing the peptide as an active ingredient
It relates to a production promoter. Prostaglandin E2 of the present invention
The production promoter promotes production of prostaglandin E2. Prostaglandin E2 is known to have various physiological activities, in particular, a blood pressure lowering effect and a vasodilatory effect. Therefore, the prostaglandin E2 production promoter of the present invention can be used for treating or preventing hypertension and the like. In addition, since the physiological action of prostaglandin E2 is known in addition to the blood pressure lowering action and the vasodilatory action, it is effective against other diseases that can be treated or prevented by promoting the production of prostaglandin E2. It is also useful for treatment or prevention. The peptide of the present invention having a prostaglandin E2 production promoting effect is a peptide having an amino acid sequence represented by SEQ ID NO: 10 or 11 in the sequence listing.

In general, a peptide having a physiological activity has a small number of amino acid sequences substituted or deleted, or a small number of amino acid sequences inserted or added to the amino acid sequence. Even
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: 10 or 11 are substituted or deleted, or
Alternatively, a peptide having an amino acid sequence in which a plurality of amino acids are inserted or added and having a prostaglandin E2 production promoting effect is also included in the scope of the present invention. Here, “plurality” refers to SEQ ID NO: 10
Is preferably 5 or less, more preferably 2 or less, and in the case of SEQ ID NO: 11, 4 or less is preferable,
More preferably, the number is two or less. 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: 10 or 11.

The prostaglandin E2 production promoter of the present invention is preferably administered by a parenteral route such as intravenous injection, subcutaneous injection, intramuscular injection, rectal administration or oral administration. In addition, the dose 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, about 1 mg to 0.01 mg per day, and in the case of oral administration, Is preferably about 10 mg to 0.1 mg per body weight per day. In addition, the prostaglandin E2 production promoter can be appropriately formulated by a conventional method.
Those dissolved in a concentration range of 0 mg / l can be used. In the case of oral administration, a so-called drink can be added to a beverage.

The eighth invention of the present application relates to a peptide having an effect of promoting osteoblast proliferation and an osteoblast proliferation promoter containing the peptide as an active ingredient. Since the osteoblast proliferation promoter of the present invention has an effect of promoting osteoblast proliferation, it can be used for treatment or prevention of osteoporosis and the like. The peptides of the present invention having the effect of promoting the growth of osteoblasts are represented by SEQ ID NOs: 12, 13, 1 in the sequence listing.
A peptide having the amino acid sequence represented by 4 or 15.

In general, a peptide having a physiological activity has a small number of amino acid sequences substituted or deleted, or a small number of amino acid sequences inserted or added to the amino acid sequence. Even
It is well known to those skilled in the art that the physiological activity may be maintained. Therefore, SEQ ID NO: 12, 1
A peptide having an amino acid sequence in which one or more amino acids in the amino acid sequence shown in 3, 14, or 15 have been substituted or deleted, or one or more amino acids have been inserted or added to the amino acid sequence; Peptides having an effect of promoting osteoblast proliferation are also included in the scope of the present invention. Here, the term “plurality” is preferably 5 or less, more preferably 2 or less, in the case of SEQ ID NO: 12, and preferably 11 or less, more preferably 4 or less in the case of SEQ ID NO: 13. In the case of SEQ ID NO: 14, the number is preferably 5 or less, more preferably 2 or less.
Or less, and in the case of SEQ ID NO: 15, the number is preferably 5 or less, more preferably 2 or less. 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 shown in SEQ ID NO: 12, 13, 14, or 15.

The osteoblast proliferation promoter of the present invention is preferably administered by a parenteral route such as intravenous injection, subcutaneous injection, intramuscular injection, rectal administration, or oral administration. In addition, the dose 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, about 1 mg to 0.01 mg per day,
In the case of oral administration, 1 kg body weight, 10 mg per day
About 0.1 mg is preferable. The osteoblast proliferation promoter can be appropriately formulated by a conventional method. For example, an agent which is dissolved in physiological saline in a concentration range of 30 mg / l to 3000 mg / l can be used. In the case of oral administration, a so-called drink can be added to a beverage.

The ninth invention of the present application relates to a peptide having an effect of promoting the production of growth hormone and a growth hormone production accelerator containing the peptide as an active ingredient.
Since the growth hormone production promoter of the present invention has the effect of promoting the production of growth hormone, it can be used for treating or preventing dwarfism and the like. The peptide of the present invention having the effect of promoting the production of growth hormone is a peptide having an amino acid sequence represented by SEQ ID NO: 16, 17, 18, 19, 20, or 21 in the sequence listing.

In general, a peptide having a physiological activity has a small number of amino acid sequences substituted or deleted, or a small number of amino acid sequences inserted or added to the amino acid sequence. Even
It is well known to those skilled in the art that the physiological activity may be maintained. Therefore, SEQ ID NO: 16, 1
Having an amino acid sequence in which one or more amino acids in the amino acid sequence shown in 7, 18, 19, 20 or 21 are substituted or deleted, or one or more amino acids are inserted or added to the amino acid sequence Peptides having the effect of promoting the production of growth hormone are also included in the scope of the present invention. Here, “plurality” is preferably 3 or less in the case of SEQ ID NOs: 16 and 17, 2 or less in the case of SEQ ID NO: 18, and “plurality” is not preferred in the case of SEQ ID NO: 19. In the case of No. 20, the number is preferably 3 or less;
In this case, the number is preferably 10 or less, more preferably 4 or less. 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: 16, 17, 18, 19, 20 or 21.

The growth hormone production-promoting agent of the present invention is preferably administered by a parenteral route such as intravenous injection, subcutaneous injection, intramuscular injection, rectal administration or oral administration. In addition, the dose 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, about 1 mg to 0.01 mg per day,
In the case of oral administration, 1 kg body weight, 10 mg per day
About 0.1 mg is preferable. The growth hormone production promoter can be appropriately formulated by a conventional method, and for example, a solution dissolved in physiological saline in a concentration range of 30 mg / l to 3000 mg / l can be used. In the case of oral administration, a so-called drink can be added to a beverage.

[0042]

DESCRIPTION OF THE PREFERRED EMBODIMENTS The present invention will be described below more specifically based on embodiments. However, the present invention is not limited to the following examples.

Example 1 Blood Pressure Inhibitor (1) Synthesis of Peptide Peptides having the amino acid sequences shown in SEQ ID NOs: 1 and 2 were synthesized using a commercially available peptide synthesizer.

(2) Blood Pressure Suppressing Effect in Rats The blood pressure suppressing effect was measured in rats (SHR, 10 animals per group, body weight 25
0 g to 400 g, average body weight 300 g), the peptide produced in (1) was intraperitoneally administered, and the change over time in blood pressure 2 hours after administration was evaluated. The specific composition of the administered composition was obtained by dissolving the peptide prepared in (1) at a concentration of 3 μg / ml in physiological saline, and 0.8 to 1.3 ml of the composition was intraperitoneally administered. Blood pressure was measured in the tail artery, and the average value measured five times with a KN-210 rat tail artery and a pulse meter (Natsume Seisakusho, Tokyo, Japan) was used as the blood pressure value. FIG. 1 shows a change in blood pressure over time between the control group to which water containing no this substance was administered and the administration group.

As is clear from FIG. 1, the effect of the blood pressure suppressant of the present invention on blood pressure in rats was confirmed. Therefore, the peptide is considered to be linked to suppression of blood pressure also in humans, and is useful for treatment and prevention of hypertension and the like.

Example 2 Analgesic (1) Synthesis of Peptide A peptide having the amino acid sequence shown in SEQ ID NO: 3 or 4 was synthesized using a commercially available peptide synthesizer.

(2) Rats (Wistar species)
Was used as 10 animals per group. A solution prepared by dissolving the peptide synthesized in (1) in physiological saline was injected subcutaneously, and evaluated by a painless test 10 minutes later. Gastrin was administered at 4 μg / kg, and the peptide of the present invention was administered at 10 μg / kg. The painless test was performed on a hot plate (60
° C), and the time to jump up was measured. The results are shown in Table 1 below.

[0048]

[Table 1] Table 1

As is evident from Table 1, the above-mentioned peptides searched by the method of the present invention were confirmed to have an analgesic effect on rats. Therefore, the present peptide is useful as an analgesic.

Example 3 Growth Hormone Production Inhibitor (1) Synthesis of Peptide A peptide having the amino acid sequence of SEQ ID NO: 5 was synthesized using a commercially available peptide synthesizer.

(2) Inhibition of Growth Hormone Production by Growth Hormone-Producing Cells Hamster-derived GH3 cells, which are pituitary cells that produce growth hormone (obtained from ATCC), are cultured in F12 medium containing 15% fetal bovine serum (obtained from: (Nippon Pharmaceutical Co., Ltd.) and grown in a 5% CO 2 humidified 37 ° C. incubator. 1x10 ⁴ cells / well were seeded on a 96-well culture plate by trypsin treatment, and when confluent, the medium was reduced to 15%.
The medium was replaced with a serum F12 medium and cultured for 12 hours. Then (1)
Was dissolved in 15% serum F12 medium, added to the wells while changing the dose, and the culture was continued for 3 days. After the culture, the inhibitory effect of the peptide on the growth hormone production of the cells was measured by a growth hormone immunoassay, and the production promotion effect on the non-treated group was determined. The growth hormone immunoassay and the calculation of the growth hormone production inhibition rate were specifically performed as follows.
The cell culture supernatant was added to the wells on which the anti-growth hormone antibody was fixed while changing the dose, and reacted with the anti-growth hormone antibody solution. The detection was carried out by measuring the color of peroxidase labeled on the antibody. The growth hormone concentration was calculated from a growth hormone standard curve. The growth hormone production inhibition rate was as follows when the control group to which the substance was not added was taken as 100%, and the growth hormone production inhibition rate of the group to which the dose was changed was calculated. Table 2 shows the results.

[0052]

[Table 2] Table 2

As is evident from Table 2, it was confirmed that the above-mentioned peptides searched by the method of the present invention act on growth hormone-producing cells in a manner inhibiting growth hormone production. Therefore, the present peptide is considered to be linked to growth inhibition, and is useful for treating giantosis and the like.

Example 4 Fat Accumulation Inhibitor (1) Synthesis of Peptide A peptide having the amino acid sequence shown in SEQ ID NO: 6 was synthesized using a commercially available peptide synthesizer.

(2) Inhibition of fat accumulation in fat cells RPMI 16 containing 10% fetal bovine serum
The cells were cultured in a 40 medium (source: Dainippon Pharmaceutical) and grown in a 5% carbon dioxide gas humidified 37 ° C incubator. 1 × 10 ⁴ cells / well were seeded on a 96-well culture plate, and when the cells became confluent, the medium was replaced with a serum-free F12 medium and cultured for 8 hours. Thereafter, the peptide of the present invention prepared in (1) was dissolved in a serum-free RPMI1640 medium, and the peptide was added to a well while changing the dose of adipocytes, and the culture was further continued for 24 hours. After the culture, fat accumulation of the cells by the present peptide was determined by the presence or absence of fat granules, and the fat accumulation inhibition in the untreated group was determined. The calculation of the fat accumulation inhibition rate was specifically performed as follows. The fat accumulation rate was determined based on the presence or absence of fat granules, and determined from the number of fat accumulated cells by microscopic observation. The fat accumulation inhibition rate was as follows when the control group without the substance added was taken as 100% and the fat accumulation inhibition rate of the group to which the dose was changed was calculated. Table 3 shows the results.

[0056]

[Table 3] Table 3

As is evident from Table 3, it was confirmed that the above-mentioned peptide of the present invention acts on fat cells as an inhibitor of fat accumulation. Therefore, the present peptide is considered to be linked to the inhibition of fat accumulation, and is useful for obesity and the like.

Example 5 Blood calcium concentration increasing agent (1) Synthesis of peptide Peptides having the amino acid sequences shown in SEQ ID NOs: 7 and 8 were synthesized using a commercially available peptide synthesizer.

(2) Effect on blood Ca concentration in rats The effect on blood Ca concentration was determined by using the peptide synthesized in (1) and calcitonin, which lowers blood Ca concentration, in rats (Wistar species) using physiological saline. The solution dissolved in was injected subcutaneously, and 10 minutes later, the Ca concentration in the blood was measured to evaluate.
Calcitonin was administered at 100 ng / kg, and the peptide of the present invention was administered at 10 μg / kg. The blood Ca concentration was evaluated by measuring the Ca concentration in serum collected from rats. Comparison of the blood Ca concentration between the control group to which the substance was not administered and the administration group was as follows. The results are shown in Table 4 below.

[0060]

[Table 4] Table 4

As is clear from Table 4, the above peptide of the present invention was confirmed to have an effect of increasing blood Ca concentration in rats. Therefore, the present peptide is useful as a therapeutic agent for lowering blood Ca and the like.

Example 6 Gastric Acid Secretion Inhibitor (1) Synthesis of Peptide A peptide having the amino acid sequence shown in SEQ ID NO: 9 was synthesized using a commercially available peptide synthesizer.

(2) Gastric acid secretion inhibitory effect in rats The gastric acid secretion inhibitory effect was determined using rats (Wistar species).
A solution prepared by dissolving the peptide synthesized in (1) and gastrin, which promotes gastric acid secretion, in physiological saline was injected subcutaneously, and the gastric acid secretion was measured 10 minutes later to evaluate. Gastrin is 4
The peptide of the present invention was administered at a concentration of 10 μg / kg so that the concentration became μg / kg. The gastric acid secretion was evaluated by fixing the rat in a fixator, inserting a probe into the stomach through the mouth, collecting gastric juice, and measuring the pH. Suppression of gastric acid secretion was as follows when comparing gastric acid secretion between the control group not receiving the substance and the control group. The results are shown in Table 5 below.

[0064]

[Table 5] Table 5

As is clear from Table 5, it was confirmed that the above-mentioned peptide of the present invention acts on rats to inhibit gastric acid secretion. Therefore, the present peptide is useful as a therapeutic and prophylactic agent for gastric ulcer and duodenal ulcer that suppress gastric acid secretion.

Example 7 Prostaglandin E2 Production Promoter (1) Synthesis of Peptide A peptide having the amino acid sequence shown in SEQ ID NO: 10 or 11 was synthesized using a commercially available peptide synthesizer.

(2) Promotion of Prostaglandin E2 Production by Prostaglandin E2 Producing Cell Prostaglandin E2 producing lung cell SV40 transformant WI-26 VA-4 cells (obtained from ATCC) The cells were cultured in a DME medium (produced by Dainippon Pharmaceutical) containing 5% fetal bovine serum and grown in a 5% CO2 humidified 37 ° C incubator. 1 × 10 ⁴ cells / well were seeded on a 96-well culture plate by trypsin treatment, and when confluence was reached, the medium was replaced with a serum-free DME medium and cultured for 8 hours. Thereafter, the peptide of the present invention produced in (1) was dissolved in a serum-free DME medium, and the peptide was added to WI-26 VA-4 cells while changing the dose, and the culture was continued for another 12 hours. After the culture, the effect of the present peptide on promoting the production of prostaglandin E2 by cells was measured by a prostaglandin E2 immunoassay to determine the effect of promoting the production on the non-treated group.
In addition, the immunoassay of prostaglandin E2 and the calculation of the prostaglandin E2 production promotion rate were specifically performed as follows. Prostaglandin E2 immunoassay was performed by EIA. The prostaglandin E2 production promotion rate was as follows when the control group to which this substance was not added was set to 100% and the prostaglandin E2 production promotion rate of the group to which the dose was changed was calculated. The results are shown in Table 6 below.

[0068]

[Table 6] Table 6

As is evident from Table 6, it was confirmed that the above-mentioned peptide of the present invention acts on prostaglandin E2 producing cells in lung cell-derived prostaglandin E2 producing cells. Therefore, the present peptide is considered to be associated with a decrease in blood pressure, and is useful for treating hypertension and the like.

Example 8 Osteoblast Growth Promoter (1) Synthesis of Peptide Peptides having the amino acid sequences shown in SEQ ID NOs: 12 to 15 were synthesized using a commercially available peptide synthesizer.

(2) Osteoblast proliferation promoting action Rat-derived ROS cells (obtained from ATCC), which are osteoblasts, were cultured in F10 medium (obtained from Dainippon Pharmaceutical) containing 10% fetal calf serum. The cells were grown in a 5% carbon dioxide gas humidified 37 ° C thermostat. 1 × 10 ⁵ cells / well (well) were seeded on a 24-well culture plate by trypsin treatment. When the cells became confluent, the medium was replaced with 1% fetal bovine serum F10 medium and cultured for 24 hours. Thereafter, the peptide of the present invention prepared in (1) was dissolved in 1% fetal bovine serum F10 medium, added to the wells while changing the dose, and the culture was further continued for 24 hours. After culturing, the growth promotion effect of
It was measured by the T assay to determine the growth promoting effect on the untreated group. In addition, the MTT assay and the calculation of the growth promotion rate were specifically performed as follows. Following the procedure of the MTT-Cell-Growth Assay kit commercially available from Funakoshi Co., Ltd., add the substance to the wells while changing the volume of the substance, leave it overnight, and then use the enzyme present in the mitochondria of the viable cells to remove MTT (3-4 , 5Dimetylthiazol-2YL) -2,5Diphenyl Tetrazo
The number of viable cells was counted by a colorimetric method utilizing the phenomenon that lium bromide is cleaved into dark blue formazan. The calorimetric value of the group to which this substance was added was as follows. The results are shown in Table 7 below.
Shown in

[0072]

[Table 7] Table 7

As is evident from Table 7, it was confirmed that the above-mentioned peptides searched by the method of the present invention act on osteoblasts in a growth promoting manner. Therefore, the present peptide is considered to lead to an increase in bone mass, and is useful for treatment and prevention of bone diseases such as osteoporosis.

(3) Presence of a receptor for the present peptide on osteoblasts It has been found that the present peptide has a growth promoting effect on osteoblasts. It is inferred that If the receptor is present, the peptide is considered to be a fundamental substance for life, and then the presence of the receptor in osteoblasts was investigated.

The peptide obtained in (1) is labeled with biotin, and a certain amount of the present peptide is added to ROS cells cultured in the same manner as in (2). Was dissolved in 10% fetal bovine serum F10 medium,
Varying doses were added to see the competitive response. This experimental operation was specifically performed as follows. This peptide is biotinylated according to the procedure of a protein biotinylation labeling kit manufactured by SUMILON, and a fixed amount of biotinylated peptide is added to a certain number of cells seeded in a well to remove unlabeled peptide from 0 to 1.
0 μg / well was added to each and a competition reaction was performed for 6 hours.
The cells are washed with PBS and reacted with a biotinylated peptide bound to a receptor on the cell surface with streptavidin-labeled peroxidase, and a color reaction is observed. If the receptor of the present peptide is present on the cell surface, a competitive reaction occurs with the unlabeled peptide, and the color intensity is reduced. The results are shown in Table 8 below.
Shown in

[0076]

[Table 8] Table 8

As shown in Table 8, since the ratio to the added label varies depending on the amount of non-label added, it is apparent that osteoblasts have a receptor for the present peptide. This suggests that this substance plays a fundamental role. From the above, it is considered that the peptide according to the present invention promotes bone resorption,
It is considered to be a therapeutic and preventive drug for osteoporosis and the like.

Example 9 Growth Hormone Production Promoter (1) Synthesis of Peptide Peptides having the amino acid sequences shown in SEQ ID NOs: 16 to 21 were synthesized using a commercially available peptide synthesizer.

(2) Promotion of Growth Hormone Production of Growth Hormone-Producing Cells Hamster-derived GH3 cells, which are pituitary cells that produce growth hormone (obtained from ATCC), were cultured in F12 medium containing 15% fetal bovine serum (obtained from: (Nippon Pharmaceutical Co., Ltd.) and grown in a 5% CO 2 humidified 37 ° C. incubator. 1x10 ⁴ cells / well were seeded on a 96-well culture plate by trypsin treatment, and when confluent, the medium was reduced to 15%.
The medium was replaced with a serum F12 medium and cultured for 12 hours. Then (1)
Was dissolved in 15% serum F12 medium, added to the wells while changing the dose, and the culture was continued for 3 days. After the culture, the effect of the present peptide on promoting the production of growth hormone by cells was measured by a growth hormone immunoassay, and the effect of promoting the production on the non-treated group was determined. The growth hormone immunoassay and the calculation of the growth hormone production promotion rate were specifically performed as follows.
The cell culture supernatant was added to the wells on which the anti-growth hormone antibody was fixed while changing the dose, and reacted with the anti-growth hormone antibody solution. The detection was carried out by measuring the color of peroxidase labeled on the antibody. The growth hormone concentration was calculated from a growth hormone standard curve. The growth hormone production promotion rate was as follows when the control group without addition of this substance was taken as 100%, and the growth hormone production promotion rate of the group to which the dose was changed was calculated. The results are shown in Table 9 below.

[0080]

[Table 9] Table 9

As is clear from Table 9, it was confirmed that the above-mentioned peptide of the present invention acts on growth hormone-producing cells to promote growth hormone production. Therefore, the present peptide is considered to be linked to promotion of growth, and is useful for treatment of dwarf disease and the like.

[0082]

As described in detail above, according to the present invention,
Demonstrates excellent pharmacological effects and has a completely different mechanism of action from conventional drugs, blood pressure suppressing effect, analgesic effect, growth hormone production inhibitory effect, fat cell fat accumulation inhibiting effect, gastric acid secretion inhibiting effect, blood calcium concentration A novel compound having a stimulatory effect, an inhibitory effect on gastric acid secretion, a prostaglandin E2 production promoting effect, an osteoblast proliferation promoting effect or a growth hormone production promoting effect, and a pharmaceutical use thereof are provided.

[0083]

[Sequence List] SEQUENCE LISTING <110> SAKAMOTO BIO FARM CO. LTD. <120> Novel Peptides and Their Uses as Pharmaceuticals <130> 00636 <160> 21

<210> 1 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Polypeptide having activity to reduce blood pressure <400> 1 Gly Leu His Phe Gly Leu Val Asn Ile Ser Gly Asn Asn Glu Ser Thr Leu 1 5 10 15

<210> 2 <211> 27 <212> PRT <213> Artificial Sequence <220> <223> Polypeptide having activity to reduce blood pressure <400> 2 Met Phe Ser Pro Trp Lys Ile Ser Met Phe Leu Ser Val Arg Glu Asp 1 5 10 15 Ser Val Arg Thr Thr Ala Ser Phe Ser Ala Asp 20 25

<210> 3 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Polypeptide having analgesic activity <400> 3 Glu Glu Asn Ile Gln Cys Gly Glu Asn Phe Met Asp 1 5 10

<210> 4 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Polypeptide having analgesic activity <400> 4 Gln Arg Gly Thr Gln Lys Ser Ile Ile Ile His Thr Ser Glu Asp Gly Lys Val 1 5 10 15

<210> 5 <211> 24 <212> PRT <213> Artificial Sequence <220> <223> Polypeptide having activity to inhibit production of growth hormo ne <400> 5 Gly Ser Glu Ala Thr Ala Ala Ile Leu Ser Arg Ala Pro Trp Ser Leu 1 5 10 15 Gln Ser Val Asn Pro Gly Leu Lys 20

<210> 6 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Polypeptide having activity to inhibit accumulation of fat in fat cells <400> 6 Glu Pro Glu Leu Ile Asp Ser Thr Lys Leu 1 5 10

<210> 7 <211> 6 <212> PRT <213> Artificial Sequence <220> <223> Polypeptide having activity to increase calcium level in blood <400> 7 Ser His Val Tyr His Glu 15

<210> 8 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Polypeptide having activity to increase calcium level in blood <400> 8 Lys Glu Ala Pro Thr Gly Ser Arg Tyr Arg Gly Arg Pro 1 5 10

<210> 9 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Polypeptide having activity to inhibit secretion of gastric acid <400> 9 Gly Gly Asn Gly Thr Ser Ser Ser His Asn Trp Gly Asn 1 5 10

<210> 10 <211> 15 <212> PRT <213> Artificial Sequence <220> <223> Polypeptide having activity to increase production of prostagland in E2 by prostaglandin E2-producing cells <400> 10 Arg Arg Pro Pro Pro Ala Ser Gly Pro Asp Ser Arg Arg Arg Trp 1 5 10 15

<210> 11 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Polypeptide having activity to increase production of prostagland in E2 by prostaglandin E2-producing cells <400> 11 Ala Ser Ala Ser Thr Phe Phe Gly Gly Ser Arg 1 5 10

<210> 12 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Polypeptide having activity to stimulate proliferation of osteobl asts <400> 12 Thr Thr Ile Phe Pro Leu Asn Trp Lys Tyr Arg Lys Ala Leu Ser Leu 1 5 10 15

<210> 13 <211> 36 <212> PRT <213> Artificial Sequence <220> <223> Polypeptide having activity to stimulate proliferation of osteobl asts <400> 13 Met His Ile Phe His His Asn Thr Tyr Met Trp Thr Met Gln Trp Glu 1 5 10 15 Leu Ser Pro Pro Leu Pro Ser Ala His Glu Gly Lys Met Asp Pro His 20 25 30 Asp Ser Glu Val 35

<210> 14 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Polypeptide having activity to stimulate proliferation of osteobl asts <400> 14 Gly Phe Phe Val Ala Thr Ile Tyr Cys Phe Cys Asn Asn Glu 1 5 10

<210> 15 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Polypeptide having activity to stimulate proliferation of osteobl asts <400> 15 Tyr Phe Asn Leu Leu Ala Pro Phe Asn Ala Leu Leu Tyr Pro Thr Arg 1 5 10 15

<210> 16 <211> 9 <212> PRT <213> Artificial Sequence <220> <223> Polypeptide having activity to increase production of growth horm one by growth hormone-producing cells <400> 16 Asp Gly Met Glu Glu Pro Gly Arg Asn 1 5

<210> 17 <211> 9 <212> PRT <213> Artificial Sequence <220> <223> Polypeptide having activity to increase production of growth horm one by growth hormone-producing cells <400> 17 Ser Ser Ala Pro Ala Glu Ala Glu Glu 1 5

<210> 18 <211> 5 <212> PRT <213> Artificial Sequence <220> <223> Polypeptide having activity to increase production of growth horm one by growth hormone-producing cells <400> 18 Gly Gly Gln Ala Val 1 5

<210> 19 <211> 3 <212> PRT <213> Artificial Sequence <220> <223> Polypeptide having activity to increase production of growth horm one by growth hormone-producing cells <400> 19 Ala Pro Ser 1

<210> 20 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Polypeptide having activity to increase production of growth horm one by growth hormone-producing cells <400> 20 Ser Cys Gln Trp Val Gln Ala Pro 1 5

<210> 21 <211> 31 <212> PRT <213> Artificial Sequence <220> <223> Polypeptide having activity to increase production of growth horm one by growth hormone-producing cells <400> 21 Arg Pro Ser Arg Arg Val Arg Ser Gln Glu Pro Thr Val Gly Pro Pro 1 5 10 15 Glu Lys Thr Glu Glu Glu Asp Glu Glu Glu Glu Asp Gly Glu Glu 20 25 30

[Brief description of the drawings]

FIG. 1 is a graph showing the blood pressure suppressing effect of the peptide of the present invention prepared in Example 1.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI theme coat ゛ (Reference) A61P 5/06 A61P 5/08 5/08 9/08 9/08 9/12 9/12 19/10 19 / 10 29/00 29/00 43/00 112 43/00 112 C07K 5/083 C07K 5/083 7/06 7/06 14/00 14/00 C12P 21/02 H // C12P 21/02 31/00 31/00 (C12P 21/02 H (C12P 21/02 C12R 1:91) C12R 1:91) (C12P 31/00 (C12P 31/00 C12R 1:91) C12R 1:91) A61K 37/02 F-term (Reference) 4B064 AG13 AH06 CA10 CA19 CD20 DA01 4C084 AA02 AA07 AA21 BA01 BA15 BA16 BA17 BA18 BA19 CA59 DB22 DB60 DB79 NA14 ZA082 ZA392 ZA422 ZA682 ZA972 ZC032 ZC122 ZC332 4H045 AA10 BA15 EA18 BA18 EA23 EA30 FA34

Claims (36)

[Claims] 1. A peptide having an amino acid sequence represented by SEQ ID NO: 1 or 2 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 suppressing effect. 2. The peptide according to claim 1, wherein a peptide having an amino acid sequence represented by SEQ ID NO: 1 or 2 is used as an active ingredient. 3. A pharmaceutical comprising the peptide according to claim 1 as an active ingredient. 4. The medicament according to claim 3, which is a blood pressure suppressant. 5. A peptide having an amino acid sequence represented by SEQ ID NO: 3 or 4 in the sequence listing or 1
Or a peptide having an analgesic effect, wherein the peptide has an amino acid sequence in which a plurality of amino acids have been substituted or deleted, or one or more amino acids have been inserted or added to the amino acid sequence. 6. The peptide according to claim 5, wherein a peptide having an amino acid sequence represented by SEQ ID NO: 3 or 4 is used as an active ingredient. 7. A medicament comprising the peptide according to claim 5 or 6 as an active ingredient. 8. The medicament according to claim 7, which is an analgesic. 9. A peptide having the amino acid sequence represented by SEQ ID NO: 5 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 inserted into the amino acid sequence. A peptide having an added or added amino acid sequence and having a growth hormone production inhibitory effect. 10. The peptide according to claim 9, which comprises a peptide having the amino acid sequence represented by SEQ ID NO: 5 as an active ingredient. 11. A pharmaceutical comprising the peptide according to claim 9 or 10 as an active ingredient. 12. The medicament according to claim 11, which is a growth hormone production inhibitor. 13. A peptide having the amino acid sequence represented by SEQ ID NO: 6 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 inserted into the amino acid sequence. A peptide having an added or added amino acid sequence and having an effect of inhibiting fat accumulation in adipocytes. 14. The peptide according to claim 13, which comprises a peptide having the amino acid sequence represented by SEQ ID NO: 6 as an active ingredient. 15. A medicament comprising the peptide according to claim 13 or 14 as an active ingredient. 16. The medicament according to claim 15, which is a fat accumulation inhibitor. 17. A peptide having an amino acid sequence represented by SEQ ID NO: 7 or 8 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 Is a peptide having an amino acid sequence inserted or added, which has an effect of increasing blood calcium concentration. 18. The peptide according to claim 17, which comprises a peptide having an amino acid sequence represented by SEQ ID NO: 7 or 8 as an active ingredient. 19. A medicament comprising the peptide according to claim 18 or 19 as an active ingredient. 20. The medicament according to claim 19, which is a blood calcium concentration increasing agent. 21. A peptide having the amino acid sequence represented by SEQ ID NO: 9 in the sequence listing, or substitution or deletion of one or more amino acids in the amino acid sequence, or insertion of one or more amino acids into the amino acid sequence A peptide having an added or added amino acid sequence and having a gastric acid secretion inhibitory effect. 22. The peptide according to claim 21, comprising a peptide having the amino acid sequence represented by SEQ ID NO: 9 as an active ingredient. 23. A pharmaceutical comprising the peptide according to claim 21 as an active ingredient. 24. The medicament according to claim 23, which is a gastric acid secretion inhibitor. 25. A peptide having the amino acid sequence represented by SEQ ID NO: 10 or 11 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 Is a peptide having an amino acid sequence in which is inserted or added, wherein the peptide has a prostaglandin E2 production promoting effect. 26. A peptide having an amino acid sequence represented by SEQ ID NO: 10 or 11 as an active ingredient.
The peptide according to claim 1. 27. A medicament comprising the peptide according to claim 25 or 26 as an active ingredient. 28. The medicament according to claim 27, which is a prostaglandin E2 production promoter. 29. A peptide having an amino acid sequence represented by SEQ ID NO: 12, 13, 14 or 15 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. Alternatively, a peptide having an amino acid sequence in which a plurality of amino acids have been inserted or added, and having an osteoblast proliferation promoting effect. 30. The peptide according to claim 29, wherein a peptide having the amino acid sequence represented by SEQ ID NO: 12, 13, 14, or 15 is used as an active ingredient. 31. A medicament comprising the peptide according to claim 29 or 30 as an active ingredient. 32. The osteoblast proliferation promoter.
The medicament according to claim. 33. SEQ ID NO: 16, 17, 18, or
A peptide having the amino acid sequence represented by 19, 20, or 21, or an amino acid in which one or more amino acids in the amino acid sequence are substituted or deleted, or one or more amino acids are inserted or added to the amino acid sequence A peptide having a sequence and having a growth hormone production promoting effect. 34. SEQ ID NO: 16, 17, 18, 19, 2
34. The peptide according to claim 33, comprising a peptide having an amino acid sequence represented by 0 or 21 as an active ingredient. A pharmaceutical comprising the peptide according to claim 33 or 34 as an active ingredient. 36. The medicament according to claim 35, which is a growth hormone production promoter.