JPH0317043A - New acetylene compound and 5-lipoxygenase inhibitor and cyclooxygenase inhibitior containing the same - Google Patents

Abstract

NEW MATERIAL:A polyacetylene compound of formula I (R is -CH2OCOCH3 or formyl). EXAMPLE:2Z, 9Z-Pentadecadiene-4,6-diyne-1-yl acetate. USE:It is useful as a drug such as antiallergic, anti-inflammatory, or circulatory drug, because it has 5-lipoxygenase inhibitor and cyclooxygenase inhibitor activity. It can be orally given. PREPARATION:For example, crude drug, 'SAIKO', its original plant, MISHIMASAIKO (Bupleuram facatum L.) or a similar plant is extracted with a solvent such as hexane, and the solvent is distilled off. The remaining is fractionated by chromatography of cellulose column as a carrier using a solvent such as hexane as an eluent to collect the compound of the formula. In another process, a kind of polyacetylene is acetylated to give the subject compound.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Application Field] The present invention relates to polyacetylene compounds that have 5-riboxygenase inhibitory activity and cyclooxygenase inhibitory activity and are useful as medicines such as antiallergic agents.

[Prior Art and Issues] Arachidonic acid is an unsaturated fatty acid with 20 carbon atoms, and as it cannot be synthesized in the body of living mammals, it must be supplied externally, and is counted as one of the essential fatty acids. There is.

The metabolic pathway of arachidonic acid is called the arachidonic acid cascade, and representative examples thereof include the cycloxygenase system that synthesizes the prostaglandin series and the thromboxane series, and the boxygenase system that synthesizes the leukotriene series.

In recent years, due to pollution problems and environmental changes in Japan, the number of patients with allergic diseases such as bronchial asthma and hay fever is increasing.

Furthermore, due to the increase in the elderly population, the number of patients with circulatory system diseases caused by blood clots is increasing, which has become a major social problem.

Abnormalities in the metabolism of arachidonic acid are thought to be one of the causes of these diseases, and as mentioned above, 5-riboxygenase and cyclooxygenase are important enzymes of the arachidonic acid cascade. Inhibitors are thought to be useful as medicines to treat various pathological conditions based on abnormalities in arachidonic acid metabolism, such as inflammation, thrombosis, allergies, and asthma.

Therefore, searches and developments are underway for drugs that use 5-riboxygenase inhibition and cyclooxygenase inhibition as indicators.

[Means for Solving the Problems] The present inventors have been conducting extensive research in search of a compound that has 5-riboquinease, inhibitory action, and cyclooxygenase inhibitory action, which is effective for the treatment of diseases caused by abnormal arachidonic acid metabolism. .

As a result, we discovered the crude drug Saigo, which is widely used clinically, and its original plant, Bupleurumfa.
lcaLum L. ), or polyacetylene compounds contained in plants of the genus thereof, which have excellent 5-riboxygenase and cyclooxygenase inhibitory effects, have been discovered, and the present invention has been completed.

That is, the present invention is as shown below.

A novel polyacetylene compound (hereinafter referred to as the compound of the present invention) represented by the following formula I (wherein R represents -CI{sOcOcHs or a formyl group) and the novel polyacetylene compound as an active ingredient. and a cyclooxygenase inhibitor containing the novel polyacetylene compound as an active ingredient.

For example, the following methods can be used to obtain the compound of the present invention.

The compound of the present invention is obtained by extracting the herbal drug Saigo, its original plant Mishimasaiko, or its congenerous plants with at least one solvent selected from hexane, diethyl ether, petroleum ether, ethyl acetate, chloroform, acetone, methanol, and ethanol. The residue obtained by removing the solvent from the obtained extract is eluted with at least one solvent selected from hexane, diethyl ether, petroleum ether, ethyl acetate, chloroform, acetone, methanol, ethanol, acetonitrile, tetrahydrofuran, and water. As a solvent, Diaion IP-20, MCI gel C H P
Bolus volumers such as 20P Sephadex L
Subjected once or several times to column chromatography or high performance liquid chromatography using Sephadex such as H-20, reversed phase silica gel, silica gel, polyamide or cellulose as a carrier, and then subjected to thin layer chromatography or high performance liquid chromatography. A polyacetylene compound can be obtained by fractionating while checking the target component.

Furthermore, by acetylating certain polyacetylene compounds that can be obtained as described above,
Compounds of the invention can be obtained.

Acetylation in this case can be carried out according to a conventional method using a commonly used acetylating agent. For example, the target substance can be obtained by carrying out a reaction using acetic anhydride in pyridine.

Next, experimental examples will be given to show that the compound of the present invention has a 5-riboxygenase inhibitory effect and a 5-riboxygenase inhibitory effect, and is useful as a medicine such as an antiallergic agent, an antiinflammatory agent, and a circular drug. explain.

Experimental Example 1 (5-riboxygenase inhibition effect) RBLl cultured cells were mixed with lRl4E so that the ratio was 5XIO8 cells/1.
Suspended in 50% phosphate buffer (pH 7.4) containing DTA and 10% ethylene glycol, and after sonication,
0,OOOXG for 10 minutes, then IO5.000xG
The supernatant obtained by centrifugation for 60 minutes was used as a 5-riboquine enzyme preparation.

As a substrate, an acetone solution of loAM arachidonic acid, an enzyme preparation obtained by fermentation as described above, and a compound obtained in an example described later is placed in a test tube so that the final strength is 100 ~,
The reaction was carried out at 37°C for IO minutes.

As an internal standard, 0.25 M butyl-3.5-dinitrobenzoate IO- was added and n-hexane 1.8-
Extracted with. The amount of 5-4 {ETE in this was measured by high performance liquid chromatography [column; TSKgelODS
-80TM (manufactured by TOYO SODA), mobile phase: tetrahydrofuran: acetonitrile: 1% acetic acid (5
:5 :9), flow rate; Id/min, detection; ultraviolet light (23
5 hours)].

From this result, the inhibition rate was calculated using the following formula, and the 50% inhibition concentration was determined.

C − S inhibition rate (%) = − x I 0 0 C C: 5-tlET without containing the compound obtained in the example
Peak value of E (Uramasa based on internal standard) S: 5-HETE when the compound obtained in the example was added
Peak area (corrected by internal standard) The 50% inhibitory concentrations of the compounds obtained in the examples are shown in Table 1.

Table 1 <<50% inhibitory concentration on 5-riboxygenase>> From the above results, the 5-lipoxygenase inhibitory effect of the compounds of the present invention was confirmed.

Experimental Example 2 (Ncrooxogenase inhibitory effect) Microsomes (100ρ) prepared from rabbit kidney medulla in a test tube,
Final concentration 0.1M+. :Adjusted potassium phosphate buffer
jC (pH 7.5), final concentration [0. Tributophan adjusted to M, glutathione adjusted to a final concentration of 4 mM, hemoglobin adjusted to a final concentration of 0.25a+H, compounds obtained in the experiment, and reaction substrates (1-
"C) - Arachidonic acid (5XlO'dpm) was taken and the total amount was 200 AIfl.

After incubating for 15 minutes at 37°C, IN HCl 50
I added fly to stop the reaction. PQ' as a carrier
E 1 was added and extracted twice with 1 tttQ of ether. After condensing the extract with eIt, the reaction product was separated by TLC (developing solvent: chloroform/methanol:acetic acid-18:t:l).

Color was developed with iodine vapor, the portion corresponding to PGE was scraped off, and the radioactivity was measured using a liquid scintillation counter, and the inhibition rate was determined using the following formula.

C C: Radioactivity when the compound obtained in Example is not included S: Radioactivity when the compound obtained in Example is added As a result, the inhibition rate of the compound obtained in Example [and 2] is
The final concentration was 73% at 147M.

Furthermore, the inhibition rate of the compound obtained in Example 3 was 81% at a final concentration of 50 compounds.

From the above results, the cyclooxygenase inhibitory effect of the compound of the present invention was confirmed.

Next, an acute toxicity test of the compound obtained in the example was conducted using CR male mice, and there were no deaths due to oral administration of 19/jc9.

Next, the dosage and formulation of the compound of the present invention will be explained.

The compounds of the present invention can be administered to animals and humans either neat or with conventional pharmaceutical carriers. The dosage form is not particularly limited and may be selected and used as appropriate, including oral preparations such as tablets, capsules, tablets, fine granules, and powders, and parenteral preparations such as injections and suppositories. Can be mentioned.

In order to exert the desired effect as an oral agent, although it varies depending on the age, weight, and severity of the disease of the patient, it is usually necessary for an adult to administer the compound of the present invention at a weight of 9 to 59 kg per day. It seems appropriate to take them separately.

Oral agents include, for example, starch, lactose, sucrose, mannitol,
It is manufactured using conventional methods using carboxymethyl cellulose, cornstarch, inorganic salts, etc.

In addition to the excipients mentioned above, binders, disintegrants, surfactants, lubricants, fluidity promoters, flavoring agents, coloring agents, fragrances, and the like can be used in this type of preparation as appropriate. Specific examples of each are shown below.

[Binding agent codenbune, dextrin, gum arabic powder, geladine,
Hydroxyprobil starch, methylcellulose, sodium carboxymethylcellulose, hydroxyprobilcellulose, crystalline cellulose, ethylcellulose,
Polyvinylpyrrolidone, macrogol.

[Disintegrant] Starch, hydroxyprobil starch, carboxymethylcellulose sodium, carboxymethylcellulose calcium, carboxymethylcellulose, low substituted hydroxyprobilcellulose.

[Surfactant] Sodium lauryl sulfate, soybean lecithin, sucrose fatty acid ester, polysorbate 80.

[Lubricant] Talc, waxes, hydrogenated vegetable oil, sucrose fatty acid ester, magnesium stearate, calcium stearate, aluminum stearate, polyethylene glycol.

[Fluidity promoter] Light anhydrous silicic acid, dry aluminum hydroxide gel, synthetic aluminum silicate, magnesium silicate.

Moreover, the compound of the present invention is! I! ．． am, emulsion, syrup, or elixir, and these various dosage forms may contain flavoring agents and coloring agents.

In order to exert the desired effect as a parenteral agent, the compound of the present invention is usually administered o. t xg~l9
Intravenous injection, intravenous drip, subcutaneous injection, and intramuscular injection are considered appropriate.

This parenteral preparation is manufactured according to a conventional method, and diluents generally include distilled water for injection, physiological saline, glucose aqueous solution, vegetable oil for injection, sesame oil, peanut oil, soybean oil, corn oil, propylene glycol, polyethylene glycol, etc. can be used. Furthermore, a bactericide, a preservative, a stabilizer, and an emulsifier may be added as necessary.

In addition, from the standpoint of stability, this parenteral drug is frozen after being filled into vials, etc., and the water is removed using normal freeze-drying techniques.
It is also possible to reconstitute the limb preparation from the lyophilizate immediately before use. Furthermore, isotonizing agents, stabilizers, preservatives, soothing agents, etc. may be added as appropriate.

Other parenteral preparations include liquid preparations for external use, liniments such as ointments, suppositories for rectal administration, and the like, which are manufactured according to conventional methods.

EXAMPLES Next, the present invention will be explained in more detail with reference to Examples, but the present invention is not limited thereto in any way.

Example 1 8 kg of ground saiko was extracted 4 times with ether 50 (
A total of 200a of the solvent of the extract was distilled off to obtain 129.8Li of ether extract. This ether extract was subjected to column chromatography using silica gel, and eluted with n-hexane and successively increasing amounts of edyl acetate.

Fracnoyone (hereinafter referred to as fraction 8) eluted with n-hexane:ethyl acetate (95:5) 35
．． 7g and n-hexane:furacunyone eluted with edyl acetate (7:3) (hereinafter referred to as fracunyone B).
9. I got +9.

Furthermore, fraction 8 was subjected to medium pressure preparative chromatography using silica gel (45φ x 500. fraction (
Hereinafter, it will be referred to as Fraccitane C. ) 10.59 was obtained. Fraction C was separated into LO times by preparative chromatography (20φ×300..) using reversed-phase silica gel ODS.

After distilling off the solvent of Fraxi 1, which was eluted from 1401/jQ to 180- with methanol, under reduced pressure, it was applied to the same column, and eluted from 200-1 to 2 with methanol:water (8:2).
The solvent of the fraction eluted at 20,1j was distilled off under reduced pressure to obtain 20 pale yellow curved substances.

This pale yellow oily substance was determined to be 2Z,9Z-pentadecadiene-4,6-noin-1- by the physical and chemical properties shown below.
I decided it was oil acetate! 'S0 mass spectrum C 171-[t! o tII n -M S
m/z: Calculated value 258.16195 Actual value 258.16086 E l -M S m/z: 2 5 8 (M”l 8).2 1 5, 1 4 11
28,114,89.4 1 Infrared absorption spectrum ν::A'att-':
3024,2956,2928 28562236,
1746,1548.14621372 1228
1030 970 UV absorption spectrum 5ax”
n! n(logε): 284 (4.16). 268 (4
．． 25) 254 (4.08), 24 + (3.77) 2
2 9 (3.5 1). 2 1 4 (4.7 5),
207 (4.60) Proton nuclear magnetic resonance spectrum (δ l) [) min CDCI,) 0.89 (3H
,t,J=7.001-1z)1. 2 5 -1.
4 0 (6 1-1, m), 2. 0 4 (2
H. br. q, J = 7. 0 8 Hz) 2.0
8 (3H, s). 3.0 8(211,br.d,J =6.9 2+1
z), 4.8 2 (211.dd, J = 6.5 3,
1.5 61-1z)5. 3 9 (l I-1
dttJ=IO. 55.6.92.1.671-fz)
5. 5 2 (l H dtL J=IO.55,7.36.1.671-1z)5.8
8 (11-1, br.d, J = I O.9 5H
z), 6. 1 1 (1 1-1, rN J=10.95, 6.531-1z). Note that δ=6.
I. The signals at lppm and δ=5.68ppm could be assigned to hydrogen at the 2nd and 3rd positions, respectively, by decoupling. Also, cambling constant (J =
I I. 0 3 [−[z) to Z llI,! I decided to translate it.

Similarly, δ=5.39ppm and δ−5.52p
The pm signal has been assigned to hydrogen at the 9th and 10th positions by decoupling, respectively. Additionally, coupling constant (J=IO.55]]2) to 9 and I
It was decided that the configuration would be from O to Z.

3C-nuclear magnetic resonance spectrum (δ ppm in CDCl3): 1 4.0 4(q). 1 8.0 5(t). 2 0
．． 8 2(q)2 2.5 4(t). 2 7.2 1
(t), 2 8.9 7(t) 3 1.4 8(t).
6 2.4 0 (t), 6 4.5 9 (s) 7 0.
3 1 (s), 8 0.8 2 (s), 8 4. 3
9(s), 1 1 1. 8 3(d), 1 2 1
．． 9 7(d) 1 3 3.1 2(.j), 1 3
9.4 9(d) 170.67(s) Example 2 Fruccitane B obtained by column chromatography using silica gel in Example 1 was further subjected to medium pressure preparative chromatography (45φ x 500xm) using silica gel. and n-hexane:ethyl acetate (7:3) 1 2
A fraction eluted from 007 to 1400-1.29 (hereinafter referred to as fraction D) was obtained.

Fraction D was subjected to medium pressure preparative chromatography (22φ x 300xz) using silica gel, and benzene:
269- to 310- was eluted with ethyl acetate (15:l), and the solvent was distilled off under reduced pressure to obtain 0.619 of a pale yellow oil. This pale yellow oily substance was determined to be 2Z9Z-pentadediene-4,6-diynol based on the physicochemical properties shown below.

Specific optical rotation. [α]0 0° (c = 1.Q O, chloroform) mass spectrum C+sHt. O H R -M S ra/z: Calculated value 216.1514 Actual value -216. l510 E I -M S m/z: 2 1 6 (M'), 1 9 8 Infrared absorption spectrum ν CCI 4α-1=3620.3360
,3024,2956,2928.2860,2236
, 1756, 1466, 1416, 1380, 1292
,1250,1 026.966,920,902,6
88 Ultraviolet absorption spectrum λ +ma:' nM (fog
ε) = 3 3 8 (2.8 5). 3 1 5 (3.1
2), 284 (4.07), 26B (4.l7), 2
53 (4.0 1). 24 1 (3.74). 2 2
9 (3.5 2). 2 1 5 (4.5 7), 20
7 (4.48) Proton nuclear magnetic resonance spectrum (δ ppm in CDCl3): 0. 8 9 (3 H, t, J = 7.0 H
z), 1.37 (2H, m). 1.7 1(l H, br, s), 2 . 0 4
(2 H, ddd J = 7.4, 1.6, 0.8 Hz
), 3. 0 8 (2 1-1, dddd, J
=6.9, 1.7, 1.20.8Hz), 4. 4
1 (2 1-1, dd, J = 6.4, 1.
5 Hz). 5. 3 9 (l I-[.ttd,
J = I0. 6,6. 9. 1. 6 H
z). 5. 5 2 (I H, ttd, J=IO
．． 6, 7.4, 1.7Hz) 5. 6 0 (l } [ , dd
d, J=1 1.0, 1.6, 1.21-1z), 6
．． 21 (1 summer - 1, dt, J = 1 1
．． 0,6. 4Hz) 13c-nuclear magnetic resonance spectrum (δ ppn+ in CDCI,) 1 4.0 4(q), 1 8.0 5(L)2 2.
5 7(j), 2 7.2 1(t). 28.97 (t
). 31.48 (t), 6 1.0 3 (t), 6 4
．． 6 8(s), 7 0.9 5(s), 8 0.0
6(s). 8 3.9 8(s). 1 0 9.
5 0(d), 1 2 2.1 1(d), 1
3 3.0 6(d), 145.09(d) This 2Z,9Z-pentadecadiene-4,6-diyn-l-ol 75-ol 9 was dissolved in pyridine anhydride 2-, and acetic anhydride 0.5- was added and left to stand overnight with stirring, and then the reaction solution was poured into ice water to stop the reaction. This is extracted with ether, and this ether layer is sequentially extracted with 0. After washing with IN hydrochloric acid and saturated aqueous sodium bicarbonate, the ether layer was distilled off under reduced pressure to obtain a yellow foam. This was subjected to medium pressure preparative chromatography (22φxl00u) using silica gel and chromatography using n-hexane:ethyl acetate (10:1) to obtain 40 μm of a pale yellow oily substance.

The physicochemical properties of this pale yellow oily substance completely matched those of the compound obtained in Example 1.

Example 3 The compound obtained in Example 2, namely 2Z. 9 Z-pentadecadiene-4,6-diyn-l-ol 61■,
Dissolved in methylene chloride l5-, add manganese dioxide 3
501n9 was added and stirred for 16 hours. The reaction solution was filtered, and the filtrate was distilled off under reduced pressure to obtain a yellow oil. This compound was purified by medium pressure preparative ram chromatography (22φ x 30ozm) using silica gel and using n-hexane ethyl acetate (9:I) as the mobile phase, resulting in a pale yellow oily substance 52. 'I got l9. Based on the physical and chemical properties shown below, this yellowish oily substance is 2Z
,92-diene-4,6-diyne-pentadecanal.

Mass spectrum C+sl'l1so II R -MS mHz: Calculated value 214.13513 Actual value 214.1355 El-MS m/z 2 1 4 (M"), 1 9 9, 1 8 5, 1 7
11 5 7, [ 2 8, 1 1 5, 9 1.8
1.5 5 infrared absorption spectrum ν cc+4 equipment-
1:3024,2956,2928,2856,222
8.2136,1688.15981580,1466
,1408,[290,125 0,! 180.
1116,1086956.900 Ultraviolet absorption spectrum λ + H word” 7) z (log
ε) 3 1 4 (4.3 5), 2 9 5 (4.3
2), 2B4 (3.95). 278 (4.0 1). 2
6 3 (3.6 1), 2 4 8 (3.2 5),
2 3 0 (4.3 5), 2 2 0 (4.2 3)
Bouton nuclear magnetic resonance spectrum (δ ppm in CDCl3): 0.89 (3H, t, J=7.00Hz) 1.2 5-
1. 3 4 (4 14, m) 1. 3 8 (2
1-1, m), 2, 0 5. (2 H, Ldd
, J=7.37, 7.35, l. 53Hz) 3.1 3
(2H, d, J=7.2 6Hz), 5. 4 0 (
IH, dtt, J=10.53,7,00,1.661-1z),5
．． 5 6 (I H , dH J=10.53, 7.37.1.63Hz), 6. 3
9 (I H , dd J = 1 0.94 .8.26Hz), 6. 6
4 (l H, dt J=10.94, 1.27Hz), 10.10 (1}1, d, J=8.26}{z)
The signals at δ-6.39 Ppm and 6.64 ppm could be assigned to hydrogen at the 2- and 3-positions, respectively, by decoupling. In addition, coupling constant (J
= f 0 . From 9 4 1-[z), 2nd and 3rd place
The double bond at position was determined to be in the Z configuration.

Additionally, the signals at δ = 5.40 ppm and 5.56 ppm are the result of decoupling at position 9 and lO
I was able to attribute it to the hydrogen at position. Also, from the coupling constant (J = IO .5 3 k-12), 9α
And the double bond at position 0 was determined to be Z configuration.

13c-nuclear magnetic resonance spectrum (δ ppm in CDCl3): 14.04(q). 1 8.1 6(t). 22.54
(t), 27.27 (jin) 28.9 1 (t), 3 1.48 (t) 64.36 (
s), 69.4 1(s), 8 6.2 3(s
). 8 8.1 8(s) 121.32(d), 1
27.66(d), 1 3 3.6 5(d),
+ 4 0.7 4. (d) 1 9 1.1
7(d) Example 4 ■Corn starch 44, ■Crystalline cellulose 40g ■Carboxymethylcellulose calcium 5g ■Light silicic anhydride 0.5g■Magnesium stearate 0.59■Compound obtained in Example 1
Log total: 100 g According to the above recipe, ■ to ■ were mixed uniformly and compressed using a tablet machine to obtain one tablet of 200 M9.

One tablet contains the compound 20R9 obtained in Example 1, and adults should take 10 to 25 tablets in several doses per day.

Example 5 ■ Crystalline cellulose 84.59 ■ Magnesium stearate 0.59 ■ Calcium carboxymethyl cellulose 51 ■ Compound obtained in Example 2 tog Total 1 0 09 Mix ■, ■, and part of ■ uniformly according to the above recipe After compression molding, pulverize, add the remaining amounts of ■ and
Q tablets were obtained.

One tablet of this tablet contains the compound 20.9 obtained in Example 2, and an adult should take 10 to 25.2 doses per day in several doses.

Example 6 ■Crystalline cellulose 49.59 ■10% hydroxypropyl cellulose ethanol solution 35? ■Carboxymethylcellulose calcium 5g ■Magnesium stearate 0.59■Compound obtained in Example 3 Log total 100y Mix ■, ■, and ■ uniformly according to the above recipe, make a netting by a conventional method, and extrude into a mill. After drying and crushing, ① and ③ were mixed and compression molded using a key press to obtain 200 M9 tablets.

One tablet contains 20J! of the compound obtained in Example 3! 9, and adults should take IO to 25 tablets a day in several doses.

Example 7 ■Corn starch 34.59 ■Magnesium stearate 509 ■Carboxymethyl cellulose calcium 59 ■Light strength l [hydrosilicic acid 0.5 g ■Example l
10 liters of the compound obtained? Total: toog According to the above recipe, ① to ① were uniformly mixed, compression molded using a compression molding machine, crushed using a crusher, and sieved to obtain granules.

1 g of this migratory agent contained the compound i o o obtained in Example 1.
It contains m9, and adults can take 2 to 5 g per day in several doses.

Example 8 ■ Crystalline cellulose 559 ■ 10% hydroxypropyl cellulose ethanol solution 35 g ■ Compound obtained in Step 2 10 g Total 100 y According to the above recipe, ■ to ■ were mixed uniformly and made into a paste. After being granulated using an extrusion machine, the mixture was dried and sieved to obtain granules.

This granule 19 contains the compound 100 obtained in Example 2.
19, and adults should take 2 to 5 g per day in several doses.

Example 9 ■Corn starch 89.59 ■Light silicic anhydride 0 59 Compound obtained in Example 3 10
9 total 1009 Mix ■~■ uniformly according to the above recipe, 200
M9 was filled into a No. 2 capsule.

Each capsule contains 20m9 of the compound obtained in Example 3, and an adult should take 10 to 25 capsules in several doses per day.

Example 10 ■ Soybean oil 52 ■ Distilled water for injection 89.5! ? ■Soybean phospholipid 2,59 ■Glycerin 21? ■ Compound l2 obtained in Example 4 Total amount 100g ■ According to the above recipe, dissolve ■ in ■ and ■, and add ■
The solutions of (1) and (2) were added and emulsified to obtain an injection.

Claims (2)

[Claims] (1) A new polyacetylene compound represented by the following formula | ▲ Numerical formulas, chemical formulas, tables, etc. are available ▼ | (In the formula, R represents -CH_2OCOCH_3 or a formyl group.) (2) The following formula | ▲There are mathematical formulas, chemical formulas, tables, etc.▼ | (In the formula, R represents -CH_2OCOCH_3 or a formyl group.) A 5-lipoxygenase inhibitor whose active ingredient is a new polyacetylene compound represented by . (3) A cyclooxygenase inhibitor whose active ingredient is a novel polyacetylene compound represented by the following formula | ▲ Numerical formulas, chemical formulas, tables, etc. ▼ | (In the formula, R represents -CH_2OCOCH_3 or a formyl group.)