JPH10287560A - Pharmaceutical composition - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a safe oral pharmaceutical composition for replenishing nutrients for physical fatigue, anorexia during or after diseases, nutritional disorders, pyrogenous marantic diseases, etc., and further for nourishment, robustness and improvement in weak constitution by combining two kinds of specific compounds. SOLUTION: This composition contains ubidecarenone and a vitamin B1 derivative. The vitamin B1 derivative is compounded in an amount of 0.2-10 pts.wt. (converted into vitamin B1 ) per pt.wt. of the ubidecarenone. The vitamin B1 derivative is thiamine or its salt, dicethiamine, fursulthiamine, etc., especially dicethiamine. The addition of taurine to the composition in an amount of 1-300 pts.wt. per pt.wt. of ubidecarenone is preferable from the point of effects.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention aims to develop a pharmaceutical composition having an effect of improving physical fatigue.

[0002]

2. Description of the Related Art Conventionally, physical fatigue, after illness, anorexia,
Various substances have been developed for the effects of nutritional supplementation for nutritional disorders, febrile wasting diseases, etc., nutrition tonic, improvement or recovery of frail constitution, etc., which have sufficient efficacy and high safety Is not known.

[0003] Ubidecarenone is known to have an effect of improving myocardial damage due to ischemia, an effect of improving reduced cardiac output, and an antagonistic effect of aldosterone on Na storage. It is also known that it is taken into mitochondria by oral administration. Based on these pharmacological actions, it has been used to improve edema, pulmonary congestion, liver swelling, angina symptoms, etc. due to mild and moderate congestive heart failure.

[0004] Vitamin B ₁ derivatives are also required when the demand for vitamin B ₁ is increased and ingestion from the diet is insufficient (eg, wasting diseases, hyperthyroidism, pregnant women, lactating women, severe physical fatigue). Replenishment and Wernicke encephalitis, beriberi impulse, neuralgia, myalgia, joint pain, peripheral neuritis,
It is used for gastrointestinal motor dysfunction such as peripheral nerve palsy, central nervous system disorders, myocardial metabolic disorders, and constipation.

[0005]

SUMMARY OF THE INVENTION An object of the present invention is to provide a pharmaceutical composition which can relieve physical fatigue and is safe even if taken for a long period of time.

[0006]

Means for Solving the Problems The present inventors have studied the results for the achievement of the object, when orally administered combination of ubidecarenone and vitamin B ₁ derivatives, improving energy metabolism in the cytochrome electron transfer system in mitochondria It has been found that they promote oxidative phosphorylation, improve oxygen utilization efficiency even under low oxygen conditions, and increase the ATP production rate. As a result, they have found that such a composition has an effect of restoring physical fatigue, and completed the present invention.

[0007] That is, the present invention is a pharmaceutical composition comprising ubidecarenone and a vitamin B ₁ derivative.

[0008]

BEST MODE FOR CARRYING OUT THE INVENTION In the present invention, a vitamin B ₁ derivative means thiamine or a salt thereof, dicetiamine, fursultiamine, thiamine disulfide, bisbenthamine, bisbutiamine, thiamine monophosphate disulfide, benfotiamine, sicotiamine Octiamine, prosultiamine and the like, and dicetiamine is the most preferable in terms of effect.

With respect to the mixing ratio of each component in the present invention, the vitamin B ₁ derivative is 0.2 to 10 parts by weight, preferably 0.5 to 10 parts by weight, in terms of the amount of vitamin B _{1 based on 1} part by weight of ubidecarenone. 3 parts by weight.

In the present invention, it is preferable that taurine is further added from the viewpoint of the effect. The amount of taurine is 1 to 30 parts by weight per 1 part by weight of ubidecarenone.
0 parts by weight, preferably 5 to 200 parts by weight.

The effective dose of ubidecarenone is 5 to 50 mg per day for adults, preferably 10 mg
g to 30 mg. Thiamine derivatives are 1 day 1mg~100mg adult in terms of vitamin B ₁ volume, preferably 5Mg～30mg. Taurine is one adult
10 mg to 3000 mg per day, preferably 50 mg
２０００2000 mg.

In the present invention, in addition to the above essential components, for example, water-soluble vitamins such as vitamin B ₂ , vitamin B ₆ , vitamin B ₁₂ , vitamin C, biotin, carnitine, pantothenic acid, nicotinic acid, vitamin A, vitamin E , Fat-soluble vitamins such as vitamin D, xanthine derivatives such as caffeine, crude drugs such as ginseng, ground yellow, minerals such as calcium and magnesium, and amino acids such as methionine and leucine, in a range that does not impair the effects of the present invention. Can be.

[0013] The oral composition of the present invention may be used as it is or, if necessary, with other known additives such as excipients (D-
Sugar alcohols such as sorbitol, D-mannitol, xylitol, sugars such as glucose, sucrose, lactose, fructose, crystalline cellulose, carmellose sodium, calcium hydrogen phosphate, wheat starch, rice starch, corn starch, potato starch, dextrin, β -Cyclodextrin, light anhydrous silicic acid, titanium oxide, magnesium aluminate metasilicate, etc.), pH
Preparations (citric acid, malic acid, sodium hydrogen phosphate,
Dipotassium phosphate, etc.), cooling agent (l-menthol,
Mint water, etc.), suspending agents (kaolin, carmellose sodium, xanthan gum, methylcellulose, tragacanth, etc.), antifoaming agents (dimethylpolysiloxane, silicone antifoaming agent, etc.), thickeners (xanthan gum, tragacanth, methylcellulose, dextrin) ), Dissolution aids (ethanol, sucrose fatty acid ester, macrogol, etc.), disintegrants (low-substituted hydroxypropylcellulose, carboxymethylcellulose calcium, croscarmellose sodium, hydroxypropyl starch,
Partially pregelatinized starch, binder (methylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, polyvinylpyrrolidone, gelatin, gum arabic, ethylcellulose, polyvinyl alcohol, pullulan, pregelatinized starch, agar, tragacanth, sodium alginate, propylene glycol alginate) Esters, etc.), lubricants (stearic acid, magnesium stearate, calcium stearate, polyoxyl stearate, cetanol, talc, hydrogenated oil, sucrose fatty acid ester, dimethyl polysiloxane, beeswax, beeswax, etc.), antioxidants (dibutyl) Hydroxytoluene (BHT), propyl gallate, butylhydroxyanisole (BHA), tocopherol, citric acid Etc.), coating agent (hydroxypropylmethylcellulose, hydroxypropylcellulose, methylcellulose, ethylcellulose, hydroxypropylmethylcellulose phthalate, hydroxypropylmethylcellulose acetate succinate,
Carboxymethylethylcellulose, cellulose acetate phthalate, polyvinyl acetal diethylaminoacetate, aminoalkyl methacrylate copolymer, hydroxypropylmethylcellulose acetate succinate, methacrylic acid copolymer, polyvinyl acetate diethylaminoacetate, shellac, etc., coloring agent (turmeric extract, riboflavin) , Titanium oxide, carotene solution, etc.), flavoring agents (aspartame, ascorbic acid,
Stevia, menthol, crude licorice extract, single syrup, etc.), surfactants (polyoxyethylene hydrogenated castor oil, glyceryl monostearate, sorbitan monostearate, sorbitan monolaurate, polyoxyethylene polyoxypropylene, polysorbates, lauryl sulfate Sodium, macrogol, sucrose fatty acid ester, etc.), plasticizer (triethyl citrate, polyethylene glycol, triacetin, cetanol, etc.), coloring agent, fragrance, etc. are mixed, and liquid, tablet, granule, Oral preparations such as powders, capsules, and dry syrups can be prepared.

[0014]

According to the present invention, it has become possible to obtain an oral preparation which is effective for recovery from physical fatigue.

[0015]

The present invention will be specifically described below with reference to examples and test examples.

Example 1 Ubidecarenone 1500 mg Dicetiamine 500 mg Taurine 100 g Vitamin B ₂ 25 g Vitamin B ₆ 250 mg Inositol 2500 mg Nicotinamide 1000 mg Anhydrous caffeine 2500 mg Distilled water with the above ingredients and sucrose 800 g, D-sorbitol 250 g, citric acid 25 g and poly 5 g of oxyethylene hydrogenated castor oil was added and stirred to make it uniform. Thereafter, the pH was adjusted to 2.7 with sodium citrate, and then distilled water was added to obtain a 5,000 ml solution.

Example 2 Ubidecarenone 400 mg Dicetiamine 400 mg Taurine 20 g Vitamin B ₂ 100 mg Hytamine B ₆ 100 mg Nicotinamide 400 mg Inositol 1000 mg Carnitine chloride 1000 mg Biotin 1500 μg Potassium aspartate 2000 mg Caffeic acid anhydrous magnesium 4000 mg Glucose calcium aspartate 2000 mg The above components, sucrose 280 g, xylitol 80
g, stevia (300 mg), polyoxyethylene hydrogenated castor oil (2 g) and sodium malate (10 g) were added, and the mixture was stirred to make the mixture uniform. Then, after adjusting the pH to 2.8 with citric acid, distilled water was added to obtain a 1000 ml solution.

Example 3 Ubidecarenone 1000 mg Dicetiamine 2000 mg Taurine 20 g Vitamin C 40 g Ferrous fumarate 3000 mg Vitamin B ₁₂ 6000 μg Folic acid 100 mg Calcium carbonate 20 g Magnesium carbonate 10 g Vitamin B ₂ 500 mg Nicotinamide 5,000 mg Vitamin B ₆ 3000 mg Vitamin B ₆ 1000 mg A 200,000 I.U. Pitamin D ₃ 20,000 I.U. Vitamin E 1000 mg The above components and sodium hydrogen carbonate 30 g, polyvinylpyrrolidone 50 g, light anhydrous silicic acid 40 g, magnesium stearate 3.2 g, polyethylene glycol 90 g,
After weighing 6 g of aspartame and 50 g of polysorbate 80, adding a small amount of fragrance, and mixing uniformly, tablets 30
There were no tablets.

Example 4 Ubidecarenone 300 mg Dicetiamine 200 mg Taurine 15 g Biotin 5000 μg Sodium pantothenate 500 mg Nicotinamide 300 mg Vitamin B ₂ 50 mg Vitamin B ₆ 50 mg Ginseng extract 6000 mg (conventional drug equivalent) Deer mushroom extract 100 mg (conversion of crude drug) Extract 2000 mg (converted amount of crude drug) Beef yellow extract 10 mg (converted amount of crude drug) Royal jelly 1000 mg Anhydrous caffeine 500 mg In distilled water, the above components and sucrose 140 g, D-sorbitol 50 g, sodium citrate 5 g, and polyoxyethylene hydrogenated castor oil 1 g Was added and stirred to make the mixture uniform. Then, the pH was adjusted to 4.2 with sodium benzoate, and distilled water was added to make a 500 ml solution.

Example 5 Ubidecarenone 500 mg Dicetitiamine 2000 mg Taurine 10 g Vitamin A 200,000 I.U.Vitamin D 10,000 I.U.Vitamin E 1200 mg Vitamin B ₂ 500 mg Vitamin B ₆ 500 mg Vitamin B ₁₂ 500 mg Vitamin C 12.5 g Nicotinamide 2000 mg Pantothenic acid Calcium 1000mg Folic acid 20mg Biotin 7500μg Carnitine chloride 5000mg Calcium carbonate 15g Magnesium carbonate 13g Iron sulfate 3500mg The above ingredients and lactose 250g, maltitol 10g, citric acid 50g, light anhydrous silicic acid 5g, magnesium stearate 2g, polyethylene glycol 10g and polysorbate 80 8g Was weighed, a small amount of fragrance was added, and the mixture was uniformly mixed to obtain tablets 500.

[0021] Example 6 ubidecarenone 3000mg dicethiamine 700mg taurine 200g Biotin 50mg sodium chloride carnitine 5000mg pantothenic acid 5000mg arsenide Bu glutamic B ₂ 500 mg Vitamin B ₆ 500 mg Nicotinic acid amide 3000mg Vitamin C 50 g anhydrous cafe above components in-5000mg distilled water and sucrose 1400 g, 200 g of D-sorbitol, 1.5 g of stevia, 20 g of polyoxyethylene hydrogenated castor oil and 35 g of citric acid were added and stirred to make them uniform. Then, the pH was adjusted to 2.8 with sodium citrate, and distilled water was added to obtain 10 l of liquid preparation.

Example 7 Ubidecarenone 300 mg Dicetiamine 200 mg Magnesium aspartate 2000 mg Calcium aspartate 4000 mg Vitamin B ₂ 100 mg Vitamin B ₆ 100 mg Vitamin B ₁₂ 2000 μg Taurine 60 g Anhydrous caffeine 1000 mg Distilled water with the above components and sucrose 480 g, D-sorbitol 100 g , 6 g of citric acid and 1 g of polyoxyethylene hydrogenated castor oil were added and stirred to make the mixture uniform. Thereafter, the pH was adjusted to 3.0 with sodium benzoate, and distilled water was added to make a 2000 ml liquid.

Test Example 1 Male Sprague-Dawley rats (average weight 250 g)
The animals were divided into 6 groups of 8 animals. The feed was commercially available F-2.
Feed was freely available, drinking water was given tap water, and the animals were preliminarily reared for one week.

After the preliminary breeding, the spontaneous locomotor activity at the time of no treatment was continuously measured for 24 hours using an animation (activity measuring device), and was set as a previous value. Immediately after the measurement of the pre-value, forced swimming was performed for 2 hours as an exercise load. Immediately after forced swimming, each subject was orally administered, and the locomotor activity for 24 hours was measured again by Animex.

As test subjects, a mixed solution of ubidecarenone + disetiamine + taurine, a mixed solution of ubidecarenone + disetiamine, a ubidecarenone solution, a dicetiamine solution, a taurine solution, and physiological saline were used.
The concentrations of ubidecarenone, dicetiamine and taurine in each aqueous solution were 6 mg / ml, 10 mg / ml and 1 mg / ml, respectively.
It was adjusted to 00 mg / ml. The dose was orally administered at a rate of 1 ml per kg of rat body weight.

2 before and after forced swimming load by each subject administration
Table 1 shows the total travel distance for 4 hours.

[0027]

[Table 1]

Test Example 2 A Sprague-Dawley male rat (average body weight 200 g) was subjected to an exercise (forced swimming) load test. The condition of the forced swimming load is that rats each have about 5-10% of body weight.
Was applied to the neck for 30 minutes once a day.

In the exercise load group (N = 8), forced swimming load was continuously performed for 12 days, and after the load, ubidecarenone + disetiamine + taurine mixed solution, ubidecarenone + disetiamine mixed solution, ubidecarenone solution, dicetiamine solution, Taurine solution and saline were freely selected and exercised from day 1 to day 12 of exercise load, and their total intake was calculated for each non-exercise group (N =
8) and a comparative experiment.

The ubidecarenone in each aqueous solution was 6%.
mg / ml, dicetiamine 10 mg / ml, taurine 100
The one prepared at mg / ml was used. FIG. 1 shows the solution intake of each subject in the exercise group and the non-exercise group in each group.

[Brief description of the drawings]

FIG. 1 is a diagram showing the solution intake of an exercise load group and a target group.

Claims (5)

[Claims] 1. A pharmaceutical composition comprising ubidecarenone and a vitamin B ₁ derivative. 2. The pharmaceutical composition according to claim 1, which is a physical fatigue recovery agent. 3. The pharmaceutical composition according to claim _{1, wherein the} vitamin B ₁ derivative is dicetiamine. 4. The method according to claim 1, further comprising taurine.
The pharmaceutical composition according to any one of claims 3 to 3. 5. The pharmaceutical composition according to claim ₁ , wherein the vitamin B ₁ derivative is 0.2 to 10 parts by weight in terms of vitamin B _{1 based on 1} part by weight of ubidecarenone.