WO2019016988A1

WO2019016988A1 - Composition

Info

Publication number: WO2019016988A1
Application number: PCT/JP2018/005201
Authority: WO
Inventors: 徳行直井; 忠司松岡
Original assignee: エンチーム株式会社
Priority date: 2017-07-18
Filing date: 2018-02-15
Publication date: 2019-01-24
Also published as: TW201907948A; JP2019019084A; JP6253837B1; CN109562131A

Abstract

Provided is a composition for improving atrophy of the hippocampus in the human brain, a composition for increasing the volume of the hippocampus in the human brain, or a composition for increasing the volume of the human brain, in which coenzyme Q10 and earthworm dry powder are employed as active ingredients. A reduction-type coenzyme Q10 is employed as the coenzyme Q10. By doing so, the present invention provides a composition that can be employed in the prevention or/and treatment of brain-related diseases, such as Alzheimer's disease, dementia, Parkinson's disease, myalgic encephalomyelitis, multiple system atrophy, etc. The present invention provides, in particular, a composition that can be employed in the prevention or treatment of atrophy of the hippocampus in the brain.

Description

Composition

The present invention relates to a composition for human consumption or a composition for human administration.

Conventionally, various diseases such as diseases related to the brain such as Alzheimer's disease, dementia, Parkinson's disease, myalgia encephalomyelitis and multiple system atrophy, or diseases on blood vessels such as varicose veins in the lower limbs and deep vein thrombosis Therapeutic agents that exist and that prevent or treat these diseases are being investigated.

For example, brain diseases such as Alzheimer's disease are greatly increasing with the aging of the population, and have become a global health problem to be addressed. With regard to this Alzheimer's disease, agents for preventing and treating amnesia have been proposed (see Patent Document 1). This patent document 1 describes an agent for preventing and / or treating amnesia comprising at least one selected from carnozic acid and rosmarinic acid or a physiologically acceptable salt thereof as an active ingredient, and experiments using mice. The results are shown.
However, there has been a need for more effective therapeutic agents for humans.

JP, 2006-199666, A

An object of the present invention is to provide a composition that can be used for the prevention and / or treatment of appropriate diseases in view of the above-mentioned problems.

The present invention is characterized in that it is a composition for improving atrophy of the hippocampus in the human brain, which comprises coenzyme Q10 and earthworm dry powder as active ingredients.

The present invention can provide a composition that can be used for the prevention or / and treatment of a disease.

Explanatory drawing by MRI image of horizontal section of Alzheimer's disease patient's brain before administration. The explanatory view by the MRI image of a horizontal section of the brain of a patient with Alzheimer's disease after administration.

The present inventors diligently studied the utilization of coenzyme Q10. Among them, we examined using it for prevention or treatment of diseases related to brain and diseases related to blood vessels. Here, although the cause of onset of Alzheimer's disease is not always clear, attention is paid to the point that the decrease in mitochondrial activity is also considered to be one of the causes.

Biosynthesis of adenosine triphosphate (ATP), which is called "living energy currency", involves three systems: glycolysis, citric acid cycle, and electron transfer system. Mitochondria are deeply involved in the citric acid cycle and the electron transfer system. Therefore, mitochondrial activity is very important for life maintenance and activity. A factor that reduces mitochondrial activity is the reduction of reduced coenzyme Q10.

Mitochondria are constantly exposed to oxidative stress by reactive oxygen species, but are protected from oxidative stress by antioxidants. On the other hand, reduced coenzyme Q10 is a component of the electron transfer system and also an antioxidant. Therefore, when the reduced coenzyme Q10 decreases, it is considered that the antioxidant activity is reduced to cause dysfunction in the mitochondria, and the efficiency of the electron transfer system is reduced to decrease the ATP biosynthetic activity.

In dogs with dementia, there is a report that coenzyme Q10 in the brain is decreased, and that the related mitochondrial activity is decreased. In addition, Patent Document 1 also describes that coenzyme Q10 is effective as an agent for the prophylaxis or treatment of amnesia by experiments using mice. These statements suggest that the activity of the mitochondria is reduced and the coenzyme Q10 in the brain is related to brain diseases such as Alzheimer's disease and the like. We expect therapeutic effects.

However, although the effectiveness in animal experiments has been suggested (see Patent Document 1), there is also a research report that in human clinical research, oxidized coenzyme Q10 did not show a remarkable improvement effect on Parkinson's disease. (Parkinson study group QE3 investigators, 2014), the effect of coenzyme Q10 on brain disease was not always clarified, nor was the efficacy of coenzyme Q10 alone shown.
Thus, a composition capable of preventing and treating diseases related to the brain, diseases related to blood vessels and the like has been still in demand.

The present inventors have found that inclusion of coenzyme Q10 and earthworm-derived material among various raw materials is useful for amelioration of diseases related to the brain and amelioration of diseases related to blood vessels, in particular, for the recovery of atrophied hippocampus. The present invention has been accomplished by examining the efficacy as a preventive agent or a therapeutic agent for the finding, especially hippocampal atrophy.

Hereinafter, a composition containing coenzyme Q10 (coenzyme Q10) and an earthworm-derived raw material will be described as an embodiment of the present invention.

The coenzyme Q10 may be either reduced coenzyme Q10 (ubiquinol) or oxidized coenzyme Q10 (ubiquinone), but is preferably reduced coenzyme Q10. These two coenzymes Q10 change from each other by the redox reaction. Reduced coenzyme Q10 is biosynthesized in vivo and is active. In recent years, reduced coenzyme Q10 has been industrially manufactured and can be taken orally. On the other hand, oxidized coenzyme Q10 is orally ingested in vivo exclusively by food or industrially manufactured supplements and medicines. The ingested oxidized coenzyme Q10 is absorbed in the intestinal tract, then converted to reduced coenzyme Q10 and utilized. Therefore, although coenzyme Q10 contained in the composition according to the present invention is preferably reduced coenzyme Q10, oxidized coenzyme Q10 may also be used.

Coenzyme Q10 may be raw powder or processed product. The processed products include, but are not limited to, powder products and liquid products. The coenzyme Q10 used in this embodiment is preferably in powder form.

The content of coenzyme Q10 (in particular, reduced coenzyme Q10) contained in the composition of a daily dose needs to be a therapeutically effective amount, and the coenzyme Q10 (in particular, reduced coenzyme Q10) itself The amount (100%) can be 50 mg to 800 mg, preferably 80 mg to 500 mg, and more preferably 100 mg to 300 mg. Furthermore, although the content of coenzyme Q10 contained in the composition is preferably 200 mg to 300 mg, it is more preferably 100 mg to 200 mg so that the dose can be easily adjusted, and for patients with severe symptoms It is preferable to set it to 300 mg to 500 mg. The amount of therapeutically effective coenzyme Q10 (especially reduced coenzyme Q10) means the daily dose necessary to suppress or reverse any mitochondrial damage

The earthworm-derived material can be a material obtained from earthworms, such as earthworm dry powder, earthworm extract, or earthworm extract. Earthworm dry powder (including earthworm freeze-dried powder) may be raw powder or processed product. The processed products include, but are not limited to, extract powder and extract powder.

Earthworm freeze-dried powder is a powder which is freeze-dried using earthworms (especially, red earthworms native to the West) as a raw material. The earthworm freeze-dried powder has an action of converting plasminogen in blood to plasmin to exhibit high fibrinolytic activity, and an action of directly dissolving fibrin involved in blood coagulation. Therefore, earthworm freeze-dried powder is a disease related to blood vessels, treatment of cerebral infarction, ischemic cerebrovascular disorder, diabetes, hypertension, prevention of thrombosis, increase of fibrinogenase and suppression of increase of platelet aggregation rate It is known to be effective. The earthworm freeze-dried powder contains a proteolytic enzyme extracted from edible red earthworms, and has a characteristic that its fibrinolytic activity is strong.

This earthworm freeze-dried powder may be of LR end I (LR end 1), LR end II (LR end 2), LR end III (LR end 3) sold by the applicant, or other companies. , LR end III (LR end 3) is preferable.

The content of the earthworm-derived material (particularly earthworm freeze-dried powder) contained in the composition needs to be a therapeutically effective amount, and can be 10 mg to 200 mg, preferably 10 mg to 100 mg, 20 mg to 80 mg is more preferable. Furthermore, although the content of the earthworm-derived material (in particular, earthworm freeze-dried powder) contained in the composition is preferably 60 mg to 100 mg, it is more preferably 10 mg to 50 mg so that the dose can be easily adjusted. Preferably, it is 100 mg to 200 mg for patients with severe symptoms. In addition, the amount of the therapeutically effective earthworm-derived material (particularly earthworm freeze-dried powder) means the daily dose necessary to partially dissolve the thrombus.

The proportion of earthworm-derived material (particularly earthworm freeze-dried powder) contained in the composition can be 0.1 times to 1.5 times, preferably 0.3 times to 1 times (equal amount) It is more preferable to make the ratio 0.4 times to 0.7 times, and approximately 0.5 times is preferable. In other words, the ratio of earthworm-derived material (particularly earthworm freeze-dried powder) contained in the composition can be 0.1 to 4 times the amount of coenzyme Q10, 0.2 to 3 times It is preferable that the ratio be 0.4 to 2 times.

The form of the composition can be selected from soft capsules, hard capsules, tablets, powders, granules, drinks and the like. The form of a soft capsule, a powder, and a granule is preferable, and the form of a soft capsule is more preferable. For example, the composition may be contained in a tube nutrient, such as by mixing the composition in powder form with the tube nutrient. Thus, the composition can be administered to patients who have difficulty taking orally.

The composition contains, besides coenzyme Q10 and earthworm-derived materials, materials useful for maintaining and improving health such as vitamins, minerals, carbohydrates, nutrients such as lipids, and / or antioxidants, and / or supplement materials, etc. May be included.

The composition is not particularly limited in handling, and can be appropriately handled such as food, supplement, or medicine. For example, the composition may be treated as a physician recommended supplement.

The composition is effective for the prevention or treatment of a disease relating to the brain (in particular, a disease of hippocampal atrophy), and functions as a pharmaceutical composition, a therapeutic agent, a preventive drug, or a composition for treatment / prevention for such a disease. . Diseases relating to the target brain include, but are not limited to, Alzheimer's disease, dementia, Parkinson's disease, myalgia encephalomyelitis, multiple system atrophy and the like. The composition is also effective for the prevention or treatment of diseases associated with blood vessels, and functions as a pharmaceutical composition, a therapeutic agent, a prophylactic agent, or a composition for treatment / prevention for such diseases. Diseases relating to blood vessels of interest include, but are not limited to, varicose veins or deep vein thrombosis.
Hereinafter, examples of the present invention will be described.

<Hard capsule>
As Example 1 of the composition of the present invention, a hard capsule containing coenzyme Q10 and earthworm freeze-dried powder was prepared as follows. That is, a general powder mixing machine is used for each component material including reduced coenzyme Q10 stabilized powder (manufactured by Kaneka Co., Ltd .: reduced coenzyme Q10 P30) and earthworm freeze dried powder (manufactured by limited company Shiraku: LR end III) The mixture was mixed in a hard capsule to prepare a hard capsule (preparation). The reduced coenzyme Q10 stabilized powder (P30) indicates that the powder contains 30% of reduced coenzyme Q10, for example, if 180 mg of reduced coenzyme Q10 stabilized powder is used. The reduced coenzyme Q10 contained is 60 mg.

Component amount of each component material in 1 capsule: reduced coenzyme Q10 stabilized powder (P30) 180 mg (of which reduced coenzyme Q10 is 60 mg), earthworm freeze dried powder (LR powder III) 30 mg, edible yeast ( Zinc, copper, selenium yeast) 10 mg, vitamin B1 10 mg, vitamin B2 5 mg, vitamin B6 5 mg, vitamin B12 20 mg, folic acid 0.1 mg, vitamin D3 0.6 mg, excipient 89.3 mg.

<Powder>
As Example 2 of the composition of the present invention, a powder containing coenzyme Q10 and earthworm freeze-dried powder was prepared as follows. That is, each component material including reduced coenzyme Q10 stabilized powder (P30) and earthworm freeze-dried powder (LR powder III) was mixed by a general powder mixer, and then it was made into powder (formulation).

Component amount of each ingredient material in one bag: reduced coenzyme Q10 stabilized powder (P30) 360 mg (of which reduced coenzyme Q10 is 120 mg), earthworm freeze dried powder (LR powder III) 60 mg, edible yeast ( Zinc, copper, selenium yeast) 20 mg, vitamin B1 20 mg, vitamin B2 10 mg, vitamin B6 10 mg, vitamin B12 40 mg, folic acid 0.2 mg, vitamin D 3 1.2 mg, excipient 120.6 mg.

<Soft capsule>
As Example 3 of the composition of the present invention, a soft capsule containing coenzyme Q10 and earthworm freeze-dried powder was prepared as follows. That is, each component material including reduced coenzyme Q10 stabilized powder (P30) and earthworm freeze-dried powder (LR powder III) is mixed by a general soft capsule mixer, and then filled into capsules and soft capsule preparation (formulation) And

Component amount of each component material in 1 capsule: reduced coenzyme Q10 stabilized powder (P30) 50 mg (of which reduced coenzyme Q10 is about 16.67 mg), Michalal versus powder (manufactured by Michalalbers) 30 mg, vitamin E 10 mg, 139.7 mg of rapeseed oil, 70 mg of Poem DO-100V (manufactured by Riken Vitamin Co., Ltd.), and 0.3 mg of soya lecithin. The Michal Albers powder is a earthworm dry powder manufactured by Michal Albers.

<Improvement effect of disease>
By taking any of the compositions (hard capsules, powders, soft capsules) of Examples 1 to 3, improvement of symptoms of patients with brain diseases such as Alzheimer's disease including dementia, improvement of symptoms of patients with varicose veins of lower extremities There was an improvement in the symptoms of patients with deep varicose veins. As a specific improvement example, an improvement example to hippocampal atrophy in Alzheimer's disease is shown.

The preparation prepared in <Example 1> was administered 4 capsules a day for 3 months to 2 patients diagnosed with Alzheimer's disease. Confirmation of the clinical effect was performed by analyzing MRI images of the brain taken before and after administration using VBM tutorial (SPM 8) which is brain image analysis software.

FIG. 1 is a horizontal MRI image of the vicinity of the hippocampus of the brain before administration of patient A (an 82-year-old male diagnosed with severe Alzheimer's disease with moderate hippocampal degradation), one of the patients. FIG. 2 is a horizontal MRI image of the vicinity of the hippocampus of the brain after administration of the patient A. From this MRI image, it can be confirmed that the hippocampus is larger after administration than before administration.

As a result of analysis using SPM8, it was confirmed that the hippocampal volume of the brains of two patients after administration was 12% to 9% larger than before administration. Thus, it was shown that the preparation (hard capsule preparation) prepared in Example 1 is effective to improve hippocampal atrophy of the brain of Alzheimer's disease patients.

The present invention is not limited to the present embodiment, and can be other various embodiments.

The present invention can be used in the fields of medicines, supplements, foods and the like.

Claims

A composition for improving hippocampal atrophy in human brain comprising coenzyme Q10 and earthworm dry powder as active ingredients.
A composition for increasing the volume of the hippocampus in the human brain comprising coenzyme Q10 and earthworm dry powder as active ingredients.
The composition for enlarging the volume of the human brain which uses coenzyme Q10 and earthworm dry powder as an active ingredient.
Contains coenzyme Q10 and earthworm dry powder,
The coenzyme Q10 is a reduced coenzyme Q10,
A composition for improving hippocampal atrophy of the brain.
Contains coenzyme Q10 and earthworm dry powder,
The coenzyme Q10 is a reduced coenzyme Q10,
Composition for increasing the hippocampal volume of the brain.