JPS62223120A - Method for controlling biofunction - Google Patents

Abstract

PURPOSE:To enable antagonistic control of the function of a first prostaglandin (PG), by using corresponding second and third PGs of other types to the first PG to be controlled. CONSTITUTION:In the case of suppressing or promoting the action of the first PG in a series, the second and the third PGs of the other two series corresponding to the first PG and/or precursor substances of the second or third PG are administered to control the function of the first PG. The precursor is e.g. gamma- linolenic acid or di-homo-gamma-linolenic acid for PG1 and eicosapentaenoic acid or docosahexaenoic acid for PG3. One of the above precursors forms the objective controlling substance in living body. For example, fever and pain can be suppressed by administering PGE1 and PGE3 to PGE2 having strong participation in inflammation, fever and pain.

Description

[Detailed Description of the Invention] Industrial Application Field This invention focuses on the three types of PGs that exist in living organisms.
In particular, for a first PG intended for coordination, two corresponding second PGs. By using @30PG and/or their precursors, the function of the 10th PG can be antagonistically inhibited by y4
11M.

PRIOR ART PGs are local hormones produced in the organs and glands of the living body, and play a role in regulating the functions of the living body, and have the following particularly notable effects.

Platelet # collection PGH, TXA Platelet aggregation inhibition PGD, PCI Vasoconstriction TXA (Lonphoxane) Vasodilation PCI Bronchial constriction PGF, PGH Bronchodilation PGE Blood pressure decrease PGE Uterine contraction PGE Smooth muscle contraction TXC, LTC (leukotriene C) TD Immune function Decreasing PGE when adjusting for excesses or deficiencies in many of these functions,
Various drugs have been used in the past. For example, Phos7-oliverase A, which liberates arachidonic acid (AA) from phospholipids.
Aspirin and indomethacin inhibit the activity of cyclooxygenase that converts AA to PGz, and imidazole inhibits the enzyme activity of converting PGHz to TXAt.

There are three types of PGs depending on the starting material: type 1 (PGl), type 2! I (PC2), 3a (PGg)
have 1 and 2.3 double bonds in their side chains, respectively.

Among these three 凰 or series, type 2 is generally superior in both quality and quantity, so progress has been made centered on type 2 from an early stage. There is a clear relationship between the production route, physiological effects, and the series. On the other hand, regarding the other two series PG1゜PGs, research based on the four assumptions from PGz has just begun, let alone PGl.
*The reality is that little is known about the interaction between the three series of PQ 2 + P G s.

This invention aims to create a healthy body by preventing or treating various disorders involving PGs.

The problem that the invention aims to solve Until now, various drugs have been used to correct the excessive or insufficient regulation of biological functions by PG, but all of them have drawbacks such as side effects and inadequate efficacy. However, there were very few things that could be used safely and continuously. Therefore, it has become extremely difficult to prevent or treat various disorders involving PGs.

Means for Solving Intervertical Vertices The inventor focused on the mutual relationship between the three series, type 1, type 2, and type 3, and completed the present invention as a result of repeated research.

In vivo, when attempting to suppress or promote the action of the first PG of one series, the second PG of the other two series corresponding to the first PG should be suppressed or promoted. We have now discovered a way to modulate the functional function of a first PC by administering a third PC and/or its precursor. Once the type of PG that requires adjustment is determined, the other two types of PG are determined by themselves. In addition, when precursors are used, one or two precursors for each series become precursors for all 20 items of each series, and thus show a comprehensive antagonistic effect between each series.

If the PC for the purpose of adjustment is assumed to be PGz, the diagram will be as follows.

PC2 in vivo pa! JR has 3 PGt * PC2t PGs.
There are 18 strains, each with different skeletal structures, each with different physiological activities. PC family in a narrow sense.

Trompixane (TX) table, leukotriene (LT)
) There is a basic structure of 544 types. (Table-1) Table-
1 The corresponding PGs in this invention include, for example, PGA1 and PGA= for PGAz, and pGKt for PGEz.
and PGKs, T X B 1 and TXBs for TXB2, I, TDl and L for LTD4
TD, , t or PG I s as PGll and PGIt (Table 1).

! The ratio of the other two types of PG or precursors to the PG for conditioning purposes may be equal or arbitrary depending on the situation.

The PGs and precursors used are chemical, synthetic, biosynthetic, natural extraction methods, raw materials, six products, free form, bound form, derivatives, chemical structure, purity, etc., and there are no side effects. It can be used as long as it is safe and legal.

In the case of precursors, P C,1 is γ(gamma)-lylunic acid (GLA) or dihomogammalylunic acid (DGL
A), PGg is limited to arachidonic acid (5 people), and PGs is limited to either eicosapentaene fi (KPA) or tahadocosahexaenoic acid (DHA), and one of these is the target substance for regulation in vivo.

Until microbial production becomes possible, sources of GLA include evening primrose oil (8% in glyceride fatty acids), El
:PA is concentrated fish oil (EPA in glyceride fatty acids)
25%, DHA 13%), marine chlorella oil (EPA
About 35% of fatty acids).

The method of administration includes body ffilFw per day, PG
In the case of precursors, several micrograms to several hundred micrograms of active ingredients are administered, and in the case of precursors, several milligrams to several hundred milligrams of active ingredients are administered alone or as a composition. The state is an emulsified dispersion.

Injection (subcutaneous) as saline solution, oil solution, etc.

A method suitable for the purpose is selected from among methods such as intravenous, oral, rectal, intraluminal, intraperitoneal, etc., but is not limited to these methods.

The shape of the product we supply is soft capsule.

It can be made into ampoules, bottles, tablets, powders, pellets, drinks, candies, jellies, and many other pharmaceutical, food, and a-material forms.

Effect This invention has the same basic structure as the first PG to be adjusted, but there are differences (strength or weakness of the same effect) caused by only one or two differences in double bonds.

The second type shows contradictory effects, etc.). By using the third PG and/or their precursor vJ in combination and coexisting with the first PC or its precursor in vivo, the first
This is a method for suppressing or promoting the production or action of PG.

PGH2 has a platelet aggregation effect, whereas P
and P GHs both inhibit aggregation. Therefore A.A.
By administering PGH1 and PGHs to a living body simultaneously or as a composition, a strong and effective aggregation-inhibiting effect can be exerted on the action of PGH1 and PGHs in the living body. Also inflammation 2 fever.

By administering %PGF:1 and PGFI: to PGE2, which is strongly involved in pain, it is possible to suppress fever and pain.

The mechanism of action of this invention is explained as follows.

(Figure 1) When the PG for adjustment purpose is set as PGEz, the corresponding P
G becomes pGgt and P G E s. The precursors are DGLA or DGLA and EPAK.

(1) In normal living organisms, PGE2 is produced by cyclooxygenase.

(2) for the progression of (1) (3) for the product PGEzK, PGEt and PGEM;
antagonize and suppress the effect.

Examples Example I A composition of 1 volume of ethanol solution was prepared by dissolving 25 volumes each of PGHI and PGHs. For comparison, PGHz
50"F was dissolved to make an ethanol solution.

Through a catheter inserted into the artery of a Japanese rabbit.

After adding 0.1 times the blood volume of 3.8 sodium citrate, the blood was collected, centrifuged (1100 rpm), and platelet rich solution (PRP) with a platelet count of 5 x 10'/d was collected.
It was AM.

P RP 200μ in the cuvette of the abrebometer
t, PC ethanol solution or 1 μt of ethanol as a control, and an aggregation-inducing substance at a final concentration of 7.5 μM [ADP (adenosine di-7 osphaerate)].

Collagen: 20 μm/d, Human A: 50 μm/d) were added to induce platelet collection, and changes in absorbance were measured over time. As a result of calculating the maximum aggregation inhibition ability (%) from the ratio of the control and test solution at the maximum absorbance, it was found that P for all ADP, collagen, and AA
The combination of GHt and PGHs is PGf(x, PGH
g showed a remarkable aggregation inhibiting effect compared to each alone.

(Margin below) Sample concentration = 250μ2/go In addition, in the case of PGHg, it showed Illll retention effect.

Example 2 The above composition was made into 300Mq soft capsules, and 6 capsules per day were administered to three adult males with hypercholesterolemia.
Administered for 2 months. After 2 months, serum cholesterol, H
DL cholesterol/'1llJ constant, compared with before taking. Evening primrose oil and concentrated fish oil alone were administered to 1.
It was measured.

The measured values were above the average values for each of the three subjects, indicating that (GLA+EPA) was able to significantly improve hypercholesterolemia in a competitive manner against the PG regulatory function centered on AA derived from food in the living body.

Example 3 White domestic rabbit (male, weight 2.5 Kg to 3 Kg) 6
The rats received intravenous injections of 200 micrograms of PGE2 per day every day for 2 weeks, and 3 of them received PGEI and PGE in the same manner for the latter week.
Additional doses of 100 micrograms each were administered. Two weeks later,
The amount of PGEZ in blood, the number of lymphocytes, and the ratio of TMU count to BM cell number (microplate method) were measured, including controls. (Average value for each 3 animals) When PGE was administered alone, as blood PG Ex increased, both the number of lymphocytes and the ratio of Td cells to Bjffl cells decreased, leading to a decrease in immunity. However, when PGE and PGEs were co-administered, PGE
The increase in GE2, the decrease in lymphocytes, and the decrease in the proportion of T cells were all suppressed, and immunity did not decrease at all.

Example 4 When patients suffering from inflammatory diseases such as pneumonia, tonsillitis, and otitis media were given 10 capsules per day of the capsules containing GLA and EPA prepared in Example 2, inflammation was observed 24 to 36 hours later. .

The pain and fever subsided, and the patient returned to normal after 48 to 60 hours. This is due to antagonism, AA to PGx (TX,
This is presumed to be due to the suppression of conversion to LT).

Effects of the Invention This invention solves the problem of excessive or insufficient action of one important function involving PCs, which has strong side effects and lacks suitability of action and effect.
Being able to adjust it in a natural and safe way without using conventional drugs will greatly contribute to a person's health and well-being.

It also has the potential to provide a means of preventive treatment for acquired immunodeficiency syndrome, which has become a major threat in recent years.

[Brief explanation of drawings]

FIG. 1 is a drawing explaining the invention in detail.

Claims (3)

[Claims] (1) Three types of prostaglandins (P
G) A method for regulating a biological function using two other corresponding second and third PGs and/or precursors thereof for the first PG to be adjusted. (2) The first PG for the purpose of adjustment is a type 2 PG (PG_
2), the corresponding second and third PGs are each type 1 PG (
PG_1) and type 3 PG (PG_3). (3) The first PG_2 for the purpose of adjustment is PGE_2,
The corresponding second and third PG_1 and PG_3 are P
The adjustment method according to claims 1 and 2, which are GE_1 and PGE_3.