JPH0132804B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to a peptic ulcer treatment and prevention agent. For more details, use the following general formula (wherein n represents an integer of 9 to 11) The present invention relates to a peptic ulcer treatment/prevention agent containing coenzyme Q represented by the following formula as an active ingredient. Coenzyme Q was first discovered in bovine heart muscle by Crane et al. at the University of Wisconsin in 1957, and although its in vivo effects are still not completely known, it is generally used in the mitochondrial electron transport chain. It is thought to play an important role in activating cellular respiration, increasing ATP production in conjunction with it, and activating various biological tissues. Therefore, various studies and studies have been conducted on the application of coenzyme Q to medicine, but at present coenzyme Q ₁₀ , where n is 10 in the above general formula, i.e., ubidecarenone (2,3-dimethoxy-5-methyl-6
-decaprenylbenzoquinone) is used as a treatment for congestive heart failure. The present inventors have continued to conduct intensive training on the application of coenzyme Q to other medicines, and surprisingly discovered that it is effective in treating peptic ulcers such as gastric ulcers and duodenal ulcers. . There are various treatments for peptic ulcers such as gastric ulcer and duodenal ulcer, but the main ones include antacids such as baking soda, magnesium trisilicate, synthetic aluminum silicate, propantheline bromide, A typical example is a parasympathetic nerve blocker such as buscopan. However, these drugs have the following drawbacks. In other words, although antacids dramatically improve subjective symptoms, their effects are temporary, and rebound development due to neutralization of gastric acid increases the acidity of gastric juice, making symptoms worse. It is the cause. In addition, the use of parasympathetic nerve blocking agents is intended to inhibit the secretion of gastric acid and suppress aggressive factors, but it is contraindicated in patients with concurrent glaucoma, prostatic hyperplasia, heart disease, intestinal obstruction, or bladder neck obstruction. and
Its use is severely restricted because it is associated with side effects such as visual impairment, urinary disorders, and constipation. Therefore, the present inventors have conducted various studies on drugs that do not have the above-mentioned side effects and can be used for a long period of time, and have unexpectedly discovered that the coenzyme Q of the present invention can achieve the intended purpose, and have completed the present invention. It is something. In other words, when peptic ulcers such as gastric ulcers and duodenal ulcers are treated with drugs, long-term use is inevitable due to the nature of the disease, but coenzyme Q used in the present invention is an extremely safe drug and has almost no side effects. Therefore, it is optimal as a treatment and prevention agent for peptic ulcers. Therefore, an object of the present invention is to provide a novel agent for treating and preventing peptic ulcers that has no side effects and can be administered continuously for a long period of time. As the coenzyme Q used in the present invention, substances in which n is 9 to 11 in the above-mentioned general formula [] are used, among which ubidecarenone (2,3-dimethoxy-5-methyl-6 -decaprenylbenzoquinone) is the most commonly used. Coenzyme Q used in the present invention can be produced by either a synthetic method or a fermentation method. Ubidecarenone, a representative compound used in the present invention, is a yellow or orange-yellow crystalline powder.
It is easily soluble in benzene, acetone, and ether, but almost insoluble in water and methanol. Melting point is approximately 48°C. Next, the results of a toxicity test for ubidecarenone used in the present invention are shown. 1 Acute toxicity (mg/Kg)

[Table] No deaths at the above maximum dose 2 Chronic toxicity Wistar rats of both sexes 6, 60, 600mg/
Kg/day was administered orally for 26 consecutive weeks, and after 26 weeks, general conditions, blood tests, urine tests, and morphological observations (macroscopic and histological) were performed.
No difference from the control group was observed. As is clear from the results of the above-mentioned toxicity tests, coenzyme Q used in the present invention is an extremely safe drug and can be administered continuously as a peptic ulcer treatment/prevention agent. At this time, the dosage of coenzyme Q varies depending on the type of peptic ulcer and the severity of symptoms, but is usually about 5 mg to 1000 mg per day for adults. In the present invention, when coenzyme Q is administered, powders, tablets, granules, capsules, injections, suppositories,
Any dosage form may be used, such as a bulk preparation. These can be manufactured by conventional methods using conventional excipients. Specifically, when making a powder, it is adsorbed onto excipients such as magnesium carbonate, silicic anhydride, synthetic aluminum silicate, calcium phosphate, lactose, starch, microcrystalline cellulose, glucose, and hydroxypropylcellulose. and tablets,
When preparing capsules, they are prepared by a conventional method based on the powder prepared by the above-mentioned method. When making an injection, it is made into an aqueous solution using a nonionic surfactant using a conventional method. Examples of nonionic surfactants include hydrogenated castor oil ethylene oxide adducts (e.g. Nitsukol HCO, etc.), sorbitan fatty acid ester ethylene oxide adducts (e.g. Tween, etc.), alkylphenol ethylene oxide adducts, fatty acid ethylene oxide adducts, and sorbitan. Examples include fatty acid esters (eg, span). On this occasion,
Commonly used adjuvants such as propylene glycol and glucose can also be mixed. Next, in order to explain the effects of the present invention, the results of animal experiments will be shown. Experimental Example 1 Effect on cold restraint stress ulcers SD female rats (body weight approx. 180-200g, 8-
According to the method of Brodie and Valitski [Proc. Soc. The inhibitory effect of the test compound on the development was determined. The test compounds were 5% gum arabic serum and 0.6% Tween.
Emulsify at 80 and 200mg/Kg 30 minutes before stress load.
Administered orally. The results are shown in Table 2.

[Table] 2 Effect on indomesacin ulcer SD female rats (body weight approx. 180-200g, 8-
After fasting for 24 hours, indomethacin was suspended in 5% gum arabic serum and
mg/Kg was administered orally, and the inhibitory effect of the test compound on indometacin ulcers was measured. The test compound was emulsified with 5% gum arabic serum and 0.6% Tween 80, and was orally administered 30 minutes before administration of indomethacin.

[Table] The above experimental examples revealed that coenzyme Q, the compound of the present invention, has an excellent preventive effect against peptic ulcers and is useful as a therapeutic/preventive agent for gastric ulcers, duodenal ulcers, etc. . Furthermore, as mentioned above, coenzyme Q, which is a compound of the present invention, is a highly safe drug with almost no toxicity, so when this is taken into account, it is extremely useful as a peptic ulcer agent.Therefore, the value of the present invention is extremely high. It is expensive. Next, actual formulation examples according to the present invention will be shown, but it goes without saying that the present invention is not limited thereto. Formulation Example 1 Capsule Coenzyme Q ₁₀ 5g Microcrystalline cellulose 80g Corn starch 20g Lactose 22g Polyvinylpyrrolidone 3g Total amount 130g The above ingredients were granulated by a conventional method and then filled with hard gelatin capsules. Formulation Example 2 Powder Coenzyme Q ₁₀ 50g Microcrystalline cellulose 400g Corn starch 550g Total amount 1000g Coenzyme Q ₁₀ was dissolved in acetone, then adsorbed on microcrystalline cellulose, and then dried. This was mixed with corn starch and made into a powder using a conventional method. Formulation example 3 Tablet Coenzyme Q ₁₀ 5g Corn starch 10g Refined white sugar 20g Carboxymethyl cellulose calcium 10g Microcrystalline cellulose 40g Polyvinylpyrrolidone (K-30) 5g Talc 10g Total amount 100g Dissolve Coenzyme Q ₁₀ in acetone, then dissolve the solution was adsorbed onto microcrystalline cellulose and then dried.
Corn starch, refined white sugar, and carboxycellulose calcium were mixed therein, and then an aqueous solution of polyvinylpyrrolidone was added as a binder, and the mixture was granulated by a conventional method. Talc was added as a lubricant to this, mixed, and then tableted into 100 mg tablets. Formulation example 4 Injection Coenzyme Q ₁₀ 10g Nitsukol HCO-60 37g Sesame oil 2g Sodium chloride 9g Propylene glycol 40g Phosphate buffer (0.1M, PH6.0) 100ml Total volume with distilled water 1000ml Coenzyme Q ₁₀ , Nitsukol HCO-60 , sesame oil and propylene glycol were mixed and dissolved by heating at approximately 80℃, and to this was added distilled water in which phosphate buffer, sodium chloride, and propylene glycol had been dissolved in advance at approximately 80℃, and the total volume was 1000ml. It was made into an aqueous solution. This aqueous solution was dispensed into 1 ml ampoules, which were sealed and sterilized by heating. Formulation Example 5 Formulation Examples 1 to 4 except that coenzyme Q ₉ or Q ₁₁ is used instead of coenzyme _Q 10.
Capsules, powders, and
Manufactures tablets and injections.

Claims (1)

[Claims] 1. General formula (In the formula, n represents an integer of 9 to 11.) A peptic ulcer treatment/prevention agent containing coenzyme Q represented by the following as an active ingredient. 2. The peptic ulcer treatment/prevention agent according to claim 1, wherein n is 10.