JP7393036B1 - Method for producing a depression treatment containing Beni Rahma extract components - Google Patents

Abstract

[Problem] To provide a therapeutic agent for depression containing an extract component of Beni Lafuma. [Solution] The leaves of Apocynum Venetum, which contains hyperoside, isoquerrcitrin, quercetin, flavonoid glycosides, catechins, and aposcynins, are roasted and an extract powder is prepared. After culturing by inoculating the bacteria into the inoculation holes of the logs, the logs are buried in a cultivation bed using Asama sand and cultivated, so that the ash content is mainly composed of calcium and phosphorus and germanium. Reishi containing Reishi, selenium, and silicon is heated to high temperature for a long period of time and carbonized in almost oxygen-free conditions to create a carbide powder of Reishi, and the reishi is added to the powder made from Beni Rahma. A drug for treating depression that contains an extract of Beni Lafuma mixed with 1% by weight or more of turf carbide powder. [Selection diagram] None

Description

The present invention belongs to the technical field of a drug for treating depression, which is prepared by mixing powder of carbide reishi with powder containing extract components of Beni Lafuma.

Conventionally, Apocynum venetum (scientific name: Apocynum venetum), also known as red hemp (red lafuma) or wild hemp, is a perennial herb of the Apocynaceae family that is widely distributed in China. Because Lafuma is a plant, it is easily affected by the soil of the production area, climate changes, sunlight hours, rainfall, etc., and the content of ingredients and active ingredients varies considerably.
Currently, most of the raw materials used for Rafuma tea are white hemp or large-leaved white hemp, which is a substitute for (red) Rafuma, but the Rafuma used in the present invention is a red hemp called red hemp. It's about Lafuma. This red hemp lahma is produced in Lop Nor, and is rich in fiber and has been used like hemp.Its origin is Lop Nor in the Xinjiang region of China. It has been named ``Rabuma'' since then.
In China, Lafuma leaves have been used as a substitute for tea leaves since ancient times, and Lafuma tea is also used as a folk medicine for fever relief and other purposes. Furthermore, multiple research institutes in China have conducted repeated medical and pharmaceutical research on Lafuma leaf, which is used as a folk medicine, and have reported that it is effective for treating high blood pressure, heart failure, bronchitis, dropsy, etc. has been done. On the other hand, even in Japan, Lafuma tea is commercially available under the trade name, for example, Yanlong tea, and is attracting attention as a tea with various effects.

In addition, the present inventors have discovered that Rafuma extract, which is obtained by roasting red Rafuma leaves (hereinafter simply referred to as Rafuma) and extracting them using an ultrasonic extraction method, has an effect on brain serotonin (5-HT) and dopamine (DA). It has been found to have a stimulatory effect. This Lafuma tea is disclosed, for example, in Japanese Patent No. 3517318 (Patent Document 1), and the use of Lafuma leaf extract for the prevention and treatment of intestinal infections such as intestinal bleeding Escherichia coli is disclosed in Japanese Patent Application Laid-Open No. 10-167978. (Patent Document 2), and the flavonoid compound isoquercitrin is extracted by roasting mafura leaves and used as an antidepressant for depression (Japanese Patent Application Laid-open No. 2002-201139 (Patent Document 3)). This is disclosed.
Regarding the effects of rahma leaves, it is known in ``herbal medicine'' that it has sedative effects; improves sleep, diuretics, lowers blood pressure, improves heart disease, improves nephritis floaters, and protects the liver.

On the other hand, the carbonized reishi mushroom used in the present invention was obtained by inoculating and culturing the inoculation holes of logs as disclosed in Patent No. 3545290 (Patent Document 4) by the present inventors. Afterwards, the Reishi mushrooms, whose ash mainly consists of calcium and phosphorus and also contains germanium, selenium, and silicon, are embedded in a culture bed made of Asama sand and kept at high temperatures for a long period of time. , and is a carbide of Reishi mushroom that has been carbonized in an almost oxygen-free condition.
In order to improve the density and blood flow rate of capillaries, the inventors developed Reishi carbide whose ash mainly contains calcium and phosphorus and also contains germanium, selenium, and silicon. It has been found that it is effective to use it as a food additive or additive.

In other words, this food-derived reishi mushroom is safe for the human body, and even when used alone, it does not cause constipation and is effective against various conditions such as hypertension, angina pectoris, hyperlipidemia, diabetes, cerebral infarction, chronic hepatitis, and cirrhosis. It is effective against diseases, and when used as a skin cleanser, it increases blood flow and thickens hair, and when used as a cosmetic ingredient, it has the effect of improving facial skin. Since it is a dentifrice containing toothpaste ingredients, it has the effect of improving blood circulation in the gums.

Patent No. 3517318 Japanese Patent Application Publication No. 10-167978 Japanese Patent Application Publication No. 2002-201139 Patent No. 3545290

The present invention is a depression treatment drug that is safe for the human body and further improves the original effects of Lafuma by using extract components of red hemp leaves and adding charred powder of Reishi to this. An object of the present invention is to provide a manufacturing method .

In order to solve the above problems, the present invention provides flavonoid glycosides including hyperoside, isoquerrcitrin, and quercetin, as well as red raffa from Lopnor, which contains catechins and aposcynins. The leaves of Apocynum Venetum are roasted, the extract is extracted using an ultrasonic extraction method, and the extract is powdered .
On the other hand, Reishi charcoal powder is a special product, which is cultivated by inoculating it into the inoculation hole of a log, and then embedding it in the log in a cultivation bed made of Asama sand and cultivating it. Reishi mushrooms containing calcium and phosphorus as main components and germanium, selenium, and silicon are heated to high temperatures for a long period of time and carbonized in an almost oxygen-free condition to create a powder of carbide of Reishi mushrooms. This is a method for producing a drug for treating depression, in which 1% to 2% by weight of the carbide powder of Reishi mushroom is mixed into Apocynum Venetum powder.
Further, in more detail, the method for producing the anti-depressant drug contains an extract component of Red Lamina that can decrease noradrenaline among neurotransmitters in the brain and increase serotonin and its metabolite (DOPAC). This is a method for producing a drug for treating depression.

The effect of the present invention is that the leaves of Apocynum Venetum contain hyperoside, isoquerrcitrin, and quercetin, which are harmless to the human body, and flavonoid glycosides, catechins, and aposcynins. This is a depression treatment drug that is made by extracting the extract using the decoction ultrasonic extraction method and turning the extract into powder, and mixing it with 1% or more by weight of special reishi charcoal powder, which is also harmless to the human body, and is used for human use. It reduces noradrenaline and increases serotonin and its metabolite (DOPAC), a neurotransmitter in the brain, without any risk of depressants, and has a therapeutic effect equal to or greater than that of the conventional antidepressant imipramine.

The present invention provides a method for producing a depression drug that contains an extract component of Beni Rahma as the main ingredient of the depression drug, which is harmless to the human body. This invention is based on the discovery that the medicinal efficacy of red raffa, which originally had an antidepressant effect, can be further enhanced by adding grass charcoal powder (hereinafter referred to as reishi charcoal powder).

[Example 1]
Beni Rafuma extract (powder)・15.00mg/kg
Reishi charcoal powder: 0.15mg/kg (approximately 1% by weight)
Total: 15.15mg/kg

Here, the Red Lafuma extract is a red Lafuma that is produced in "Lop Nor" and is rich in fiber, and because its place of origin is "Lop Nor" in the Xinjiang region of China, it is called "Rabuma". However, since it is a powder extracted by roasting and dehydrating the leaves of Beni Lafuma, the actual dose was 15 mg/kg per 1 kg of rat body weight. Then, adjust the weight of Beni Rafuma extract according to the weight of the rat being tested.
On the other hand, reishi charcoal powder is cultivated by inoculating it into the inoculation hole of a log, then embedding it in the log in a cultivation bed using Asama sand, and cultivating it so that the ash content is reduced to calcium and phosphorus. Reishi mushroom powder containing germanium, selenium, and silicon as its main ingredients is heated to high temperatures for a long period of time and carbonized in an almost oxygen-free condition. The actual dose is 0.15 mg/kg per 1 kg of the rat body weight as the test subject, and the weight of the Red Raffa extract is adjusted according to the body weight of the rat subject. Reishi charcoal powder is known to improve capillary density and blood flow speed.

[Example 2]
Beni Rafuma extract...15.00mg/kg
Reishi charcoal powder: 0.30mg/kg (approximately 2% by weight)
Total: 15.30mg/kg

In Example 2, the amount of reishi charcoal powder in Example 1 was doubled to 2% by weight.

[Comparative example 1]
Comparative Example 1 is a control group in which no treatment is applied.

[Comparative example 2]
Imipramine・・・・・・15.00mg/kg (100% by weight)

Comparative Example 2 uses only imipramine, and uses imipramine, which is an existing commercially available antidepressant and is a tricyclic antidepressant. However, although imipramine is effective for general anti-depression, it is not effective for adolescent depression and is known to increase the risk of adverse events such as dry mouth, fatigue, and weakness. Side effects have been reported, including feeling of discomfort, decreased concentration, drowsiness, headache, dizziness, lightheadedness, constipation, and tachycardia.

[Comparative example 3]
Beni Rafuma extract...15.00mg/kg

In Comparative Example 1, the reishi charcoal powder used in Examples 1 and 2 was not used, and 15 mg of Red Lafuma extract powder was simply administered to 1 kg of rat body weight as a test subject. .

Here, the effects and effects of the above-mentioned [Example 1], [Example 2], [Comparative Example 1], [Comparative Example 2], and [Comparative Example 3] will be explained. First, we will observe the depressed state. It is known that the level of monoamines, a neurotransmitter in the brain, fluctuates with stress and depression, and by observing this, the degree of depression can be objectively determined. [Example 1], [Example 2], [Comparative Example 1] to [Comparative Example 3] were subjected to a fear conditioned stress test (Conditio fear test: swimming) to rats for a short period of 2 weeks and a long period of 8 weeks. The drug was administered to rats, and changes in monoamines, which are neurotransmitters, in the rat brain were investigated to observe the action and effects.
In the fear-conditioned stress test, rats are given fear conditioning (electric shock) periodically (every other day or every two days) to learn and memorize fear responses. The reagent is orally administered to the rats every day for 8 consecutive weeks, and changes in brain monoamine substances are recorded and compared at the 2nd and 8th weeks.
Note that the control group is a group (control) that does not receive a new treatment (a group that is not given a drug or a group that is given a placebo). That's true. In this experimental example, no drug was administered.

Monoamine neurotransmitters are known as noradrenaline, dopamine, and serotonin, and due to the importance of their functions, they are called the "three major neurotransmitters in the brain." Here is a brief explanation of the functions and characteristics of each. do.
(1) Noradrenaline is the "hormone of anger" that excites the nerves.It monitors unpleasant stimuli and plays a role in producing tension states such as alertness and attention, and "emotional stress states" such as anxiety and fear. .
When a person encounters a frightening or startling experience, the brain secretes noradrenaline, enters a fight-or-flight mode, and takes actions to end the stressful experience. When stress is repeated, the sensitivity of noradrenaline receptors in the brain increases, causing a hypersensitive attack-or-flight response to even the slightest stimulus. It is known that animals exposed to unavoidable stress for long periods eventually develop analgesic symptoms and stop acting to avoid stress.
Therefore, when the amount of noradrenaline increases, this is undesirable because the body becomes hypersensitive to attack/flight reactions even to trivial stimuli, and when there is a lack of noradrenaline, it causes lethargy, apathy, decreased motivation, and depression.

(2) Dopamine is a neurotransmitter present in the central nervous system that increases concentration and produces pleasurable feelings, and is involved in motor control, hormone regulation, motivation, pleasure, motivation, learning, etc.
A lack of dopamine leads to a decline in mental function, such as a loss of interest in things, and a decline in motor function. It is known that dopamine levels decrease rapidly in patients with Parkinson's disease. Conversely, excessive release of dopamine can cause schizophrenia (hallucinations, auditory hallucinations, paranoia, etc.), Tourette's syndrome (involuntary movements of the face and head, purring, and obscene language), and overeating. It has been known.

(3) Serotonin has the function of a "general conductor" in the brain that stabilizes the mind, and is not affected by arousal stimuli from the internal and external environments, and is not affected by rhythmic movements (walking, It is excited by chewing, breathing, etc.) and provides moderate tension (tension of anti-gravity muscles, tension of sympathetic nerves, etc.) during activities in the awake state.
Serotonin has the effect of suppressing the excessive activity of other nervous systems, reducing abnormal excitement, impulses, and anxiety. A lack of serotonin can lead to depression, panic attacks, and eating disorders. Furthermore, even after waking up, they are unable to create a state of alertness, and even after that, they become unwell, their emotional brakes fail, and they become more likely to become aggressive.
Furthermore, it is said that when a stressful environment lasts for a long period of time, serotonin is nearly depleted, making it difficult to suppress excitement, impulses, and anxiety. Serotonin, most of which is found in the pineal gland, a small endocrine gland in the brain, is the precursor to melatonin, which is secreted from there. Melatonin, known to regulate circadian rhythms, is a sleep-inducing substance and the brain's largest antioxidant. Melatonin is a brain hormone important for preventing dementia and for sleep.

(4) Here, DOPAC (3,4-dihydroxyphenylacetic acid) is known as a metabolite of dopamine, and DOPAC (3,4-dihydroxyphenylacetic acid) is produced when dopamine is oxidized by monoamine oxidase in the mitochondria of central or sympathetic nerve terminals. DOPAC, which is an intermediate metabolite produced in body fluids such as cerebrospinal fluid, is thought to be produced in the central nervous system (brain) or peripheral autonomic nervous system, and measurement of its concentration in cerebrospinal fluid can be used to diagnose and treat neuropsychiatric disorders. Useful for determining effectiveness. Among these, low levels are shown in patients with Parkinson's syndrome and Alzheimer's disease.
However, recently the existence of peripheral dopaminergic nerves and the production of dopamine in the kidneys have been demonstrated, and it has become clear that dopamine is also involved in blood pressure and sodium metabolism. Therefore, in the future, it is thought that measurement will become meaningful in diseases that cause hypertension and electrolyte abnormalities.

(5) In addition, 5-HIAA (5-hydroxyindole-3-acetic acid) is known as a major metabolite of serotonin, but 5-HIAA is a catabolic end product of the serotonin pathway, and 5-HIAA is (CSF), which is present in body fluids such as blood and urine, and the levels of 5-HIAA differ between normal people and cancer patients. Deficiency of sepiapterin reductase, a type of redox enzyme, causes low levels of 5-HIAA in the CSF, as well as bipolar disorder (manic depression) or attention deficit hyperactivity disorder (ADHD).

Here, (1) "Rahuma powder + Reishi charcoal powder (1%)" of Example 1 of the present invention, (2) "Same (2%)" of Example 2 of the present invention, and (3) Comparative example (4) Imipramine (conventional tricyclic antidepressant) of Comparative Example 2, (5) (1) to (5) of the control group of Comparative Example 1, The test rats were subjected to a fear conditioned stress test (swimming) and administered orally for 2 weeks and 8 weeks continuously, and the amount of change in monoamines, which are neurotransmitters, in the rat brain was investigated. I made a table of

上記[表1]で、比較例1の対照組、比較例2のイミプラミン組、比較例3の紅ラフマエキス組、実施例1、実施例2に対する短期（2weeks）及び長期（8weeks）投与による脳内モノアミン量の変化（単位：ng/g）の表である。
なお、[表1]でモノアミン系脳内神経伝達物質量の単位、ng/gであるが、ng（ナノグラム）＝10の－6乗mg＝10の－9乗g（10億分の1g）で、被検体のラットの体重1グラム中のモノアミン系脳内神経伝達物の量である。

In the above [Table 1], the brain after short-term (2 weeks) and long-term (8 weeks) administration to the control group of Comparative Example 1, the imipramine group of Comparative Example 2, the red lafuma extract group of Comparative Example 3, Example 1, and Example 2. This is a table showing changes in the amount of internal monoamines (unit: ng/g).
In addition, in [Table 1], the unit of the amount of monoamine neurotransmitters in the brain is ng/g, but ng (nanogram) = 10 to the -6 power mg = 10 to the -9 power g (1 billionth of a gram) This is the amount of monoamine neurotransmitters in the brain per gram of the rat body weight.

In the experimental results in [Table 1], the "control group" of Comparative Example 1 was either not prescribed anything or administered a placebo, but in this case, nothing was prescribed and a fear conditioned group was administered. These are the results of a stress test.Imipramine from the imipramine group in Comparative Example 2 has been known as a tricyclic antidepressant, but this drug is not effective for adolescent depression. , is known to increase the risk of adverse events.
On the other hand, "Rahuma 15 mg/kg" of Comparative Example 3, "Rahuma 15 mg/kg + Reishi charcoal powder 0.15 mg/kg (1%)" of Example 1, "Rahuma 15 mg/kg + Reishi charcoal powder" of Example 2 The Beni Rafuma used in the 0.3 mg/kg (2%) charcoal powder and the Reishi charcoal powder used in the present invention are harmless to the human body, and the inventor has been using them for a long time. It was safe.
As will be described later, it was confirmed that adding 1% or more of the reishi charcoal powder of Examples 1 and 2 was more effective than adding 15 mg/kg of Lafuma in Comparative Example 3.

(1) First, in [Table 1], the dopamine amount was 311 ± 46 ng/g in the control group of Comparative Example 1 at 8 weeks, and 243 ± 18 ng/g in the imipramine group of Comparative Example 2. The amount of dopamine in the combination of Rafuma leaf extract in Example 3 decreased to 274±27 ng/g, but the amount of dopamine in the combination of Rafuma leaf extract + 1% Reishi charcoal powder in Example 1 of the present invention and 2% in Example 2 was almost the same. Met.
In addition, dopamine metabolite (DOPAC) was also 1041 ± 25 ng/g in the control group of Comparative Example 1 at 8 weeks, 688 ± 26 ng/g in the imipramine group of Comparative Example 2, and 688 ± 26 ng/g in the control group of Comparative Example 3. The amount of dopamine decreased to 812 ± 51 ng/g, but the dopamine content of Lafuma leaf extract + Reishi charcoal powder 1% of Example 1 of the present invention was 705 ± 44 ng/g, and the same 2% of Example 2 was 809 ± 15 ng/g. The amount was about the same, so it wasn't affected much.
A lack of dopamine leads to a decline in mental function, such as a loss of interest in things, and a decline in motor function, but it is known that dopamine levels decrease quickly in patients with Parkinson's disease. Conversely, excessive release of dopamine can cause schizophrenia (hallucinations, auditory hallucinations, paranoia, etc.), Tourette's syndrome (involuntary movements of the face and head, purring, and obscene language), and overeating. It has been known.
Therefore, a moderate amount of dopamine is required, neither too much nor too little.

In [Table 1], the amount of noradrenaline was 1633±42 ng/g in the control group of Comparative Example 1 at 8 weeks, 994±53 in the Rafuma leaf extract group of Comparative Example 3, and the Rafuma leaf extract of Example 1. + Reishi charcoal powder 1% combination showed the same level of decrease as 957 ± 15 ng/g, and the Lahuma leaf extract + Reishi charcoal powder 2% combination of Example 2 was 1105 ± 33 ng/g and the imipramine combination of Comparative Example 2. showed a similar decrease.
Therefore, if the amount of noradrenaline is too low, it will cause lethargy, apathy, loss of motivation, and depression, but if the amount of noradrenaline is too high, it will be undesirable because it will cause a hypersensitive attack/flight reaction to even the slightest stimulus. In Table 1], if the amount of noradrenaline does not increase, there will be no hypersensitive attack/flight reaction and a favorable state will be achieved.

In [Table 1], the serotonin amount was 509 ± 34 ng/g in the imipramine group of Comparative Example 2, 479 ± 41 ng/g in the Lafuma leaf extract group of Comparative Example 3, and 479 ± 41 ng/g in the Lafuma leaf extract group of Example 1 at 8 weeks. A significant increase was observed at week 8 with 509±34 ng/g for Reishi charcoal powder and 493±12 ng/g for Lafuma leaf extract + Reishi charcoal powder in Example 2.
Therefore, serotonin has the effect of suppressing the excessive work of other nervous systems, and when the amount of serotonin is insufficient, it prevents depression, panic attacks, eating disorders, etc., and also helps maintain alertness even after waking up. It has the effect of being able to create emotions, act as a brake on your emotions, and prevent you from becoming aggressive.
In addition, for serotonin (5-HT) and its metabolite (5-HIAA), Lafuma leaf extract (roasted + ultrasonic extraction) of Comparative Example 3, Lafuma leaf extract + Lafuma leaf extract of Example 1 and Example 2 It was confirmed that both Reishi charcoal powder and imipramine of Comparative Example 2 had the same increasing effect.

According to the test results in [Table 1] above, the Lafuma group and Lafuma + Reishi charcoal powder group of Example 1 (1%) and the Lafuma group and Lafuma + Reishi Charcoal powder group of Example 2 (2%), It affects brain catecholamines (dopamine DA, noradrenaline NE, serotonin) and their metabolites (DOPAC), and its strength is almost the same as that of imipramine in Comparative Example 2, which is an existing antidepressant. It is effective even in a short period of time (weeks), and it does not carry the risks of the traditional antidepressant imipramine. Here, it is thought that by adding Reishi charcoal powder, whose ash is mainly composed of calcium and phosphorus and contains germanium, selenium, and silicon, blood flow in the capillaries will improve and brain activity will be activated. It will be done. Note that the effect of the present invention cannot be obtained with ordinary Reishi charcoal powder.
Regarding the amount of Reishi charcoal powder mixed, the addition of 1% Reishi charcoal powder in Example 1 (Example 1) worked in two weeks, and even if the percentage was increased beyond that, the effect did not improve. It was found that the effect was stronger than that of the combination containing 2% Reishi charcoal powder (Example 2), and from this result, it is clear that 1% or more of Reishi charcoal powder is sufficient.

Claims (2)

The leaves of Apocynum Venetum from Lopnor containing flavonoid glycosides containing hyperoside, isoquerrcitrin, quercetin are roasted to create an extract powder;
After inoculating the bacteria into the inoculation holes of the logs and cultivating them, the logs are buried in a cultivation bed using Asama sand and cultivated, and the ash content is mainly composed of calcium and phosphorus, germanium, selenium, And, by heating the Reishi mushroom containing silicon to high temperature for a long time and carbonizing it under almost oxygen-free conditions, a powder of carbide of Reishi mushroom is created.
1% to 2% by weight of the carbide powder of Reishi mushroom is mixed into the powder made from Beni Lafuma to decrease noradrenaline among brain neurotransmitters and increase serotonin and its metabolites (DOPAC). A method for producing a depression treatment drug containing an extract component of Beni Lafuma. 2. The method for producing a drug for treating depression containing an extracted component of Lafuma rubra according to claim 1, wherein the Lachma rubra contains catechins and aposcinins.