JPH05960A - Therapeutic agent for chronic fatigue syndrome - Google Patents

Abstract

PURPOSE:To provide the subject agent safe to use, containing, as active ingredient, an extract from 'ninjin yoeito' (a kind of galenical drug, containing correct as the essential component). CONSTITUTION:The objective therapeutic agent containing, as active ingredients, (1) 2.0-4.0 pts.wt. of carrot, (2) 3.0-5.0 pts.wt. of root of Angelica acutiloba, (3) 1.0-5.0 pts.wt. of Paeonia albiflora, (4) 3.0-5.0 pts.wt. of root of Rehmannia glutinosa, (5) 3.0-5.0 pts.wt. of rhizome of Atractylodes lancea, (6) 3.0-5.0 pts.wt. of fungus of Pachyma hoelen, (7) 1.5-3.5 pts.wt. of bark of Cinnamomum cassia, (8) 0.5-3.5 pts.wt. of root of Astragalus huantchy, (9) 1.0-3.5 pts.wt. of peel of Citrus unshu (10) 0.5-3.0 pts.wt. of root of Polygala tenuifolia, (11) 0.5-2.5 pts.wt. of fruit of Schizandra chinensis, and (12) 0.5-2.5 pts.wt. of root of Glycyrrhiza glabra. These ingredients are heated at 80-100 deg.C for 30min to 2hr using an amount of an extracting solvent (e.g. water, ethanol) 5-25 weight times the amount of 'ninjin yoeito' to obtain 'ninjin yoeito' extract, which is then made into a pharmaceutical preparation normally in such a form as to be capable of oral administration through a conventional technique, thus obtaining the objective preparation, which is administered daily at a dose of 0.3-10g divided in one to three portions peradult.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a therapeutic agent for chronic fatigue syndrome. More specifically, it relates to a therapeutic agent for chronic fatigue syndrome containing Ninjinyoeito extract as an active ingredient.

[0002]

2. Description of the Related Art Chronic fatigue syndrome (Chronic Fa)
(Tigue Syndrome, hereinafter referred to as CFS) is a disease of unexplained cause whose main symptom is general malaise for 6 months or more. In 1988, the definition was proposed by Holmes, etc. of the US Center for Epidemics as follows. (Annalas of Internal
Medicine, 1988, Volume 108, 387-3
89).

Definition of CFS : The following main diagnostic criteria (maj
or criteria) (1) and (2) are satisfied, 6 or more symptoms of the minor diagnostic criteria (diagnostic criteria) are observed, and 2 or more physical findings are observed. It is a disease.

A) Major diagnostic criteria
ria) (1) General malaise for 6 months or more and tiredness continue.

(2) Malignant tumors, autoimmune diseases, bacterial infections, fungal infections, parasitic infections, AIDS,
It is not a chronic mental disorder, neuromuscular disease, endocrine disorder, or alcohol dependence.

B) Sub-criteria
ria) (1) Symptoms Diagnosis Mild fever Pharyngeal pain Large lymphadenopathy with tenderness Muscle pain General weakness Long-term (24 hours or more) fatigue after mild exercise Headache Joint pain without inflammatory symptoms Neuropsychiatric symptoms (Visual abnormalities, sensory disorders, emotional disorders) Sleep disorders (2) Physical findings Items Fever (37.5 to 38.6 ° C in oral temperature) Pharyngitis Lymphadenopathy CFS patients have been reported mainly in Europe and America. .. However, there is currently no therapeutic agent for CFS, and establishment of an effective therapeutic agent and a therapeutic method is desired.

By the way, Kampo prescription is a drug which is widely used for a long period of time for various chronic diseases because it has relatively few side effects. Ninjinyoeito is also one of the Kampo prescriptions, and it is conventionally known that it is effective against physical fitness after illness, tiredness, loss of appetite, anxiety, and anemia. It is also known that Ninjinyoeito extract enhances the antitumor effect of tegafur (see JP-A-61-194031). However, it is not known that Ninjinyoeito extract is effective in treating CFS.

[0008]

The object of the present invention is to provide a CF
It is to provide an excellent therapeutic agent for S.

[0009]

[Means for Solving the Problems] As a result of studying various Kampo prescriptions, the present inventors have found that Ginseng Yoeito extract is
The present invention has been completed based on the finding that it is effective against FS. The composition (mass ratio) of the ginseng yoeito in the present invention is ginseng (2.0 to 4.0) and toki (3.0).
~ 5.0), peony (1.0 ~ 5.0), ground yellow (3.0 ~)
5.0), Shiroshu (3.0-5.0), Furei (3.0-)
5.0), cinnamon (1.5-3.5), Astragalus (0.5-)
3.5), Chen skin (1.0-3.5), distant (0.5-
3.0), Gomiko (0.5-2.5) and Licorice (0.
5 to 2.5), preferably ginseng (3.0), toki (4.0), peony (2.0 to 4.0), ground yellow (4.
0), Sakushu (4.0), Furei (4.0), cinnamon (2.0)
~ 2.5), Astragalus (1.5-2.5), Chen skin (2.0-
2.5), Enshi (1.5-2.0), Gomiko (1.0-
1.5) and licorice (1.0-1.5).

The ginseng yoeito extract can be manufactured as follows.

First, the weight ratio of ginseng yoeito is 5 to 25.
Double, preferably 8 to 20 times, the extraction solvent is added, and this is usually heated at 80 to 100 ° C. for 30 minutes to 2 hours to obtain an extract of Ninjin Yoeito. Water, a water-soluble organic solvent or a mixed solvent thereof is used as the extraction solvent. Ethanol is preferred as the water-soluble organic solvent.

Next, the extract is filtered or centrifuged to remove insoluble matter, and then concentrated by ordinary means, for example, concentrated under reduced pressure to obtain a concentrated extract, or by ordinary drying means,
For example, dried extract powder is obtained by vacuum drying, spray drying or freeze drying.

The therapeutic agent for CFS of the present invention (hereinafter referred to as the agent of the present invention) comprises the above-mentioned concentrated extract, dried extract powder, and capsules, granules, tablets, fine granules containing them.
It includes various preparations such as powders and liquids. These various preparations may be supplemented with usual pharmaceutical additives such as excipients and disintegrants such as lactose, starch, crystalline cellulose, carboxymethyl cellulose calcium, silicic acid anhydride, synthetic aluminum silicate, magnesium stearate, etc. It can be produced by a conventional method.

The drug of the present invention is usually orally administered to produce CF.
Used to treat S. The dosage depends on the patient's condition, age,
Although it does not vary depending on weight, etc.
The dry extract powder is 0.3 to 10 g per day, and this amount is usually administered at once or in 2 to 3 divided doses.

[0015]

[Effects of the Invention] The above-mentioned Holmes
7. According to the CFS diagnostic criteria such as the above, the ginseng yoeito extract fine granules of Example 3 were applied daily to 35 patients recognized as CFS 7.
The therapeutic effect was tested by oral administration (2.5 g per oral administration) in 3 divided doses of 5 g each.

Out of 35 CFS patients who received Ninjinyoeito extract fine granules continuously for 1 month or longer, 26 (74%) of them had an effective clinical effect. The administration period was about 1 month to about 9 months, and no obvious side effects such as liver damage and renal damage were observed. Therefore, the drug of the present invention is effective for treating CSF and can be safely used.

The clinical course will be described in more detail below by citing 7 cases out of the effective clinical cases.

[Case 1] A 21-year-old female, an office worker. A decrease in natural killer cell activity (hereinafter referred to as NK cell activity) and antibody-dependent cell-mediated cytotoxicity (hereinafter referred to as ADCC activity), which are indicators of cell-mediated immunity, was observed at the time of initial diagnosis, and lymph nodes were found as physical findings. Swelling, slight fever, and general malaise and insomnia were observed as subjective symptoms. Ninjinyoeito extract fine granules were administered from the time of the first medical examination. Approximately 1 month later, physical findings and improvement in subjective symptoms were observed, and after about 2 months, the symptoms disappeared and the administration was discontinued. The cellular immunocompetence test was reexamined 3 months after the first visit, and normalization of NK cell activity and ADCC activity was observed. The effects on the dosing schedule and typical diagnostic items are shown in Table 1. In addition, ++ in the table
The sign means that the symptom of the diagnostic item was extremely remarkable, the + sign means that the symptom was recognized, and the − sign means that the symptom disappeared (hereinafter, Tables 2 to 7). -2 use the same symbols for the table).

[0019]

[Table 1] [Case 2] A female patient, a student, 20 years old. Similar to case 1, swollen lymph nodes and general malaise were observed at the first visit.
Administration of an anti-inflammatory drug was performed first, but no improvement in symptoms was obtained. The reduction of NK cell activity and ADCC activity was observed, and administration of Ninjin-yoeito extract fine granules was started. The slight fever disappeared about 4 months after the first visit, and the normalization of the cellular immune function was recognized about 5 months later. After 8 months, the lymphadenopathy had disappeared. The drug was discontinued after confirmation of normalization of the cellular immune function, but no relapse of symptoms was observed even after discontinuation of the drug. The effects on the administration schedule and representative diagnostic items are shown in Table 2.

[0020]

[Table 2]

[Case 3] A 27-year-old female, an office worker. At initial diagnosis, decreased cellular immune function, enlarged lymph nodes,
General malaise was noted. Although the anti-inflammatory drug was administered for about the first 2 weeks, clinical symptoms did not improve, so
Ninjinyoeito extract fine granules were administered. Improvement of cell-mediated immune function was observed 2 months after the first visit, and physical findings and subjective symptoms were improved 4 months later. Table 3 shows the effects on the administration schedule and typical diagnostic items.

[0022]

[Table 3]

[Case 4] A 28-year-old female, housewife patient. At the first visit, decreased cellular immune function, enlarged lymphadenopathy, general malaise, and no improvement in symptoms due to anti-inflammatory drugs were observed. About 2 months after the start of administration of Ninjinyoeito extract fine granules (about 2.5 months after the first visit), the cellular immune function,
Improvement of clinical symptoms was observed. There is no recurrence of symptoms after the end of the medication. Table 4 shows the effects on the administration schedule and typical diagnostic items.

[0024]

[Table 4]

[Case 5] A 33-year-old female, housewife patient. Among the cell-mediated immunity tests, NK cell activity decreased, and lymphadenopathy, slight fever, general malaise and insomnia were observed. Since the improvement of symptoms cannot be obtained by the administration of anti-inflammatory drugs and sleeping pills,
Administration of Ninjinyoeito extract fine granules was started. About 3 months after the first visit, the NK cell activity was restored to the normal range, after which clinical symptoms were also improved. Table 5 shows the effects on the administration schedule and typical diagnostic items.

[0026]

[Table 5]

[Case 6] A 28-year-old female, housewife patient. At the first visit, symptoms such as decreased cellular immune function and enlarged lymph nodes were observed. Since the anti-inflammatory drug was ineffective, administration of Ninjinyoeito extract was started one month later. About 4 from the first visit
Improvement in NK cell activity was observed at 8 months, and ADC at about 8 months
Improvement in C activity and clinical symptoms was observed. There is no recurrence of symptoms after discontinuation of the medication. The effects on the administration schedule and typical diagnostic items are shown in Tables 6-1 and 6-2.

[0028]

[Table 6]

[0029]

[Table 7] [Case 7] A 23-year-old woman, an office worker. At the first visit, clinical symptoms such as decreased ADCC activity and enlarged lymph node were observed. Since the anti-inflammatory drug was ineffective, administration of Ninjinyoeito extract fine granules was started one month after the first medical examination. Clinical symptoms started to improve about 2 months after the first visit, and ADCC activity returned to the normal range about 4 months later, so the drug was discontinued about 5 months later. However, about 1 month after discontinuation, clinical symptoms such as enlarged lymphadenopathy, low-grade fever, general malaise and insomnia recurred, and a decrease in cell-mediated immune function was also recognized. Administration of hot water extract was resumed. Approximately 2 months after the administration was restarted, ADCC activity and lymphadenopathy were improved again. The effects on the administration schedule and typical diagnostic items are shown in Tables 7-1 and 7-2.

[0030]

[Table 8]

[0031]

[Table 9]

[0032]

EXAMPLES Next, the present invention will be described more specifically with reference to examples.

Example 1 Production of dried powder of Ginseng Yoei-to extract 4.0 kg of ginseng, toki, ground yellow, white syrup, and peony
2.0g each for peony, peony, cypress, distant, 2.5k for cinnamon
g, yellow currant 1.5 kg, and konjac and licorice 1.0 k each
To the mixed crude drug consisting of g, 310 liters of water was added and heated, and the mixture was extracted at 100 ° C. for 1 hour. Filter the extract to about 3
After concentration under reduced pressure to 0 liter, spray drying was performed to obtain 6.7 kg of dried ginseng extract powder.

Example 2 Production of Dry Extract Powder To the same mixed crude drug as in Example 1, 248 liters of ethanol / water mixed solvent (v / v: 20:80) was added, and the mixture was heated under reflux for 30 minutes for extraction. .. The extract was filtered and the solvent was distilled off under reduced pressure. The residue was dried under reduced pressure and pulverized to obtain 5.7 kg of dried ginseng yoeito extract powder.

Example 3 Production of Ginseng Yoei-to extract fine granules (prescription) Main drug (dry extract powder of Example 1) 89.3 parts by weight crystalline cellulose 4.7 parts by weight synthetic aluminum silicate 5 parts by weight stearic acid 1 part by weight of magnesium (operation) After thoroughly mixing the above-mentioned components and making the mixture into a plate-like product by a compression molding machine, pulverizing and granulating with an oscillator, sieving and sieving this into 1 g of ginseng nutrition A fine granule containing 893 mg of a dry extract powder of hot water was obtained.

Example 4 Production of Tablets (Formulation) Main drug (dry extract powder of Example 1) 60 parts by weight Lactose 18 parts by weight Corn starch 5 parts by weight Synthetic aluminum silicate 9 parts by weight Carboxymethyl cellulose calcium 7 parts by weight Magnesium stearate 1 part by weight (operation) 28 parts by weight of 99% ethanol was added to the above-mentioned main ingredient, lactose, corn starch and synthetic aluminum silicate, and after sufficiently kneading, pulverized and granulated by a power mill (manufactured by Dalton Co., Ltd.) and dried. Then, a granulated product was obtained. Carboxymethylcellulose calcium was added to this granulated material and mixed well, and magnesium stearate was further added and mixed, and this mixture was tabletted into 300 mg, and 180 mg of dried extract powder of Ninjin-yoeito was contained in one tablet. A tablet containing was obtained.

Example 5 Production of Capsule (Formulation) Main drug (dry extract powder of Example 1) 92.8 parts by weight Synthetic aluminum silicate 5.0 parts by weight Magnesium stearate 2.2 parts by weight (operation) Mix each component thoroughly and mix 36
A capsule containing 0 mg was filled in to give a capsule containing 334 mg of dried extract powder of Ninjin-yoeito in one capsule.

 ─────────────────────────────────────────────────── --- Continuation of the front page (72) Inventor Yuji Saito 1-3-18 Mimatsugaoka Nishi, Misato-cho, Ikoma-gun, Nara (72) Yoshio Tatsumi 4-chome, 4-chome, Tomobuchi-cho, Osaka-shi, Osaka issue

Claims (1)

Claims: 1. A therapeutic agent for chronic fatigue syndrome comprising a ginseng yoeito extract as an active ingredient.