JPS6259208A - Ubiquinone-containing medicine - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

Detailed Description of the Invention [Field of Application in Industry-1-] The present invention provides a coenzyme selected from a series of ubiquinones of coenzyme Q1 to Q10, preferably coenzyme Q
10 and dried brewer's yeast extract.

PRIOR ART AND THE PROBLEMS TO BE SOLVED BY THE INVENTION Dry, bitter-free brewer's yeast is a natural source of essential amino acids and vitamin B complexes. Generally, 1g of yeast contains about 40% protein and 0.12% of thiamine hydrochloride.
mg, riboflavin 0.04■, nicotinic acid 0.25+
Contains ng, pyridoxine and pantothenic acid.

Yeast also contains many enzymes (thymase, saccharase, maltase, etc.), nuclein and peptone, and many fatty compounds, especially ceroli
ne).

The peculiarity of brewer's yeast is that, in addition to providing a set of enzymes necessary for the biochemistry of the intestines, it makes the vitamin complexes contained in it easily available to the body. The presence of enzymes and vitamin B complexes, in the event of their deficiency, activates the glycolytic process, further increasing the energy supply to cells and tissues.

Although the production of ATP is based on glycolytic processes and oxidative phosphorylation, it should also be taken into account that oxygen utilization, as well as energy production at the mitochondrial level, is dependent on the presence of coenzyme Q10. It is.

Coenzyme Q10 is known biochemically as a redox component of the respiratory chain and its associated oxidative phosphorylation machinery.

Coenzyme Q10 plays an essential role in mitochondrial electron transport between flaboproteins and the cytochrome system in ATP production. Vitamin B
Deficiencies in coenzyme Q1o, as well as defects in enzyme systems related to glycolysis and oxidative phosphorylation, such as complex-dependent enzyme systems, have been manifested in different pathological conditions, primarily in the muscle energy system.

These conditions primarily occur in senescence, atherosclerosis, myocardial failure, insufficient cerebral vascularization, and in growth and muscular effort (muscular effort).
This occurs when the energy demand increases, such as during s).

Under all these conditions, as has recently been made clear (Mortens
Drugs Under Experimental and Clinical Research (S, A.) et al.
Expt! , Cl1n, Res, ) 1984; Polkers K, et al., International Journal on Vitamin Research (
10ternat, J, VIt, Res, ) 4O-3
80-1970), the exogenous contribution (exogen
ouscontribution) was found to be useful (International Symposium on the Biomedical and Clinical Aspects of Volkers K et al.
IVlnt, Symp, on the = 4 - Biomedical and Clnical
Aspects of Coenzyme Q)
, Munich (Mjnich 1983).

Therapeutic uses of vitamin B complexes, as well as yeast, are well known, especially the healing effects of coenzyme Q10 in myocardial failure, hypertension and post-infarction conditions, and in energetic muscles. Effects that favor performance have only recently been demonstrated (Biomedical and Clinical Aspects on Coenteam Q).
Cl1nical Aspects ofCoenzy
me Q), Volkers K, Yamamura G (Y
amamura G.), 3 volumes, Elsevier/North Holland Biomedical Press (Elsevl)
er/North Holland Biomedic
al Press), 1981).

In addition to mediating the biochemical interactions mentioned above, brewer's yeast absorbs these amino acids, fatty substances, and coenzyme Q10 through the intestinal tract.
Enzymes that facilitate the biosynthesis of can be provided.

The lipid solubility of coenzyme Q 10 and the role of amino acids such as tyrosine in its biosynthesis are indeed known, as is the difficulty in effectively absorbing coenzyme Q 1G orally.

Besides containing tyrosine among other amino acids, brewer's yeast is also rich in vitamins and fatty substances.

[Means for solving the problem] Combining Coenzyme Q 10 with brewer's yeast extract has a surprising effect on the intestinal absorption of Coenzyme Q+a as well as on the metabolic and energetic activities carried out by Coenzyme 010. It showed a synergistic effect.

In fact, the remarkable synergistic effect between yeast extract and coenzyme Q 10 is significant, both in adapting to prolonged muscular effort and in protecting the myocardium from the toxic effects of anoxia, and in the blood circulation of coenzyme Q 10. and was demonstrated in increasing tissue concentrations.

Therefore, the pharmaceutical composition of the present invention containing the combination of coenzyme Q 10 and yeast extract does not allow R-phase to occur based on previously known data, and from a simple addition of the effects of single components. The irresistible synergistic effect makes it possible to obtain unexpected pharmacological and therapeutic effects.

In any case, the validity of the present invention depends on the exactness of the biological mechanism of the above.
does not depend on

[Effects and Examples Co (1) Toxicity and Pharmacology Tests The low toxicity and good tolerance of Coenzyme Q 10 and dried yeast extract are well known.

To assess whether the LD50 for coenzyme Q 10 is affected by oral administration of yeast extract and conversely whether the LDso for yeast extract is affected by oral administration of coenzyme Q +a A study conducted in -7= showed that oral administration of a 1=2 mixture of two compounds to rats or mice at doses higher than 5 g/day resulted in no LD5.
It was confirmed that there was no change in 11.

Chronic toxicity studies were also carried out in rats by oral administration of 1 g/kg of a mixture of the two compounds in a ratio of 1:1.1:20.1:100 for 3 consecutive months, which showed that body weight and various blood colors were Any toxic effect on cumulative or blood chemical parameters is considered an intolerance symptom.
Renee Syoptoms) was also not specified.

(2) Oral absorption studies of Coenzyme Q 10 In these tests, the oral absorption of Coenzyme Q 10 was measured either alone or in combination with dried yeast extract. The study was carried out using male Wistar rats fasted for 12 hours, and measurements of coenzyme Q10 concentrations were made in the blood, heart, liver and kidneys at various times between 0.5 and 8 hours after administration. The dosage is Abe.
Abe K, et al. (Proceedings in International Symposium Biomedical
AND CLINICAL ASPECTON COENTEAMQ
IO(Proc, 10t, Symp.

Biomedical and Cl1njcal A
spec ts or Coenzy IIle QIO)
S Austin N Geneva 119 g +) was measured by gas chromatography.

The results shown in Table 1 demonstrate that the combination of dried brewer's yeast extract and Coenzyme Q IQ surprisingly improves the oral absorption of Coenzyme Q 1G. Both blood and tissue concentrations of coenzyme Q10 in groups of animals treated with the combination according to the invention were
Surprisingly, the values were higher than those measured in the group of animals receiving Coenzyme Q 10 alone.

Table 1 shows that coenzyme QIO (100 mg/k) was administered to rats.
g) alone or with dried brewer's yeast (2.5 g/kg)
Coenchyme when administered orally in combination with ”
The concentration of mu-Q10 in blood and tissues is shown.

,,, -10- (3) Testing muscle exercise Training to muscle exercise and to higher resistance to fatigue is associated with an increase in mitochondrial enzyme activity. The test was on a male Sprague-Dawley.
The rats were divided into groups, one group was a control group, the other group received muscle exercise for 7 or 30 days, while another group received Coenzyme Q 101. Og/kg - 2.5 g/kg of dry yeast, or the combination of the invention, were treated orally daily at the same dose prior to muscle exercise for 7 or 25 days. For muscle exercise, use the Rotarod
d) Apparatus) 120 minutes each day at 20 m/min. After 7 or 25 days, the animals were sacrificed and the gastrocnemius muscle was isolated, homogenized, and subjected to differential centrifugation.
Nol, Chem, ) 24B-6988-1971)
Mitochondrial enzyme activity was measured using a photoelectric spectrophotometer.

The results in Table 2 show that by treatment with coenzyme Q 10 and brewer's yeast, coenzyme Q
The results show that the increase in mitochondrial enzymatic activity is surprisingly greater than that manifested when administering +o or dried yeast extract alone, or that would be expected from a simple addition of the two effects. .

[Margin below] (4) Tests in myocardial anoxia In these tests, myocardial anoxia was induced in rats by intravenous injection of 1 unit/kg of pitrcssin. Pirecine-induced coronary spasm decreased myocardial oxygenation (oxygenatlon) and resulted in the appearance of typical asphyxial T waves on the electrocardiogram.

Selected groups of male Wistar rats were pre-treated with 5g/kg of Coenzyme Q+O or 7g/kg of Ig/kg.
It was orally administered daily for 2 consecutive days.

The other group received a combination of the two compounds.

Seven days after treatment, asphyxial T-waves appeared with the injection of pitrecin, and the T-waves remained unchanged in the group treated with yeast alone and decreased by about 50% in the group treated with coenzyme Q+O alone, whereas , Koen Team Q 1
In the group treated with 0 in combination with yeast, the T wave hardly appeared. Therefore, this study demonstrated a strong synergistic effect for the two components of the combination.

A major aspect of the invention relates to the prophylactic and therapeutic application of the combination of coenzyme Q 10 and yeast.

The present invention provides coenzyme Q1, preferably coenzyme Q
1G and beer dry yeast in a ratio ranging from 1=1 to 1:10000, optionally with the addition of vitamin B complex or 2 or other vitamins or salts and customary excipients. .

Next, the pharmaceutical composition of the present invention will be explained based on prescription examples prepared according to common pharmaceutical techniques, but the present invention is not limited thereto.

Formulation example 1 (tablets and capsules) Coenzyme Q 10 Brewer's yeast dry extract 10 mg
1.50 mg coenzyme Q 10 beer yeast dry extract 11 mg 300m
g Coenzyme Q 1G Beer yeast dry extract→
- 5mg 300mg Coenzyme Q +c Brewer's Yeast Dry Extract 150mg 300mg Coenzyme Q 10 Brewer's Yeast Dry Extract + 100mg 300mg Prescription Example 2
(Syrup and/or granules) Coenzyme Q 10 Brewer's Yeast Dry Extract 11 mg 200 mg+
Vitamin B+ 0.01+ng Vitamin 82
0.05mg Vitamin 86 0.05mg Vitamin B+2 0.01mg or Coenzyme Q +o+Dried Brewer's Yeast Extract 5m
g Su 200 mg+
Vitamin BI 0.01mg Vitamin 82
0.05mg Vitamin 86 0.05mg Vitamin B+2 0.01mg or Coenzyme Q IO + Brewer's Yeast Dry Extract 1,
Omg 200 m
g10 Vitamin B+ 5mg Vitamin 82 5mg Vitamin B61oLI1g Vitamin B+2 0.5mg Vitamin A 500 Ll, I.

Vitamin E 5n+g Vitamin C100U, I.

Vitamin D 100 U, l.

Patent applicant: Schielev Akchen Gesellschaft

Claims (1)

Claims: 1. A pharmaceutical composition with tissue metabolic activity for oral administration, comprising a coenzyme selected from the series of ubiquinones of coenzyme Q_1 to Q_1_0 or a mixture thereof, and a dry yeast extract. 2. The pharmaceutical composition according to claim 1, wherein the ubiquinone is coenzyme Q_1_0. 3. The pharmaceutical composition according to claim 1 or 2, wherein the yeast extract is preferably a dry brewer's yeast extract that does not contain bitter substances. 4. The pharmaceutical composition according to claim 1, 2 or 3, wherein the weight ratio of coenzyme Q_1_0 and dry yeast extract is in the range of 1:1 to 1:10000. 5. In humans to improve the oral absorption of coenzyme Q_1_0 and improve the metabolic activity of coenzyme Q_1_0 in cases of muscle fatigue, tissue anoxia, aging, and disorders associated with impaired intestinal biochemistry. and/or in solid, semi-solid or liquid form for oral administration in the treatment of animals.
The pharmaceutical composition according to item 1, 2, 3 or 4. 6. The pharmaceutical composition according to claim 1, 2, 3, 4 or 5, which is in the form of a capsule, dragee, tablet, granule, syrup or oral vial. 7. Method for improving oral absorption and metabolic activity of coenzyme Q_1_0 by combining with dry yeast extract.