JPS6231684B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention is based on the following general formula The present invention relates to a treatment and prevention agent for photosensitivity for humans and animals, which contains coenzyme Q represented by: Coenzyme Q was discovered in 1957 by Crane of the University of Wisconsin from the mitochondrial lipids of cow hearts, and is also called ubiquinone. Coenzyme Q exists in nature with various numbers of n in the above general formula. Although the effects of coenzyme Q in vivo are still not completely known, it is generally thought to be a coenzyme involved in the electron transport chain within mitochondria, and activates cellular respiration, which is coupled with the production of ATP. It is thought that it plays an important role in increasing the energy levels and activating various tissues in the body. Therefore, various studies have been conducted on the application of coenzyme Q to medicines, and at present, coenzyme Q ₁₀ (n=10 in the general formula) is used as a therapeutic agent for congestive heart failure. The present inventors have intensively investigated the application of coenzyme Q to other medicines, and surprisingly discovered that it is effective in the treatment and prevention of photosensitivity.
This completes the present invention. Photosensitivity generally refers to an abnormal qualitative or quantitative reaction to light from the sun or artificial light sources such as tungsten bulbs, fluorescent lights, and color televisions, especially when exposed to intense light at work. Humans, especially welders, lighting workers, or outdoor workers, are susceptible to photosensitivity. Symptoms of photosensitivity in humans vary depending on the cause, but the main ones include various skin diseases such as various types of eczema, urticaria, erythema multiforme, erythema nodosum, and purpura. This photosensitivity is also seen in animals such as livestock and poultry. In other words, the symptoms that animals exhibit when exposed to sunlight include erythema, itching, and
This is a dermatitis that causes edema on the head, ears, and skin, and in severe cases, it can lead to coma and even death. Such photosensitivity can be caused by light alone, light plus external factors, or
Although it is broadly classified into those caused by light plus intrinsic factors, it is generally thought that the most common cause is caused by external factors. External factors currently include pharmaceuticals, cosmetics, disinfectants, certain plants, artificial sweeteners, pigments,
These include chemical substances contained in petroleum products such as coal tar, food, and feed. Specific examples of pharmaceuticals include sulfur drugs,
Examples include sulfonylurea agents as oral diabetes drugs, chlorothiazide agents as diuretic antihypertensive agents, phenothiazine derivatives as tranquilizers, antibiotics such as tetracycline, and antifungal agents such as gluceofulvin. In recent years, photosensitivity due to a foreign substance contained in chlorella has become a problem, but this foreign substance is likely to be heophobide, a decomposition product of chlorophyll. Conventionally, when treating such photosensitivity with drugs, antihistamines, tranquilizers, sunscreens, steroids, and active vitamins have been used.
Although coenzyme _Q is currently being used, there is currently no definitive treatment, and there has been a longing for the development of new therapeutic agents.
was found to be effective. Therefore, an object of the present invention is to provide a novel agent for treating and preventing photosensitivity that is effective for humans and animals. Coenzyme Q used in the present invention is usually produced by synthesis, but it can also be produced by fermentation. Coenzyme Q ₁₀ used in the present invention is a yellow or orange powder that is soluble in chloroform, benzene, carbon tetrachloride, acetone, and ether, but insoluble in ethanol, water, and methanol. Melting point is approximately 48℃
It is. Next, the results of a toxicity test for coenzyme Q ₁₀ used in the present invention are shown. 1 Acute toxicity (mg/Kg)

[Table] 2 Chronic toxicity Wistar rat male and female 6, 60, 600mg/Kg/
Oral gavage for 26 consecutive weeks; after 26 weeks,
As a result of general conditions, blood tests, urine tests, and morphological observations (macroscopic and histological), no differences were observed between the animals and the control group. As mentioned above, coenzyme Q used in the present invention is an extremely safe drug and can be administered continuously as a treatment and prevention agent for photosensitivity. At this time, the dosage of coenzyme Q varies depending on the type of photosensitivity and the degree of symptoms, but it is usually about 5 mg per day for adults.
~200mg. When administered as a prophylactic agent, coenzyme Q can be administered before or simultaneously with the administration of a substance that causes photosensitivity, such as a drug. That is, for example, for patients prone to photosensitivity caused by phenothiazine derivatives, it may be administered simultaneously with, or prior to, the phenothiazine derivative. When coenzyme Q is administered in the present invention, powders, tablets, granules, capsules, injections, suppositories,
Any dosage form may be used, such as a bulk preparation. These can be produced by conventional methods using conventional excipients. That is, when making a powder, it is adsorbed onto excipients such as magnesium carbonate, silicic anhydride, synthetic aluminum silicate, calcium phosphate, lactose, starch, crystalline cellulose, glucose, and hydroxypropyl cellulose. Tablets and capsules are prepared by conventional methods based on the powder produced by the above method. When making an injection, it is made into an aqueous solution using a nonionic surfactant in a conventional manner. 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). At this time, commonly used adjuvants such as propylene glycol and glucose may also be mixed. Furthermore, when administering to livestock such as cows and pigs, and poultry such as chickens, it is usually added to their conventional feed. The amount added to these feeds varies depending on the type of animal and the degree of photosensitivity symptoms, but is usually about 0.01 to 0.5%. It is also possible to inject directly into animals. Next, in order to explain the effects of the present invention, the results of experiments on animals will be shown. The present inventors investigated heophobide, a degradation product of chlorophyll, which is thought to be one of the causative agents of photosensitivity in humans and animals, in order to elucidate the mechanism of photosensitivity and investigate new therapeutic agents. We conducted experiments using rats. Experimental example Heophorbide [Pheophorbide a, manufactured by STRONG, COBB AND COMPANY INC., USA]
25 mg/Kg body weight was dissolved in 0.5 ml of dimethyl sulfoxide and injected intraperitoneally into about 200 g of female Wistar rats, and irradiated with light at 10,000 lux for 5 hours to produce photosensitivity rats. When this photosensitive rat was observed histologically and haematologically, it was found that red blood cells were destroyed, that is, hemolysis occurred. Therefore, it is thought that various symptoms of photosensitivity appear due to this hemolysis. That is, hemolysis causes a thrombotic phenomenon in the microcirculation system, which causes various skin diseases such as skin inflammation, and also has an adverse effect on the heart due to an increase in serum potassium. Therefore, by preventing this hemolysis, photosensitivity can be prevented. Therefore, in order to confirm this phenomenon, we conducted a hemolysis test using rat red blood cells. That is, a method for investigating hemolytic reactions using dialuric acid, an oxidizing agent [Weiss, F., et al.:
J. Nut., 65, 143 (1958)] and the absorption intensity at 415 nm. The results are shown in Table 1.

[Table] As shown in Table 1, the red blood cells of rats administered with heophobide and exposed to light were compared with those of controls (administered with heophobide, no light irradiation; light irradiation system; and no heohobide administered, no light irradiation system). Significant hemolysis was observed. From the above experiments, it seems that basically all that is needed to prevent photosensitivity is to prevent hemolysis. As a result of various studies on how to prevent hemolysis, it was found that coenzyme Q can prevent hemolysis.The results are shown below. That is, Table 2 shows the results of comparing the effects of coenzyme _Q10 on the stabilization of rat red blood cell membranes with and without light irradiation.

[Table] As is clear from Table 2, the addition of coenzyme Q ₁₀ prevents hemolysis. Next, to further confirm the above facts, coenzyme
We investigated the extent to which _Q10 has a protective effect on stabilizing red blood cell membranes in rats. Specifically, we investigated the influence of coenzyme _Q10 on the composition of each fatty acid in total lipids in red blood cell membranes. The results are shown in Table 3.

【table】

[Table] As is clear from Table 3, the fatty acid pattern does not change when coenzyme Q ₁₀ is added, but the fatty acid pattern changes significantly when no additive is added. The above experiments revealed that coenzyme Q prevents hemolysis, which is an important mechanism of photosensitivity. Therefore, it has been revealed that coenzyme Q is effective in treating and preventing photosensitivity. 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 into 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 onto 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 Carboxymethylcellulose calcium
10g Microcrystalline cellulose (Avicel) 40g Polyvinylpyrrolidone (K-30) 5g Talc 10g Total amount 100g Coenzyme Q ₁₀ was dissolved in acetone, and the solution was then adsorbed onto microcrystalline cellulose, followed by drying.
Corn starch, refined white sugar, and carboxycellulose calcium were mixed with this, 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) Total volume with 100ml distilled water 1000ml Coenzyme Q ₁₀ , Nitsukol HCO-60 , mix sesame oil and half of propylene glycol and heat to about 80℃.
To this was added a phosphate buffer and distilled water in which sodium chloride and propylene glycol had been dissolved in advance at about 80°C to make an aqueous solution with a total volume of 1000 ml. This aqueous solution was dispensed into 1 ml ampoules, which were sealed and sterilized by heating. Formulation Example 5 Capsules are produced in exactly the same manner as Formulation Example 1 except that coenzyme Q ₉ is used instead of coenzyme Q ₁₀ . Formulation example 6 Coenzyme instead of coenzyme Q ₁₀ in formulation example 4
An injection is produced in exactly the same manner as in Formulation Example 4 except that Q ₇ is used. Formulation example 7 Poultry feed Corn 62% Soybean meal 20% Fish meal 8% Alfamil 2% Bran 5.1% Calcium carbonate 0.6% Calcium phosphate 1.5% Salt 0.4% Vitamin A, D 0.1% Vitamin B 0.2% Minerals 0.02% Antioxidant Agent 0.03% Coenzyme Q ₁₀ 0.05% A feed for the treatment and prevention of photosensitivity for chickens, which is obtained by adding 0.05% of Coenzyme Q ₁₀ as described above to the above-mentioned conventional feed for young chickens. Formulation Example 8 0.1% coenzyme Q ₁₀ was added to a conventional concentrated cattle feed to produce a feed for the treatment and prevention of photosensitivity for cattle.

Claims (1)

[Claims] 1. General formula (In the formula, n represents an integer of 7 to 10.) A treatment and prevention agent for photosensitivity for humans and animals, which contains coenzyme Q represented by the following formula. 2. The agent for treating and preventing photosensitivity in humans and animals according to claim 1, wherein n is 10.