JPS60202815A - Reinforcing agent for blood vessel - Google Patents

Abstract

PURPOSE:A reinforcing agent for blood vessel having protecting action on blood vessel disorder in hypertensive diseases, comprising a specific fatty acid or its salt as an active ingredient. CONSTITUTION:The titled agent comprising a compound shown by the formula I [group shown by the formula II is single bond, or double bond (cis form); m is 0, or 6; n is 7, or 8], or its salt, such as undecylenic acid, palmitic acid, etc. as an active ingredient. The reinforcing agent for blood vessel has recovering action on fragility and extraordinary permeability of blood vessel, reinforcing action on blood vessel, preventing action on aging of blood vessel, showing effect especially on hypertensive blood vessel disorder, particularly on cerebrovascular disorder, it is effective for preventing and remedying cerebral apoplexy, and 1-200mg/kg day, preferably 40-150mg/kg day calculated as free acid of the active ingredient compound is administered.

Description

[Detailed description of the invention] Technical field TECHNICAL FIELD The present invention relates to vascular reinforcing agents.

BACKGROUND OF THE INVENTION Stroke, a hypertensive disease, is one of the major causes of death in Japanese people. Once a stroke occurs, it has a high mortality rate - even if it does not lead to death, it is difficult to completely cure it and is the most common incurable disease, leaving people in a so-called "bedridden" state.To overcome this disease, appropriate preventive measures must be taken before the onset of the disease. There is no proper way other than to do so.

Hypertension develops due to the interaction of genetic and environmental factors, and 8HR type rats) (5HR8P: 100% of rats spontaneously develop severe hypertension, and more than 90% of them develop apoplexy and die; JPNclrcul, J , 4
1259 (1977)) to search for genetic factors related to hypertension and stroke, it was found that genetic factors related to hypertension and stroke exist separately, and that they are thought to be closely related to each other. ing. In other words, if you have both high blood pressure and stroke genetic factors, you will naturally be more likely to develop a stroke, but even if the genetic factors for hypertension do not have a strong contribution (even if you do not have severe hypertension), the contribution of genetic factors related to stroke will increase. In severe cases, even mild hypertension can cause a stroke.

Currently, antihypertensive drugs are the mainstream drugs for treating hypertensive diseases. However, considering the above-mentioned experimental results using 5HR8P, in order to overcome hypertensive diseases, antihypertensive drugs alone are not sufficient, and drugs that act from completely different aspects are required. One possible example is a vascular reinforcing agent that reduces cerebrovascular disorders even in patients with hypertension. This is because when hypertension occurs, a significant load is placed on the vascular system (mainly the arterial system), and membrane disorders such as increased permeability of blood vessel wall cells occur, resulting in blood vessel necrosis and blood vessel failure. This is because blood vessels can rupture and cause bleeding (cerebral hemorrhage), or blood clots may form in necrotic areas of blood vessels (cerebral infarction).

Currently known vascular reinforcing agents include the vitamin P group of rutin, hesveridin, and eriocidrin. However, these drugs are poorly absorbed from the intestinal tract and are rapidly excreted after injection, so their effectiveness as vascular reinforcing agents is questionable, and they also have side effects such as hypersensitivity and gastrointestinal disorders. It's not something to be satisfied with.

Purpose and Structure of the Invention Under the present circumstances, the present inventors have conducted intensive research to develop a novel vascular reinforcing agent. It has been found that it has a protective action and can be effectively used as a vascular reinforcing agent. The present invention has been completed based on such knowledge.-0 That is, the present invention is based on the general formula [wherein, C=, C represents a heavy or double bond (V-substance)]. m is 0 or 6, and n is 7 or 8. ] A blood vessel reinforcing agent characterized by containing a fatty acid represented by the following and its salt as an active ingredient.

In the present invention, the fatty acid of general formula (I), which is an active ingredient, is contained in a considerable amount in various vegetable and animal fats and oils, typically milk fat, fish oil, whale oil, apple, etc. It can be isolated by conventional methods such as molecular distillation, countercurrent distribution, chromatography, etc., and some are commercially available as standards. However, for practical purposes, this does not necessarily have to be a particularly isolated and purified pure product (it may also be a crude product containing a small amount of other fatty acids, etc.). It may be organically synthesized.

In the present invention, pharmacologically acceptable salts of the above compounds can also be used as active ingredients in the same manner as the above compounds. The pharmacologically acceptable salts typically include alkali metal salts, alkaline earth metal salts such as sodium salts, potassium salts, calcium salts, and aluminum salts, other metal salts, ammonium salts, morpholine, piperazine, and trimethylalcohol salts. Examples include amine salts such as carbon and di-technical amines.

Although the active ingredient compound of the vascular reinforcing agent of the present invention can be administered alone, it is usually administered in the form of a pharmaceutical composition together with a pharmaceutical carrier. Examples of carriers include fillers, extenders, binders, wetting agents, and
Examples include diluents or excipients such as disintegrants, surfactants, and lubricants.

As the dosage unit form of the pharmaceutical composition, various forms can be selected depending on the purpose, and representative examples include single tablet, emulsion, dosing, liquid, suspension, emulsion, granule, capsule, suppository, Examples include injections (solutions, suspensions, etc.). When molding into tablet form, carriers such as lactose, sucrose, IJ chloride, glucose solution, urea, starch,
Excipients such as calcium carbonate, kaolin, crystalline cellulose, silicic acid, water, ethanol, propatool, simple syrup, glucose, glycol, glycerin, starch liquid,
Gelatin solution, carboxymethylcellulose, shellac, methylcellulose, potassium phosphate, binders such as polyvinylpyrrolidone, starch, sodium alginate,
Disintegrants such as agar powder, una powder, sodium hydrogen carbonate, calcium carbonate, Twin, sodium lauryl sulfate, stearic acid monoglyceride, lactose, disintegration inhibitors such as sucrose, stearin, cocoa butter, hydrogenated oil, quaternary Absorption enhancers such as ammonium bases and sodium lauryl sulfate, humectants such as glycerin and starch, adsorbents such as starch, lactose, kaolin, bentonite, and colloidal silicic acid, purified talc, stearate, boric acid powder, and macrogol. , solid polyethylene glycol, and other lubricants can be used. When forming into an emulsion, carriers include excipients such as glucose, lactose, starch, cacao butter, hydrogenated vegetable oil, kaolin, and talc; binders such as gum arabic powder, tragacanth powder, gelatin, and ethanol;
Disintegrants such as laminaria and agar can be used. Furthermore, the tablets can be made into conventionally coated tablets, such as sugar-coated tablets, gelatin-encapsulated tablets, enteric-coated tablets, film-coated tablets, double tablets, or multilayer tablets, if necessary. When forming into a suppository, for example, polyethylene glycol, cacao butter, higher alcohols, esters of higher alcohols, gelatin, semi-synthetic glycerides, etc. can be used as carriers. When prepared as injectables, solutions and suspensions are preferably sterile and isotonic with blood;
When forming these solutions, emulsions, and suspensions, diluents such as water, ethyl alcohol, propylene glycol, ethoxylated instearyl alcohol, polyoxylated instearyl alcohol, polyoxyethylene sorbitol, and nrubitan ester are used. can be used. In this case, sufficient amounts of common salt, glucose or glycerin may be included in the preparation to provide an isotonic solution. Further, when forming the composition into a paste, cream or gel form, for example, white vaseline, paraffin, glycerin, cellulose derivatives, polyethylene glycol, silicone, bentonite, etc. can be used as a diluent.

Furthermore, the vascular reinforcing agent of the present invention contains antioxidants such as butylated hydroxytoluene, propyl gallate,
Quinone, a-)copherol, etc., as well as usual solubilizing agents, M-adhesive agents, laxatives, preservatives, coloring agents, fragrances, flavoring agents, sweeteners, etc., and other pharmaceuticals such as platelet aggregation inhibitors, etc. It can be included.

The amount of the active ingredient compound to be contained in the pharmaceutical composition is not particularly limited and can be appropriately selected within a wide range, but it is usually 0.01% by weight or more in the total composition, and in the case of tablets, for example, the weight in terms of free acid. On a standard basis, each tablet contains about 0.01 to II of the exfoliating ingredient compound.

Furthermore, there are no particular restrictions on the use of the vascular reinforcing agent of the present invention, and it can be administered in a manner appropriate for each implant type.

Tsunatsubo 1 - J'ronwari 711 Ankyaku 1 縣斎骪 - 連連 - 關閎鋪 - 連連 - 韜 Candy and capsules are administered orally, and injections are administered alone or with normal drugs such as glucose and amino acids. It is administered intravenously by mixing with a replacement fluid, and if necessary, it is administered alone intramuscularly, subcutaneously, subcutaneously, or intraperitoneally, in the case of a suppository, it is administered rectally, and in the case of women, it is administered intravaginally. obtain. The dosage of the preparation is appropriately selected depending on the administration method and the patient's symptoms, and generally the amount of the active ingredient compound is about 1 to 200 eQli/Kl·day, preferably 40 to 150 ml/day in terms of free acid. Kl/-day, which is usually administered in 8 to 4 divided doses per day.

Furthermore, the above-mentioned active ingredient compound of the present invention can be ingested by the patient in the required amount in the form of glyceride as margarine, putter, cooking oil, fat, etc.
Therefore, the present invention also provides a vascular reinforcing agent in the form of food containing such unique fats and oils.

Thus, according to the present invention, a blood vessel reinforcing agent unprecedented in the prior art is provided.

It has been confirmed by various pharmacological tests that the fatty acids of the general formula 4x) and their salts, which are the active ingredients in the present invention, have the above-mentioned effects. It is also confirmed by measuring changes in morphological properties. The test is described, for example, in the literature [Jap, Hea
rt J, 16.296 (1975)) are fed with feed supplemented with W/W%. At an appropriate time point until the snack control (active ingredient-free group) died from a stroke, the rat was decapitated, the removed aorta was kept in cold physiological saline for 24 hours, and then placed in a chuck. A piece of clothing (gX10ms+) having the following is created. After measuring the thickness of the six pieces using a micrometer, it was confirmed that the tensile strength was greater than that of Instron Control, and that the blood vessels were reinforced.

Test example 1 This experiment used a 2 month old male 5HR8F.

In the first experiment, 5HR8F were fed with the two types of feed shown in Table 1 (feed 1.II). 5HR8P was fed with 9 animals on feed I and 8 animals on feed II), and blood pressure and The incidence of stroke was observed.

Table 1 Table 1 (Continued) Table 1 (Continued) Table 1 (Continued) Figure 1 shows the effects of feed on blood pressure. This shows the influence of II, 5uRspo4? It is a graph showing the relationship between (day) and blood pressure. From FIG. 1, it can be seen that in the case of feed ■, the increase in blood pressure tends to be slightly suppressed in the initial stage. Furthermore, the incidence of stroke up to 220 days after birth was 60% for feed I, but 0% for feed ■. Even when observed at final natural death, the incidence of stroke was 194% for feed 1 and feed I[1B
There was a significant difference in %.

The mild pressor suppressing effect of feed (■) is first thought to be due to the difference in protein composition between feeds (■) and (2).

Therefore, we conducted the following experiment. That is, 5H consisting of 8 animals per group.
When feeding R8F with feed I, add 1 methionine to feed L.
5 wt% was added, and the relationship between age (days) and blood pressure was investigated by inertial administration of methionine.

The results are shown in Figure 2. FIG. 2 also shows the results when feed I without methionine was fed to 5HR8F (10 animals per group) as a control. As shown in Figure 2, among the protein-constituting amino acids, the content amino acid (methionine) significantly suppresses the increase in blood pressure and reduces the onset of stroke by approximately 178%.
decreased to However, the amount of methionine added to the feed at this time was 1.6% (W/w), which is much larger than the difference in methionine content between feeds I and ■ (0.18, p/100g feed). From this, it became clear that the stroke-reducing effect of feed ■ cannot be attributed solely to the difference in protein content.

Next, the fat components of Feeds I and II were analyzed, and the results were as shown in Table jI2 below.

Table 82 In the above Table 2, the content is significantly different from that of palmitooleic acid (in the general formula CIl, % 2CHHH'-k indicates a double bond (monoisomer), m xx 6 and 1) am
7, hereinafter referred to as [POAJ], and feed ■ (fat content 6.2%) is a feed compound (fat content 4.6%).
), it contained about 16 times more POA.

Next, in order to clarify whether POA has an effect of suppressing stroke onset, the present inventors prepared a feed similar to feed ①.
(Feed ■) was prepared. This feed had the same amino acid content as Feed I, and the fat content was 4.1%, which was almost the same as Feed I, but the POA content was reduced from 8.8% in Feed H to 0.7%, about 1/6th. This is what I did. Table 8 shows the contents of various components in feed m. Table 4 also shows the analysis results of the fat components in feed m.

Table 8 Table 8 (Continued) Table 8 (Continued) Table 4 This experiment was conducted using 1% water as drinking water for the purpose of shortening the experiment period.
A saline solution was used. In other words, when 8H18P were reared in 1% saline (10 animals per group), blood pressure rose rapidly, the onset of stroke was accelerated, and the incidence of stroke was high.The results obtained were as follows. there were.

The incidence of stroke after 6 weeks of feeding was determined by feeding I, III,
(2) was highest, at 68%, 89%, and 0%, respectively. After 10 weeks of feeding, the incidence of stroke increased, and feed 1. I[[,■ were 79%, 77%, and 61%, respectively. Figure 8 shows these results in terms of the relationship between stroke incidence and survival days.

The peak of stroke onset was earliest for feed I, followed by feed M.
, Feed ■. This indicates that POA suppresses cerebrovascular disorders regardless of its antihypertensive effect.

To further confirm this, milk fat with high POA content (
Feed II was prepared by adding 20% fat content (POA content is approximately 44 times that of Feed Formula) to Feed I, and it was investigated whether this feed is effective against cerebrovascular disorders. . In experiment B, tap water was used as drinking water. Also 5HR8F
For feed 1, 14 animals were used, and for feed 2, 20 animals were used.

The results are shown in Figure 4 (1) and (b), and there was no difference in blood pressure increase between feeds 1 and W. The incidence of stroke caused by diet I was approximately 88% when observing all natural deaths, but it was very low at approximately 6% with diet II, and the survival life was also 826 days compared to the average of 806 days. It was extended.

Test Example 2 5HR8P, 8 months old, was divided into groups shown in Table 6 below and reared with ad libitum access to 1% saline and feed (SP, manufactured by Funabashi Farm ■), and the survival rate was measured over time. . No differences were observed in food intake and water intake in either group.

The results of measuring the survival rate over time for Test I and Test II in Table 5 are shown in FIGS. 6 and 6, respectively. As is clear from FIGS. 6 and 6, POA, which is the active ingredient of the present invention,
undecylenic acid (a compound in which C=C in the general formula (I) is a double bond, m wx Q and n w g) and pallic acid (in the general formula (I), \c =, c'' is - It was confirmed that a compound with double bonds, m6 and n-7 (compound) has an extremely strong stroke prevention effect.

In addition, test I (control and group A) in the above test
blood pressure per rat
The time-course changes in RESUR・) were measured. The results are shown in Table 6 below. The numbers in Table 6 are the main standard errors of the mean, and n is the rat comparison.

Table 6: No difference in blood pressure was observed between Group A and the control, and the results shown in Table 6 revealed that POA did not exert its preventive effect on stroke by lowering blood pressure. .

Test Example 8 8HR and its maternal line, Wistar kiwid rat C (hereinafter referred to as "rwicy rat"), were treated with POA 1.
”/w% feed (MFi Oriental Yeast l
POA in plasma and thoracic aorta after 4 weeks of rearing in
Elbow examination was performed for concentration and platelet aggregation ability.

(1) Fatty acid analysis A homogenate (6%) of the extracted thoracic aorta was prepared using an all-glass homogenizer with a 19-fold volume of 1.15% aqueous potassium hydroxide solution.

Plasma or tissue homocyne) 0.1 ml! was placed in a centrifuge tube with a stopper, pentadecanoic acid gQm1cro-9 was added as an internal standard, and then chloroform-methanol solution (2
:1) 8ml! was added to perform protein removal and total lipid extraction. After centrifugation at 8,000 rpm for 10 minutes, the supernatant was transferred to a test tube with a screw cap and dried under a nitrogen stream at 40° C. or lower.

5% HCI! /methanol (Tokyo Kasei) at 0.2-0.
25m1! In addition, after capping, transmethylation was performed on an aluminum block at 100°C for 2 hours.

After cooling to room temperature - 1.0 ml of hexane! was added and stirred thoroughly to extract the fatty acid methyl ester into the hexane layer.Water tmt was subsequently added, and after gentle stirring, the mixture was centrifuged at 8,000 rpm for 6 minutes. The upper hexane layer was transferred to another test tube and dried with nitrogen gas. During analysis, hexane o,
i rrt and 1 to 8 at of them were subjected to gas chromatography analysis under the following conditions.

Gas chromatography device Shimadzu GC-4CM (FID) Column 8% 311ar IOCon Cromoso
rb W-HP80-100 mesh, 6mmX2m
Glass column temperature Inlet and detector; 280' column: 160
→220°C, 6°C/min Carrier Nitrogen gas 50mJ/min detection FID integrator YHP 8890A The results are shown in Table 7.

The ratio of POA to total fatty acids in plasma was significantly higher in the POA-administered group than in the control, indicating that POA absorption was good. Also, total fat in the thoracic aorta -
The ratio of POA to control is
It was significantly higher in the treated group, and the concentration of POA in the thoracic aorta was higher than the concentration in plasma. This is consistent with the fact that POA has a high affinity for the aorta and its stroke preventive effect is based on vascular reinforcement.

(2) Horn turbidimetry, which is widely used in the evaluation of antiplatelet drugs for platelet aggregation [Nature 194:927. (1962)). That is, 8.8% citric acid 8 to venous blood 9
Blood was collected while mixing sodium at a ratio of 1 part to 200 JF.
, centrifuged for 15 minutes. The supernatant part of the separated blood is plasma containing many platelets (Plitelet rich).
After fractionating the plasma (hereinafter abbreviated as "PRPJ"), the precipitated portion was further heated to 800.p.

Centrifugation was performed for 16 minutes, and the supernatant was collected to obtain platelet-free plasma (P1ata4st poor plasma).
mm.

Hereinafter, this will be abbreviated as rPPPJ). PIP to PPP
The platelet count was adjusted to 400,000 cells/ul by diluting the sample (this is referred to as the "rPRP sample").

Platelet aggregation was measured using an Alibometer (manufactured by Niko Bioscience ■). That is, put a 200μ PRP sample into a cuvette, set it in an alibometer, and heat it at 87°C.
After incubation for 1 minute, adenosine diphosphate (ADP), collagen, or Ca-iono7ar (A28187, manufactured by Sigma) was added as a platelet aggregation inducing agent, and changes in light transmittance were continuously recorded. The maximum aggregation rate of each was determined using the following formula, and the results are shown in Table 8.

A Snow-AI Relative transmittance of Al:PRP sample Ai: Relative transmittance of PPP ＾舅；PR with added aggregation inducing agent? Relative transmittance of sample From the results in Table 8, the following became clear.

That is, there is a difference between the POA administration group and the control group.
No difference was observed in the inhibition of platelet aggregation by P, collagen, and A28187. This indicates that the stroke preventive effect of POA is not based on the platelet aggregation inhibitory effect.

Test Example 4 All of the active ingredient compounds of the present invention have extremely low toxicity, such as undecylenic acid and norbonic acid LD.
The 60 values are as follows.

Undecylenic acid z, 5y/Kt;t (rat, oral) Palmitic acid 57±8.4 rap/Kf (mouse, intravenous) Formulation Example 1 Tablets each having the following composition are prepared.

POA 140ff1. F Starch 81.4 m, F Lactose i g 5 mg Polyvinylpyrrolidone 1.8 ml Magnesium stearate Tablets are prepared in the same manner.

Formulation example 8 POA 150.9 Avicel (trade name manufactured by Asahi Kaseikan) 40I cornstarch 801! Magnesium stearate 21 Hydroxypropyl methylcellulose 10g Polyethylene glycol-6000B, F Castor oil 4011 Methanol 401I After mixing and polishing POA, Avicel, cornstarch and magnesium stearate, tablet with sugar coating RIG mm kinematics. The obtained tablets are coated with a film coating agent consisting of hydroxypropyl methylcellulose, polyethylene glycol-6000, castor oil, and methanol to produce film-coated tablets.

Formulation Example 4 Undecylenic acid 150I Citric acid 1. Ol, lactose 88.5JF dicalcium phosphate 70. Of' Pull C1 2''7 F-6880, OJF Sodium Lauryl Sulfate 15.0.9 Polyvinylpyrrolidone 15.
OIi Polyethylene glycol (Carbowax 1500) 4.5. SF polyethylene glycol (Carbo"7'/Cus 6000) 46. OJF Cornstarch 80. OJF Dry Sodium Lauryl Sulfate 8.0 JF Dry Magnesium Stearate 8° OI Ethanol Appropriate amount Undecylenic acid, citric acid, lactose, dicalcium phosphate, Pluronic Mix F-68 and sodium lauryl sulfate.

The above mixture is screened through a positive 60 screen and wet granulated with an alcoholic solution containing polyvinylpyrrolidone, Carbowax 1500 and 6000. Add alcohol if necessary to make the powder into a paste-soft mass. Add cornstarch and continue mixing until uniform particles are formed. Pass through a 11kLIO screen, place in a tray and dry in an oven at 100°C for 12-14 hours. The transfer particles are sieved through an 1I & 116 screen, mixed with dry sodium lauryl sulfate and dry magnesium stearate, and compressed into the desired shape using a tablet machine.

The core is treated with varnish and sprinkled with talc to prevent moisture absorption. A subbing layer is applied around the core. Apply varnish a sufficient number of times for internal use. Further subbing layers and smooth coatings are applied to make the tablet perfectly round and smooth.

Pigmented coatings are applied until the desired shade is obtained. After drying,
Polish the coated tablet to give it a uniform luster.

invention! The vascular reinforcing agent of the present invention has the effect of restoring vascular fragility, abnormal permeability, strengthening blood vessels, and preventing vascular aging, and is effective against various vascular disorders in humans and animals, such as various types caused by vascular fragility. It can be effective in preventing and treating bleeding. In particular, the drug of the present invention is effective against hypertensive vascular disorders, especially cerebrovascular disorders, and is suitable for the prevention and treatment of stroke. The above-mentioned active ingredients of the present invention are well absorbed from the intestinal tract and are stable in the blood, so they have a long duration of effect, have low toxicity, and can be taken for a long period of time.

[Brief explanation of the drawing]

Figure 1i1 shows feed 1. 5HR8PO when given II
2 is a graph showing the relationship between blood pressure and blood pressure. FIG. 2 is a graph showing the relationship between age (days) and blood pressure due to chronic administration of methionine. FIG. 8 is a graph showing the relationship between stroke incidence rate and survival days. Figure 4 (11 is a graph showing the effect of feeds I and ff on blood pressure, and bl is a graph showing the effect of feeds I and ff on the onset of stroke. , is a graph showing the influence on the survival rate of 5HR8P to which the active ingredient of the present invention has been given. Restraint May II, 1980 1, Indication of the case, 1981 Patent Application No. 59955 2, Name of the invention: Vascular reinforcement 3, Person making the amendment - 7. Relationship to the case: Patent applicant □゛ 1- Pa~゛Ko・' Otsuka Pharmaceutical Co., Ltd. 4, Agent 2 Hirano-cho, Higashi-ku, Osaka (7) 10 Sawa cD Tsuru Hill lt
No. 06-203-0941 (Main) No. 8, Contents of amendment Contents of amendment 1 Table 7 (and above) listed on page 29 of the specification Procedural amendment layer layer September 21, 1982 1 Display of the case 1982 Patent Application No. 59955 2 Name of the invention Blood vessel reinforcing agent 3 Person making the amendment Relationship to the case Patent applicant Otsuka Pharmaceutical Co., Ltd. 4 Spontaneity of the agent 6 Detailed explanation of the invention in the specification layer to be amended Contents of amendment in section 1: The phrase "intravenous" in line 12 of page 34 of the specification is corrected as follows. (Intravenous) Test Example 5 Changes in the physical and morphological properties of arterial blood vessels due to the administration of the fatty acid of the present invention were measured. Namely, 3-month-old 5HR-8P 1) Four animals in the 81 group were treated with undecylenic acid 1w/ After feeding 31 times with feed supplemented with w% and feed without additives (control), both groups received 1%
They were given saline as drinking water and grown for another 10 days at 11R. 2
After 4 hours of fasting, the hindlimb rats were decapitated and the aorta was removed. The removed aorta is 1j11! Cold saline solution (4℃) aerated with
, pH 7.4), and then immersed in the same solution at 4° C. for about 24 hours. Remove the adipose tissue around the blood vessels and remove the area immediately after the aortic arch by 5 m1.
It was collected as a front and back cross section specimen and used as a material for viscoelasticity measurement. Dynamic self-recording viscoelasticity measuring device (VER-100
A sample mounting tank (Model: Miki Engineering Co., Ltd.) was filled with physiological saline and maintained at a constant temperature of 37° C., and the specimen was mounted using a hook attached to the mounting section. A tension of 1 gram or 8 grams is applied to the specimen, and a minute forced vibration (3.
The dynamic viscoelasticity (dynamic modulus of elasticity (E'), dynamic viscosity (η')) that occurs when applying 10,30H2) was determined by the following formula: KΦA' ・Q E'-ΔQ-8 Where: ΔQ: Amplitude of forced vibration F: Frequency of forced vibration S Cross-sectional area of two samples e: Length of sample (effective length) K: Constant (97,9) A': Reading of meter E1 A": Meter EsI The value of bone marrow cultivation (E') was significantly higher in the undecylenic acid-treated group than in the control group. Also, the dynamic viscosity (η') The values of the undecylenic acid administration group were also higher than the control group under all tension and frequency conditions. From these results, it was concluded that the viscoelasticity of the arterial blood vessels of 5HR8P was reinforced by the administration of undecylenic acid. I understand.

Claims (1)

[Claims] ■ General formula [wherein: C=, C represents a single or double bond (cis form). m is 0 or 6, and n is 7 or 8. ] A vascular reinforcing agent characterized by containing a fatty acid represented by the following and its salt as an active ingredient.