JPH11349487A - Woowhangchungshimwon composition of new recipe and its production - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a composition having the same or more activities to circulatory system, central nervous system and autonomic nervous system symptom such as blood pressure to which Woowhangchungshimwon is used, compared to the Woowhangchungshimwon containing moschus. SOLUTION: This composition contains Civet instead of moschus in a composition of a well known Woowhangchungshimwon composition constituted of 25 kinds of crude medicines such as Dioscoreae rhizoma, Glycyrrhizae radix, Ginseng radix, Typhae pollen, Massa medicata fermentata, Glycine semengerminatum, Cinnamomi cortex, Gelatinum, Paeoniae radix, Liriopis tuber, Scutellariae radix, Angelicae gigantis radix, Ledebouriellae radix, Atractylodis rhizoma alba, Bupleuri radix, Platycodi radix, Armeniacae semen, Hoelen, Cnidii rhizoma, Ampelopsis radix, Bezoar Bovis, Zingiberis rhizoma, Antelopis cornu, Borneolum and moschus.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a newly formulated beef yellow cinnamon composition, and more particularly to a known beef yellow cinnamon excluding a musk (musk), which is supplemented with a main ingredient of a known beef yellow cinnamon. And a method for producing the same.

[0002]

2. Description of the Related Art In modern society, life is becoming more complicated, and strokes, high blood pressure, heart disease,
The proportion of cardiovascular diseases such as psychogenic diseases is on the rise. Ushio Seishin is known as a herbal medicine that is effective in central nervous system diseases and autonomic nervous system diseases such as cardiovascular diseases, autonomic nervous system disorders, personnel afflictions, etc. It is the most useful and widely used in Chinese medicine, and is regarded as very important in the field of modern medicine.

[0003] Gyu Huang Seishingen is the first prescription recorded in the Taihei Keimin Japanese Pharmacopoeia, and is also recorded in the Chinese medicine books such as Dongbo-hoho, Introductory Medicine, Chinese Medicine, and in Korea in 1613. It was recorded for the first time in Higashi Medical Book, which was revised by Kondo. The prescription composition of Gyu Huang Qingshin is slightly different according to the literature, but the case of Korea is based on Dong-Imbo and herbal medicine. However, recently, among the herbal medicines of Gyu Huang Seishin, vermilion vermilion and Ishio Huang are each composed of heavy metals, mercury and arsenic, respectively, and were removed from Gyu Huang Qing Shin's prescription due to safety concerns. In accordance with the Convention on International Trade in Endangered Species of Wild Plants and Plants (CITES), raw materials have become difficult to receive and have been removed from the prescription (currently, Hen Qiu Huang Qing Shin Yuan, Yuan Fang Huang Qing Shin Yuan, half quantity Gyu Huang Qing Shin Yuan) Are used separately.)

[0004] According to the results of a re-evaluation of the drug on beef yellow spirit in 1992, the ingredients of the raw material of the original beef yellow spirit were in 100 pills or 100 bottles of liquid "26.3 g of Yamayaku, Licorice 1
8.8 g, Ginseng 9.4 g, Ganhuang 9.4 g, Kojiro 9.4 g, Soybean Yellow Roll 6.6 g, Cinnamon Bark 6.6 g, Glue 6.6 g, Peony 5.6 g, Bakumondo 5.6
g, Orgon 5.6 g, Toki 5.6 g, Windproof 5.6 g, White Aju
g, saiko 4.7 g, bellflower 4.7 g, apricot kernel 4.7 g, bukuryo 4.7 g, senkyu 4.7 g, beef yellow 4.5 g, trageram horn 3.8 g, musk 3.8 g,
It contains 3.8 g of dragon brain, 2.8 g of juniper, 2.8 g of ginger.
In the bottle “Yakuyaku 28.2 g, Licorice 20.2 g, Ginseng 9.7 g, Kamaboshi 1
0.0 g, Kamigoji 10.0 g, soybean yellow roll 7.0 g, cinnamon bark 7.0 g, glue 7.0
g, Shakuyaku 6.0 g, Mugiwinter 6.0 g, Ougon 6.0 g, Toki 6.0
g, windbreak 6.0 g, white jujube 6.0 g, saiko 5.0 g, bellflower 5.0 g, apricot kernel 5.0 g, bukuryo 5.0 g, senkyu 5.0 g, beef yellow 1.4 g, tragelapou horn 3.5 g, musk 0.5 g, dragon brain 4.1 g, juniper 3.0 g,
3.0 g of ginger, half the amount of raw material of beef yellow Qingdao is in 100 pills or 100 bottles of liquid.
g, ginseng 4.7 g, kabuki 4.7 g, koji malt 4.7 g, soybean yellow roll 3.
3 g, cinnamon 3.3 g, glue 3.3 g, peony 2.8 g, burmen winter 2.8 g, gongon 2.8 g, toki 2.8 g, windbreak 2.8 g, white jitsuju 2.8 g, saiko
2.3 g, bellflower 2.3 g, apricot kernel 2.3 g, bukuryo 2.3 g, sengyu
2.3 g, beef yellow 2.3 g, Tragelaphus 1.9 g, musk 1.9 g, dragon brain 1.9
g, juniper (1.4 g), and ginger (1.4 g).

[0005] The application of Gyohyo Seishin Gen pill / solution, Ganfu Gyohyo Seishin Gen pill / solution, and half the amount of Gyohyo Seishin Gen pill are the same as in the case of stroke. (Stroke, general paralysis, paralysis of the limbs, paralysis of the limbs, speech disorder, coma, mental disorder, facial paralysis, cerebral bleeding), hypertension, palpitations, respiratory confusion, mental anxiety, sudden / chronic convulsions, autonomic dysfunction, personnel incongruity Is mentioned.

[0006] The former dosage form of Gyu Hyo Seishin is a pill, which is manufactured using each herbal powder and honey. If stored for a long period of time, beef yellow Kishinshin pills become hard and difficult to take, and there is an inconvenience that they must be repeatedly manufactured as needed. However, at present, the use of excipients such as sodium carboxymethylcellulose has produced Ushio Seishin, which does not harden even when stored for a long period of time. Recently, some crude drugs such as mountain herbs have been extracted with water, mixed with fine powder of some crude drugs such as beef yellow and musk, and added with suspending agents, viscosity modifiers, etc. Yuan is manufactured.

[0007] On the other hand, musk, which is a main component in the original composition of beef yellow cherries, is a dried substance of incense sac in the abdomen of a male musk roe deer belonging to the deer family, and has a central stimulating action, a uterine stimulating action, and an antibacterial action. There is. In clinical practice, it is mainly used as a stimulant for the central nervous system for recessive consciousness disorders, seizures, strokes, etc. It is used as a blood circulation enhancer for bruising, swelling in the abdominal cavity, etc.

However, in accordance with the International Trade Agreement on Endangered Species of Wild Animals and Plants (CITES),
With the suspended international trade on musk being completely banned from October 1996, the shortage of musk, one of the essential medicines of Gyuhuang Seishin, is becoming more serious, and measures to address this are urgently needed. Is required.

[0009]

As a countermeasure to this problem, the present inventors have been included in the Korean Medical Book to develop a new prescription that can enhance the efficacy and effect of Gyu Hyosei Shingen instead of the effect of musk. A variety of prescriptions were prepared in accordance with the principles of Kampo medicine, with a focus on herbal medicines, and as a result of repeated studies on this, a new prescription with the addition of a spirit cat incense to the well-known beef yellow excluding musk was found to be a known beef containing musk. The present invention was found to have an effect equal to or greater than that of Seishin and completed the present invention. An object of the present invention is to provide a herbal medicine composition obtained by adding a spirit cat incense to a known formula of Gyu Hyosei Shingen excluding musk.

[0010]

SUMMARY OF THE INVENTION The present invention relates to a newly formulated beef yellow seishin, and more particularly, to the main constituent of a known beef yellow seishin excluding musk (musk), which is added to the main component of the known beef yellow spirit. And a method for producing the same. A new formulation of the present invention, Woowhangchungshimwo
n) The composition is a mountain medicine (San yak, Dioscorea rhizoma), licorice (Glycyrrhizae radix), ginseng (Ginseng radix), Gambah (Gourd, Typha)
e pollen), Koji (Shinkiku, Massa medicata ferment)
ata), soybean yellow roll (Glycine semengerminatum), cinnamon bark (Cinnamomi cortex), glue (Nicawa, Gelatinu)
m), Peony (Paeoniae radix), Bakumondo (Bakumondou, Liriopis tuber), Ogon (Scutel)
lariae radix), Toki (Touki, Angelicae gigantis r)
adix), windbreak (Leaf, Ledebouriellae radix), white ajutsu (Jyakujutsu, Atractylodis rhizoma alba), Saiko (Psycho, Bupleuri radix), bellflower (Kikyo, Plat)
ycodi radix), almond jelly (Kyounin, Armeniacae seme)
n), Bukuryo (Hoelen), Senkyu (Cnidi)
i rhizoma, Tragelaphus horn (Bezoar Bovi)
s), juniper (Antelopis cornu), ginger (kankyo, Borneolum), cow yellow (Gourd, Ampelopsis radi)
x), containing Zingiberis rhizoma, and further comprising Civet, along with the original composition of beef Huang Cheongsin without the muschus.

[0011] The composition of the present invention, from which musk has been removed from the musk, is preferably a herbal medicine of 13.0 to 17.0 w / w%, licorice.
9.0 ~ 12.0 w / w%, Ginseng 4.0 ~ 6.0 w / w%, Kamao 4.0 ~ 6.
0 w / w%, Koji rice 4.0-6.0 w / w%, Soybean yellow roll 3.0-5.0 w / w%,
Cinnamon bark 3.0-5.0 w / w%, glue 3.0-5.0 w / w%, peony 2.0-4.0 w
/ w%, Bakumon Winter 2.0-4.0 w / w%, Ougon 2.0-4.0 w / w%,
Toki 2.0-4.0 w / w%, Windproof 2.0-4.0 w / w%, Shiatsujutsu 2.0-4.0
w / w%, Saiko 2.0 ~ 4.0 w / w%, Bellflower 2.0 ~ 4.0 w / w%, Almond
2.0 ~ 4.0 w / w%, Bukuryo 2.0 ~ 4.0 w / w%, Senkyu 2.0 ~
4.0 w / w%, beef yellow 0.6-4.0 w / w%, Tragelaphus 1.0-3.0 w / w%,
It contains 1.0-3.0 w / w% dragon brain, 1.0-3.0 w / w% juniper, and 1.0-3.0 w / w% ginger. In the composition of the present invention, the incense cat incense is
It is contained at a ratio of 0.4 to 10.5 w / w%, preferably 0.8 to 6.9 w / w%, based on the weight of the whole crude drug excluding Reiko.

The spirit cat incense is a large spirit cat (Viverra Zibetha Linne,
It is obtained by scraping out secretions in the incense sac as secretions of spicy musk. The new product is a yellow-white liquid like honey, but when concentrated it turns into a brown ointment. The smell is good and the taste is bitter. A first-class product with a strong smell, white or light yellow color and no particles when placed on paper. Taste is spicy, warm and non-toxic in nature. The main pharmacological effects are effective on behavior, pain relief and labor. Another aspect of the present invention is a therapeutic agent for diseases of the circulatory system, central nervous system and autonomic nervous system, comprising the novel formulation of bovine yellow heart composition according to the present invention.

[0013]

BEST MODE FOR CARRYING OUT THE INVENTION The crude drug composition of the present invention can be administered in the form of pills, liquids and the like. The pills provided by the present invention are manufactured by a usual manufacturing method. That is, the pills of the present invention include a herbal medicine, licorice, ginseng, kabuki, koji, soybean yellow maki, cinnamon bark, glue, shakuyaku, barley winter, ougon, toki, windbreak, white jujube,
Precisely weigh Saiko, Kikyo, Almond, Bukuryo, Senkyu, Tragelaphus, Jerusalem, and Ginger, make fine powder with each herbal medicine, add finely ground beef yellow and dragon brain, mix and mix. , And after mixing the linging cat incense homogeneously, excipients such as honey are added to make a round, and a gold leaf garment is applied to produce a pill.

The present invention provides a method for producing a liquid preparation having the above-mentioned composition. That is, in the production method of the present invention, the spirit cat incense comprises a spirit cat tincture having a concentration of 5 w / v% in ethanol. Made and used, beef yellow and dragon brain each prepared as a fine powder, or included in β-cyclodextrin, used for herbal medicine, licorice, ginseng, kaoh, koji, soybean yellow maki, cinnamon, Jiao, Shakuyaku, Bakumondo, Ogon, Toki, Windbreak, Baijutsu,
Saiko, Kikyo, Almond, Bukuryo, Senkyu, Tragelaphus, Biallia, and Ginger can be prepared by using an extract obtained by reflux extraction or by mixing and using a suspension of these fine powders.

[0015] In detail, one of the methods is as follows: 1) The rest of the herbal medicine, licorice, ginseng, kabuki, koji, Soybean yellow roll, cinnamon bark, glue, peony, Bakumondo, Ougon, Toki, windbreak, white jujitsu,
Saiko, bellflower, apricot kernel, bukuryo, senkyu, Tragelaphus, juniper, and dried ginger are roughly or finely cut and purified water is added to produce a crude drug extract, or the fine powder of the crude drug material is 2% polyethylene glycol. Then, the mixture was stirred in a 1% propylene glycol water bath to produce a crude drug suspension, 2) a beta-cyclodextrin was encapsulated with beef yellow, and a betel yellow clathrate was produced.3) A beta-cyclodextrin was encapsulated with dragon brain. Manufacture a dragon brain clathrate in contact with it; 4) Manufacture a reticulum incense tincture (tinc) in which Reinko incense is dissolved in ethanol at a concentration of 5 w / v%; 5) Crude drug extract or crude drug suspension After adding a viscosity modifier to the solution and dissolving it with heat, mix it with beef clathrate clathrate, dragon brain clathrate and tincture tincture.6) Add honey or sucrose to this mixture and mix. Add propyl paraoxybenzoate and methyl paraoxybenzoate dissolved in ethanol After stirring, it can be produced by filling a container to adjust the pH adding citric acid and its salts.

Here, the crude drug extract in step 1) is precisely weighed to each of the above-mentioned drug materials and put into an extraction tank. After adding purified water, the mixture is reflux-extracted at 90-100 ° C., allowed to cool, and then filtered. To manufacture. Alternatively, the crude drug mixture of step 1) is a fine powder of each of the above-mentioned medicines, each of which is made into a fine powder and mixed by passing through a No. 200 sieve (Korean Pharmaceutical Co., Ltd.) or after mixing the above-mentioned medicines and then pulverizing them together. After passing through No. 200 sieve (Korean Pharmaceutical Co., Ltd.), the obtained powder is sufficiently mixed with 2,000 ml of a 2% aqueous solution of polyethylene glycol or 1% propylene glycol by stirring.

The beef yellow clathrate in step 2) is precisely weighed so that β-cyclodextrin (Cydex-P) is 0.5 to 0.9 w / v% of the total volume, and dissolved in purified water while heating. After leaving it to stand at room temperature, it is dried in a silica gel desiccator for 24 hours, then pulverized, passed through a No. 200 sieve, and then added to beef yellow which has been made into a fine powder, followed by stirring to produce.

The dragon brain clathrate in step 3) is prepared by dissolving β-cyclodextrin (Cydex-P) in purified water while heating it precisely to 0.2 to 1.3 w / v% based on the total volume. After leaving at room temperature, add ethanol to 0.7-1.3 w
/ v%, weighed precisely at room temperature, added to the above aqueous solution at room temperature, allowed to cool with stirring, and manufactured. Xanthane gum (Xanthane)
gum), polyvinylpyrrolidines, carboxymethylcellulose and its derivatives, and one or more selected from pectin, the amount of use is 0.1-0.4, 0.2-1.2, 0.1-0.5, respectively, based on the total volume. And 0.1-0.5 w / v
%.

Other methods are as follows: 1) A herb, licorice, ginseng, kabuki, god koji, soybean, which is obtained by cutting or excluding the remainder of the herbal medicine of the present invention except for the beef yellowtail, dragon brain, and ryoko. Manufactures a herbal extract extracted from perfused yellow roll, cinnamon bark, glue, peony, barley winter, ogre, toki, windbreak, white jujube, saiko, bellflower, apricot, bukuryo, senkyu, tragelapou, juniper, and ginger. 2) Polysorbates (Polysorbates) 0.3-2 w / v%, polyethylene glycols 0.3-2 w / v%, Cremopores 0.5-1.5
w / v%, sodium alginate 0.8-2.4 w / v%, one or more of these are selected and added, and reineko incense is added and suspended, and 3) mixing in step 2) Add fine powder of beef yellow and dragon brain to the solution and stir.4) Add the viscosity modifier, honey or sucrose to the mixed solution of step 3), mix and add sodium benzoate and propyl paraoxybenzoate and ethanol dissolved in ethanol. It can be produced by adding methyl benzoate, stirring, adding citric acid and a salt thereof, adjusting the pH, and filling a container.

The step 2) is carried out several times while adding and stirring a lingering scent with an ultrasonic device and stirring for 1 hour. Step 3) is carried out by drying with a silica gel desiccator for 24 hours, adding crushed and passed through a No. 200 sieve to form fine powdered beef yellow and dragon brain, applying an ultrasonic device with stirring, and stirring for 1 hour.

The acute oral toxicity of the composition of the present invention, which is prepared as described above, is evaluated for its acute oral toxicity, its safety is evaluated, its effects on the central nervous system, its effects on the autonomic nervous system, and its circulatory system. Experiments on the effect on
The pharmacological efficacy was compared with that of a known beef yellow heart preparation. As a result of comparing the efficacy of each of the prescription samples with each other, the prescription containing a spirit cat incense added to the prescription of the known beef yellow spirit excluding the musk showed the same or better effect than the known beef yellow seishin containing the musk .

[0022]

EXAMPLES Hereinafter, the present invention will be described in more detail with reference to Examples and Experimental Examples, but the present invention is not limited thereto. Examples 1 to 9: New formulation of Ushio Seishin's formula The formulations of Examples 1 to 9 are as shown in Table 1. The prescription in Table 1 corresponds to the dosage of 100 doses for adults. Comparative Examples 1 to 3 Comparative Example 1 is a prescription of a modified beef cow Huang Qing Xinyuan currently on the market,
Comparative Example 2 is a prescription of the original beef beef Huang Qing Xinyuan currently on the market,
Comparative Example 3 is a prescription of a half amount of beef yellow Kiyoshi Shingen currently on the market,
Each is shown in Table 1.

[0023]

[Table 1]

Example 10: Method for producing a new formulation of beef yellow Qing shingen pills 28.2 g of Yamayaku, licorice 20.0, excluding Reikoneko in the formulation of Example 2
g, Ginseng 9.7 g, Kamabou 10.0 g, Kojiro 10.0 g, Soybean yellow roll
7.0 g, cinnamon 7.0 g, glue 7.0 g, peony 6.0 g, wheat gate winter 6.0
g, Ougon 6.0 g, Toki 6.0 g, Windproof 6.0 g, White Juttsu 6.0
g, Saiko 5.0 g, Bellflower 5.0 g, Almond Jelly 5.0 g, Bukuryo 5.0 g, Senkyu 5.0 g, Tragelaphus horn 3.5 g, Jakren 3.0 g, Ginger
3.0 g, beef yellow 1.4 g, dragon brain 4.1 g were precisely weighed and mixed, then finely powdered, passed through No. 200 sieve (Korean medicine), and 1.5 g of Reikoneko incense was added and mixed homogeneously. , Honey and other excipients were added, and the mixture was rounded.

Example 11: Method for producing a new formulation of beef yellow spirit liquid preparation (1) Production of crude drug extract The remaining crude drug excluding beef yellow, dragon brain, and lyre incense in the formulation of Example 2 (28.2 g of mountain drug) , Licorice 20.0 g, ginseng 9.7 g, kaboshi 10
g, 10 g of koji, 7.0 g of soybean yellow maki, 7.0 g of cinnamon bark, 7.0 g of glue, 6.0 g of peony, 6.0 g of wheat gate winter, 6.0 g of ogong, 6.0 g of toki, 6.0 g of windproof, 6.0 g of white jitsugyu, Saiko 5.0 g, bellflower 5.0 g, apricot 5.0
g, Bukuryo 5.0 g, Senkyu 5.0 g, Tragelaphus 3.5 g, juniper 3.0 g, dried ginger 3.0 g), roughly cut and put into an extraction tank, add 1,300 ml of purified water, and then 4 at 100 ° C
The extract is refluxed for hours, allowed to cool, and passed through a No. 200 sieve to produce a crude drug extract.

(2) Production of beef clathrate clathrate 18 g of β-cyclodextrin (Cydex-P) is precisely weighed.
Dissolve in 300 ml of purified water while heating, leave at room temperature, dry in a silica gel desiccator for 24 hours, pulverize, pass through No. 200 sieve, add 1.4 g of beef yellow powder, and add enough for 2 hours To produce beef clath clathrate. (3) Manufacture of dragon brain clathrate Accurately weigh 20 g of β-cyclodextrin (Cydex-P)
Dissolve in 350 ml of purified water with heating, leave at room temperature, add 4.1 g of fine powdered dragon brain dissolved in 30 ml of ethanol, stir and cool to produce dragon brain clathrate I do.

(4) Production of tincture of Reiko cat Incense 1.5 g of Reiko cat incense is added to 27 ml of ethanol, heated and dissolved, cooled, and filtered. Add ethanol to the filtrate to make up to 30 ml. 1 ml of this spirit cat incense tincture is 50
It corresponds to ml. (5) Put the extract prepared in (1) in a mixing tank, add 6 g of xanthan gum, dissolve by heating and cool at room temperature.
After adding 00 g and mixing with stirring, the products prepared in (2), (3) and (4) are sequentially added, stirred and mixed well. (6) After dissolving 0.9 g of propyl paraoxybenzoate and 1.5 g of methyl parahydroxybenzoate in 80 ml of ethanol, add the mixture to the mixing tank of (5), gradually add 0.6 g of sodium benzoate and mix thoroughly. With acid and its salt
The pH is adjusted to 4.0, purified water is added to adjust the total volume to 3,000 ml, and the mixture is thoroughly stirred, homogenized, and filled into a 30 ml brown container.

Example 12: Method for producing a new formulation of beef yellow heart liquid The preparation method of Example 11 was repeated except that 8 g of pectin was used instead of 6 g of xanthan gum in (5). It is the same as the manufacturing method.

Example 13: Method for producing a new formulation of beef yellow heart liquid In the production method of Example 11, 18 g of β-cyclodextrin (Cydex-P) was used in the production of beef clathrate (2). 16.5 g of xanthan gum 10 in place of 20 g of β-cyclodextrin (Cydex-P) in the production of the dragon brain clathrate of (3), and 6 g of xanthan gum of (5). It is the same as the production method of Example 11 except that g is used.

Example 14: Production method of a new formulation of beef yolk heart liquid preparation In the production method of (2) beef yolk clathrate in the production method of Example 11, β-cyclodextrin (Cydex-P) was used instead of 18 g. twenty four
g, using 15 g of β-cyclodextrin (Cydex-P) instead of 20 g in the production of the dragon brain clathrate of (3),
It is the same as the production method of Example 11, except that 240 g of sucrose is used instead of 300 g of nectar in (5).

Example 15: Method for producing a new formulation of beef yellow heart liquid preparation In the production method of (3), in the production method of Example 11, β-cyclodextrin (Cydex-P) was used in place of 20 g. To 30
g of Example 5, except that 6 g of xanthan gum of (5) is replaced with 8 g of sodium carboxymethylcellulose and 270 g of sucrose is used instead of 300 g of nectar.
It is the same as the manufacturing method of No. 11.

Example 16: Method for producing a new formulation of Ganhuang Qingdao original liquid In producing the crude drug extract of (1) in the production method of Example 11, after adding 1,300 ml of purified water to an extraction tank, About 90
Instead of reflux extraction at 100100 ° C. for 4 hours, the remaining crude drugs except for beef yellow, dragon brain, and ryoko in the prescription of Example 2 were precisely weighed, finely powdered and made into a 2% aqueous solution of polyethylene glycol in 2%. It is the same as the production method of Example 11, except that the mixture is stirred to 1,300 ml to prepare a crude drug mixture.

Example 17: Method for producing a new formulation of Ganhuang Qingdao original liquid In the production method of Example 16, 1300 ml of a 1% aqueous propylene glycol solution was used instead of a 2% aqueous polyethylene glycol solution to stir the crude drug mixture. It is the same as the manufacturing method of Example 16 except that it is made.

Experimental Example 1: Stability test of a new formulation of beef yellow psychiatric composition I: Properties Using the sample prepared in Example 11, it was manufactured three times by the same operation, and the lot numbers were designated as LOT1, LOT2, and LOT1, respectively. Take 3 samples from each lot as LOT3 and set the sample number to S
AA, SA-B, and SA-C were tested. The storage conditions were room temperature storage (1-30 ° C, 40-55% RH: long-term storage test), and the storage and observation periods were immediately after production, 6 months, 12 months, 18 months.
Months, 24 months, 30 months, 36 months. (A) Test criteria: This drug is a brown opaque suspension with a unique fragrance. (B) Test results: shown in Table 2 below.

[0035]

[Table 2]

EXPERIMENTAL EXAMPLE 2: Stability test of a freshly formulated beef yellow spirit composition II: pH test The specimen, storage conditions, storage and observation period were the same as in Experimental example 1. (B) Test criteria: pH 3.0 to 5.0 (b) Test method: The composition of Example 11 was tested according to the pH test method in the Korean Korean Pharmaceutical General Test Method. (C) Test results: shown in Table 3 below.

[0037]

[Table 3]

Experimental Example 3: Stability test of a new formulation of beef yellow heart composition III: Specific gravity The specimen, storage conditions, storage and observation period were the same as in Experimental Example 1. (B) Test criteria: 1.004 to 1.104 (b) Test method: The composition of Example 11 was used in the Korean general test method.
The test was performed according to the third method of the specific gravity test method. (C) Test results: The results are shown in Table 4 below.

[0039]

[Table 4]

Experimental Example 4: Stability test of freshly formulated beef yellow heart composition IV: Evaporation residue test Samples, storage conditions, storage and observation period were the same as in Experimental Example 1. (A) Test standard: 20.4 to 27.6 w / v% (B) Test method: Accurately take 10 ml of the composition of Example 11, dry at 105 ° C for 4 hours in advance, and cool in a desiccator (silica gel). Thereafter, the mixture is placed in a weighed beaker, concentrated by evaporation on a water bath, dried at 105 ° C. for 4 hours, cooled with a desiccator (silica gel), weighed precisely, and the weight difference before and after is determined. The difference in weight before and after the measured volume is defined as evaporation residue. (C) Test results: shown in Table 5 below.

[0041]

[Table 5]

Experimental Example 5: Stability test of freshly formulated beef yellow heart composition V: Content of bound bilirubin in beef yellow Sample, storage conditions, storage and observation period were the same as in Experimental Example 1. (B) Test criteria: Labeled amount (Bound bilirubin 1.68 mg / 30 m
(b) Test method: Accurately take 30 ml of the composition of Example 11 (corresponding to 1.68 mg of conjugated bilirubin), place it in a 300 ml round bottom flask, add 10 ml of dilute hydrochloric acid and chloroform. After adding 50 ml and attaching a reflux condenser, the mixture is heated on a water bath for 40 minutes, transferred to a separating funnel, and the chloroform layer is dehydrated with anhydrous sodium sulfate and filtered. The aqueous layer is again extracted with chloroform three times in 50 ml portions, and the chloroform layers are combined and further added with chloroform to make a exactly 200 ml solution to be a total bilirubin test solution.

Separately, 30 ml of the test drug (conjugated bilirubin 1.6
(8 mg equivalent), take exactly 100 ml into a separatory funnel, add 30 ml of chloroform, stir for 10 minutes, dehydrate the chloroform layer with anhydrous sodium sulfate and filter. The aqueous layer is again extracted twice with 50 ml of chloroform, and the chloroform layers are combined. Further, chloroform is added, and the solution accurately adjusted to 200 ml is used as a free bilirubin test solution. Separately, accurately weigh approximately 2.0 mg of a bilirubin standard product and dissolve it in chloroform to make 200 ml. The above test solution and standard solution are tested by the liquid chromatography method under the following experimental conditions.

Operating conditions Column: Shim-pak CLC-ODS Detector: UV absorption spectrophotometer (measuring wavelength 436 nm) Mobile phase: methanol: 2% glacial acetic acid (90:10) Flow rate: 1.2 ml / min

[0045]

(Equation 1)

(C) Test results: The results are shown in Table 6 below. The test was performed three times for each lot, and the average value was described.

[0047]

[Table 6]

Experimental Example 6: Stability test of freshly formulated beef yellow heart composition VI: Content of glycyrrhizic acid in licorice Samples, storage conditions, storage and observation period were the same as in Experimental Example 1. (B) Test criteria: Labeled amount (glycyrrhizic acid 4.04 mg / 30 m
(b) Test method: Accurately take 60 ml (equivalent to 8.08 mg of glycyrrhizic acid) of the composition of Example 11, attach a reflux condenser, and add 50 ml of 3 M sulfuric acid. Hydrolyze for 1 hour on a water bath. After cooling, 50 ml of chloroform was added, and the mixture was refluxed and heated on a water bath for 30 minutes. After cooling, transfer to a separatory funnel and remove the chloroform layer.
The chloroform layer is combined by repeating extraction three times in ml, and filtered through anhydrous sodium sulfate. After concentrating the remaining solution under reduced pressure, dissolve the residue in methanol
l. Separately, weigh about 8.08 mg of glycyrrhizic acid for quantification, and use the solution prepared by the same method as the test solution below as the standard solution. Test solution and with a standard solution 10μl measuring the glycyrrhizic acid peak area A _T and A _S of Kakueki tested by liquid chromatography under the following conditions.

Operating conditions Detector: UV absorption spectrophotometer (measuring wavelength 254 nm) Column: Stainless steel tube of 4-6 mm in inner diameter and 15-20 cm in length
Pack 5-10 μm octadecylsilylated silica gel. Mobile phase: methanol / water / glacial acetic acid (78: 19: 3) Flow rate: 1.0 ml / min

[0050]

(Equation 2)

(C) Test results: The results are shown in Table 7 below. The test was performed three times for each lot, and the average value was described.

[0052]

[Table 7]

Experimental Example 7: Stability test of a new formulation of beef yellowish heart component VII: Total borneol content (%) in dragon brain Sample, storage conditions, storage and observation period were the same as in Experimental Example 1. Met. (B) Test criteria: Labeled amount (total borneol 38.58 mg / 30 ml)
(B) Test method: accurately take 30 ml of the composition of Example 11
The mixture was put into a 1 ml separating funnel, 50 ml of chloroform was added, and the mixture was shake-extracted. The chloroform layer was dehydrated and filtered with anhydrous sodium sulfate. The aqueous layer is again extracted three times with 50 ml of chloroform each time, and the combined chloroform is added. Separately, accurately weigh 14.2 mg of the iso-borneol standard and 22.8 mg of the nor-borneol standard and dissolve in chloroform to make exactly 200 ml to make a standard solution. The above test solution and standard solution are tested according to the gas chromatography method under the following operating conditions.

Operating conditions Column: 10% PEG-20M Chromosorb (WAW-DMCS) 60-80 m
esh Column temperature: 140 to 180 ° C (5 ° C per minute) Injection section temperature: 230 ° C Detection section temperature: 230 ° C Detector: Flame ionization detector Moving gas: Nitrogen gas Flow rate: 40 ml / min

[0055]

(Equation 3)

(C) Test results: The results are shown in Table 8 below. The test was performed three times for each lot, and the average value was described.

[0057]

[Table 8]

Experimental Example 8: Stability test of a new formulation of beef yellow spirit composition VIII: Civetone content (%) in spirit cat incense Samples, storage conditions, storage and observation period were the same as in Experimental Example 1. Met. (B) Test criteria: For the indicated amount (cibetone 0.3 mg / 30 ml)
90.0% or more (b) Test method: 450 ml of the composition of Example 11 (4.5 mg of cibetone)
Accurately), put it into a separatory funnel, and add chloroform 600
After extracting with shaking three times in ml, the chloroform layers are combined, dehydrated and filtered with anhydrous sodium sulfate, concentrated under reduced pressure, and dissolved in 50 ml of chloroform to prepare a test solution. Separately, about 20 mg of cibetone standard (firmenich) is precisely weighed and dissolved in chloroform to make exactly 100 ml to make a standard solution.
The above-mentioned test solution and standard solution are tested according to the gas chromatography method under the following operating conditions.

Operating conditions Column: 10% OV-17 Chromosorb WHP 100/120 stainless steel packed column (6 ft, 2 mm) Detector: Flame ionization detector Injection section temperature: 230 ° C Detection section temperature: 240 ° C Column temperature : 210-224 ° C Initial time: 20 minutes Temperature rise rate: 0.5 ° C / min Final time: 2 minutes Moving gas: Nitrogen flow rate -60 psi Air flow rate -40 psi Hydrogen flow rate -30 psi

[0060]

(Equation 4)

(C) Test results: The results are shown in Table 9 below. The test was performed three times for each lot, and the average value was provided.

[0062]

[Table 9]

The properties, pH test, specific gravity test, evaporative residue test, conjugated bilirubin content test, glycyrrhizic acid content test in licorice, total borneol content test, and As a result of the test for the content of civetone in the incense, all the test items met the criteria of each item under room temperature storage conditions from immediately after production to 36 months after production, and the stability of the beef yellow Qingxin original composition of the new formulation of the present invention Was confirmed.

Experimental Example 9: Acute toxicity test of a new formulation of beef yellow heart composition Test method The test was carried out in accordance with the Notification of the Food and Drug Safety Headquarters, No. 1996-8 (96.4.16), "Standards for Toxicity of Pharmaceuticals, etc." (1) Experimental animals Seven-week old female and male Sprague-Dawley SPF rats produced in a clean area were purchased and purchased in a laboratory (temperature 24 ± 2 ° C, humidity 55 ± 5%). Acclimation for 2 weeks (accl
During the acclimatization period, general symptoms were observed, and only normal animals were selected and used for the test. During the test period,
Solid feed and water were sufficiently supplied and used.

(2) Experimental specimen Example 2 The crude drug excluding beef yellow, dragon brain, and erythema incense in the formulation of Table 1 was roughly cut, and a 10-fold amount of purified water was added thereto. Ten
The solution was refluxed at 0 ° C for 4 hours, allowed to cool, and allowed to pass through a No. 200 sieve. After freeze-drying, the powder was made into a fine powder and passed through a No. 200 sieve to produce powder. The powder obtained by converting each of the cat incense into a fine powder was passed through a No. 200 sieve and dispersed and mixed to prepare a mixed powder. This was diluted and suspended in carboxymethyl cellulose before use according to the experimental administration dose, and used as an experimental sample.

(3) Administered dose The maximum administrable dose of 2,100 mg / kg administration group, which is the maximum administrable dose of the new formulation of bovine yellow heart composition, was set as the highest dose group, and the 26 mg / kg administration group was set as the lowest dose group. Dose groups (2,100, 70
0, 233, 78, 26 mg / kg) and a control group were set, and the preparation was prepared at the time of use and orally administered once.

(4) Observation Items (a) Observation of Clinical Symptoms and Number of Dead Animals Observation of clinical symptoms and the number of dead animals for all experimental animals were performed every hour for 6 hours immediately after drug administration, and 11 days from the day after administration. The animals were observed once daily for changes in general condition, toxic symptoms and death. (B) Weight measurement The body weight of all experimental animals used in the test was measured immediately before administration of the experimental sample, and on days 1, 3, 6, 9, 12, and 14 after administration. (C) Necropsy After completion of the test, the animals were weighed, anesthetized with ether, and the sublingual artery and abdominal aorta were cut off and killed. Then, the appearance and internal organs were observed with naked eyes in detail. All tissues in which suspicious abnormal findings were observed were fixed in a 10% formalin solution to observe the findings with a microscope.

2. Test results No oral fatalities or abnormal symptoms were observed in any of the female and male dose groups when the test substance was orally administered. During the experimental period, there was no significant change in body weight in the administration groups of all females and males compared to the control group, and no abnormal findings were visually observed at the time of dissection after completion of the experiment. Based on the above results, the LD ₅₀ value of the new formulation of Gyu-Huang Seishin original composition was 2,100 mg / kg, which is the maximum dose that can be administered to rats used in this experiment (about 3% of the clinical dose).
10 times) or higher, and measurement at higher doses was not possible and was evaluated as a safe drug.

[0069]

[Table 10]

Experimental Example 10: Efficacy test of a new formulation of Ganhuang Qingyin original composition I: Effect on cerebral ischemia Experimental animals After acclimatizing Mongolian-Gerbil rats (body weight 60-100 g) for about one week, select healthy animals and choose a temperature of 23 ± 3.
° C, relative humidity 50 ± 10%, exhaust 10-12 times, fluorescent light 12
The animals were bred in an environment with an hr cycle of 150-160 lux. During the experiment, water and feed were freely supplied and adapted to the laboratory. After that, only normal animals showing no abnormality in general symptoms were selected and used for the experiment.

2. Experimental sample The experimental sample manufactured with the formulation of Example 2 in Table 1 was AT (containing Rei Neko Ka) and the experimental sample manufactured with the formulation of Example 5 was AF (containing Rei Neko Ka). The experimental sample thus produced was BT (containing musk), and the experimental sample prepared by the formulation of Comparative Example 2 was BF (containing musk). The preparation was suspended using sodium carboxymethylcellulose to prepare an experimental sample.

3. Experimental method (1) Induction of ischemia Mongolian Gerbil
(Body weight 60-100 g) was used to induce cerebral ischemia by carotid artery ligation. Experimental animals were anesthetized with 3% isoflurane and the concentration was reduced to 1% or 2% after the animals were anesthetized, and anesthesia was maintained during the entire operation. After incising the skin at the neck and separating the muscle, the carotid artery was separated from the vagus nerve and surrounding tissues, and the carotid arteries on both sides were closed for 10 minutes using forceps for ligating the carotid artery. To confirm the effect of closing the carotid artery on blood supply to the cerebral tract, after occlusion of the carotid artery, ophthalmoscopes were used to confirm whether the thickness of the ophthalmic artery in a portion of the middle cerebral artery was reduced. Using a rectal probe to measure body temperature throughout the course of inducing cerebral ischemia,
Body temperature was maintained above 37 ° C. using a heating pad connected to a rectal probe. In the sham control group, the carotid artery was isolated but not closed after anesthesia in the same manner. After surgery, they were isolated after waking up from anesthesia and had free access to food and water.

(2) Treatment of experimental animals As shown in the figure below, 150 μl of the drug was
Oral administration was performed twice at 12-hour intervals. The same amount of distilled water was administered to the control group instead of the drug, and the body weights of the control group and the administration group were measured before administration in the morning. On the 7th day after starting administration,
Surgery was performed to induce cerebral ischemia about 3 to 4 hours after finishing the morning dosing, and the animals after the surgery resumed drug administration after about 12 hours. After 5 days from the operation, the administration was completed in the morning. About 3 to 4 hours later, the mice were sacrificed, and a fixative was injected through the heart to fix the brain.

[0074]

(Equation 5)

(3) Treatment of Tissue The experimental animal 5 days after the induction of ischemia was replaced with isoflurane (5
%), The thoracic cavity was opened, and a fixative was perfused through the aorta to fix the brain. Before injecting the fixative, inject 50 ml of a calcium-depleted tyroid solution to completely remove blood from the tissue, and then add a 0.4 M phosphate buffer solution containing 4% paraformaldehyde and 0.2% picric acid (Lan
a's fixative) was perfused to fix the brain. The fixed tissue was treated with the same fixative for 4 hours, and then fixed.
The cells were sequentially precipitated in a TPBS solution containing 0% sucrose and treated so as not to damage the tissue during freezing. Tissues after sucrose treatment are quickly frozen on dry ice at -65 ° C or lower using a tissue freezing machine, and then Bregma with a cryosectioner-
Tissues from 2.34 mm to Bregma -3.14 mm were cut into 10 sections of 40 μm thickness at 80 μm intervals.

(4) Immunohistochemical assay for MAP2 The prepared tissue was prepared by adding TPBS (Tris Phosphate) supplemented with 3% hydrogen peroxide to reduce the activity of endogenous peroxidase.
Buffered Saline) for 30 minutes, then add 1% normal rabbit serum and 0.3% Triton-X in TPBS.
Time processed. MAP2 (microtubul
The reaction was carried out at 4 ° C. for 12 hours using e associated protein 2) antiserum (Sigma, 1: 80000). Tissues that have completed the reaction with the primary antibody are rabbit anti-mouse IgG (vector,
1: 200) for 1 hour at room temperature, followed by reaction with an avidin-biotin complex (Elite Kit, Vector, 1: 250) for 30 minutes at room temperature. The treated tissue is reacted again with biotinylated tyramine (BT: 1 μl BT / ml PBS + 0.005% H ₂ O ₂ ) for 20 minutes at room temperature, and then avidin-biotin complex (1:
The reaction was induced for 1 hour at room temperature using the method of (250). After completion of each step, the residual antibody is removed six times for 5 minutes each using TPBS, and then proceed to the next step, where the avidin-biotin complex
After the reaction with (ABC) is completed, DAB (deaminobenzidin
e) The reaction was developed at room temperature. The tissue after color development was completely dried on a slide glass, dehydrated while increasing the concentration of alcohol, and then treated with xylene and covered with a cover glass.

(5) Tissue Observation and Statistical Processing The hippocampus portion was injured at 50 × magnification from ischemia from ten immunostained tissues using an image analyzer (Metamorph, unversal imaging Co.). The area was measured. Compared to the sham control group, the area where staining is significantly reduced is regarded as the area damaged by ischemia (ischemic area), and the area showing MAP2 staining in this area (stained nerve) The total area of the fiber regions was measured together, and the ratio was calculated. Average staining density of nerve fibers observed in sham control group
For (mean density of stained fiber), the average area observed in the administration group in which ischemia was induced was measured, and then the ratio of the area of the nerve fiber showing the staining property in the average area was calculated. The ratio of the area where MAP2 staining is recognized to the area damaged by ischemia observed from the ischemia-induced group compared to the average staining density of the sham control group was calculated as a percentage of the average staining density of the sham control group. , T-Test was used to verify the significance. The ratio of the average staining density of the administration group to the average staining density of the control group was calculated using the following formula.

[0078]

(Equation 6)

To determine the change in body weight of the experimental animals that occurred during the administration period, the body weight before surgery on day 7 and the body weight on day 12 were calculated as a percentage of the body weight on the day on which administration was started. The difference between the control group and the administration group was analyzed by t-Test. 4. Experimental results (1) Changes in body weight Changes in body weight appearing around day 7 (day of induction of ischemia) after starting administration showed no significant difference in each experimental group, and were observed around day 5 after induction of ischemia. The body weight of the control group and the BT administration group showed a sharp decrease compared to the initial body weight and the body weight measured around day 7 (Table 11). However, in the BF, AT and AF administration groups, no significant decrease was observed as compared with the initial body weight and the body weight observed around day 7. The body weight of the control group and the BT administration group observed around day 12 showed a significant decrease compared to the body weight observed in the other administration groups. From these results, it was observed that the BF, AT, and AF administration groups effectively suppressed weight loss caused by ischemia induction, while the BT administration group could not inhibit weight loss due to ischemia.

[0080]

[Table 11]

(2) Measurement of area damaged by ischemia Table 12 shows the mean area and MA of the area where ischemia occurred as a result of immunostaining in the hippocampus of Gerbils rats following induction of ischemia.
The average area of the area stained by P2 immunohistochemistry and the ratio of the area of the stained area to the area of the ischemic area were expressed. MA observed in sham control group and ischemia-induced control group
The P2 immune dyeability was observed in the fiber pattern. MAP2 due to ischemia
The change in the staining property was remarkable mainly in the CA1 and CA2 portions of the hippocampus, and the number of nerve fibers showing resistance to ischemia was increased in the drug-administered group compared to the control group. Comparing the entire injured area where MAP2 immunostaining decreased due to ischemia observed in the drug-administered group, no significant difference was observed compared to the control group. Thus, it was observed that the total area of the ischemic injury due to drug treatment was not affected.

[0082]

[Table 12]

(3) M in the area damaged by ischemia
Changes in AP2 stainability The total area of MAP2 stainable nerve fibers observed in the area damaged by ischemia showed a significant increase in the BF, AT and AF treatment groups compared to the control group In the BT administration group, no difference was shown as compared with the control group. On the other hand, the average staining density observed in the sham control group was measured as 86.32%, and the ratio of the staining density observed in the control group and the drug administration group to this average staining density was calculated. However, there was no significant difference in the BT administration group from the control group. When comparing drug administration groups, MA between each group in the area affected by ischemia
The ratio of P2 staining was significantly different between the BF-administered group and the BT-administered group, but no significant difference was observed between the AF and AT-administered groups.

Experimental Example 11: Efficacy test of a new formulation of beef yellow heart composition II: Effect on hypertension Experimental animal Same as Experimental example 10 except that SHR white rats (weight: 180-220 g) were used instead of Mongolian-Gervirus rats. 2. Experimental specimen Same as Experimental example 10.

3. Experimental method One group of SHR white rats consisted of 7 animals, each group weighing 270-28 on average.
It was adjusted to be about 0 g. The oral dose of the test drug is 0.85 ml / 200 g for AF and BF, and 0.5 ml / 200 g for AT and BT.
And administered twice daily after measuring the arterial blood pressure. Micro arterial blood pressure measurement is a multi-channel blood pressure monitor
Pulse rate was measured together with blood pressure measurement using 8000 (TSE, Technical and Scientific Equipment). Experimental control SH
R white rats were kept in a 37 ° C incubator for 15 minutes before blood pressure measurement to maintain a constant body temperature.

[0086] 4. Experimental results The test drug was orally administered twice daily to 7 SHR white rats per group, and the microarterial blood pressure was measured.As a result, all the experimental groups except the experimental group to which the experimental sample BT was administered were compared to the control group. Blood pressure was observed to decrease (Table 13). In particular, AT and BF
In the case of the administration group, a continuous decrease in blood pressure was observed during the administration period, and the blood pressure of all experimental groups was statistically significantly lower than that of the control group (P <0.05, P <0.01). The pulse rate through the microarteries was recorded together with the measurement of blood pressure, but no change in pulse rate was observed between the control group and the experimental group (Table 14).

[0087]

[Table 13]

[0088]

[Table 14]

Experimental Example 12: Efficacy test of a new formulation of beef yellow spirit composition III: Effect on enhancement of heart irritation Experimental animal Same as Experimental example 10 except that a rabbit (body weight 2.5 to 3.0 kg) was used instead of the Mongolian-Gervirus rat. 2. Experimental specimen Same as Experimental example 10.

3. Experimental method Rabbits in the experimental group, after 30 days of long-term administration, were anesthetized and fixed on their backs.Then, the incision was made from the lower part of the thorax to the head, the exposed diaphragm was incised, and the thorax was lifted up to the head. After fixation, tissues such as fat were separated from the heart to expose the aorta. A silk thread was allowed to pass under the exposed aorta, and after traversing the aorta, a tube was inserted so that the perfusate flowed to the coronary artery, and was fixed with the silk thread that had been passed before. After removal of the immobilized heart, it was connected to a previously prepared Langedorf apparatus, taking care not to allow air to enter. The chamber at the top of the device should be well supplemented with Krebs solution and a perfusion pressure of 60 mm with a 95%: 5% mixture of oxygen and carbon dioxide.
Hg and pO ₂ were adjusted to 580 mmHg or more. A force transducer (M) is attached to the left ventricular end of the connected heart.
After connecting yoGraph F60 (Narco biosystem) and stabilizing for about 30 minutes, the heart rate and myocardial contractility were measured using Physiograph MKIII (Narco biosystems). 10 μm each of 20 μM epinephrine and 20 μM acetylcholine chloride included in the conditions for inducing heart disease during the measurement period of heart rate and myocardial contractility
By flowing each l together with the perfusate, changes in heart rate and myocardial contractility of each experimental group and control group were observed. In general, the heart rate is expressed in beats per minute, but in this experiment, the overall reaction time to epinephrine and acetylcholine chloride is within 1 to 2 minutes, so it is expressed as the number of beats per 10 seconds did.

4. Experimental results After extraction of the hearts of the experimental and control groups to which each test drug was administered for a long period, the myocardial contractility after stabilization by connecting to a perfusion device was
The AF administration group was larger than the control group (Table 15). The isolated heart was treated with epinephrine and acetylcholine to cause arrhythmia, ischemic effect, and the like, and the results were recorded as myocardial motility calculated from muscle contractility and pulse rate (Table 16). When infused with epinephrine, which induces myocardial excitation, the control group had approximately 41
An 8% increase was observed (Table 17, FIG. 1). Thus, epileprine treatment of the isolated heart dramatically increased myocardial motility in the control group, but significantly decreased myocardial motility in the experimental group that had long-term administration of the BF formulation compared to the control group. (P <0.05, P <0.01).

[0092]

[Table 15]

[0093]

[Table 16]

[0094]

[Table 17]

When treated with acetylcholine, the control group had about 17% myocardial motility, indicating lower myocardial function than the test drug-administered group (Table 18, FIG. 2). Unlike the control group, the acetylcholine treatment reduced the rate of decrease in myocardial motility in the experimental group to which AF and BT were administered for a long time (P <0.05, P <0.01).

[0096]

[Table 18]

Table 19 shows a sudden change in muscle contraction force for 60 seconds before and after administration of epinephrine and acetylcholine.
The change in contractile force during epinephrine treatment was smaller in the long-term administration group of the BF formulation than in the control group, and the change in contractile force during treatment with acetylcholine was smaller in the long-term administration group of AF and BF formulation than the control group (P <0.05, P <0.01).

[0098]

[Table 19]

Experimental Example 13: Efficacy test of a new formulation of bovine yellowish heart composition IV: Effect on central nervous system and autonomic nervous system Experimental animal Same as Experimental example 10 except that an ICR mouse (body weight 20-30 g, male) was used in place of the Mongolian-Gervirus rat. 2. Experimental specimen Same as Experimental example 10.

3. Experimental method (1) Effect on hexobarbital-induced sleep time Test drug (AT, AF, BT, B)
F) and a control drug (chlorpromazine 4 mg / kg) were orally administered, and after 30 minutes, 50 mg / hexobarbital sodium was added.
The sleep time induced by intraperitoneal injection of kg, ie the time from loss of postural reflex to recovery, was measured. (2) Effect on strychnine-induced lethality ICR mice were treated as a group with 10 test drugs (AT, AF, BT,
BF) and control drug (phenobarbital sodium 10
0 mg / kg) was orally administered and 30 minutes later, 1.5 mg / kg of strychnine nitrate was injected subcutaneously, and the time from the onset of induction of rigid convulsions to death was recorded.

(2) Effect on Spontaneous Motor A test was conducted using a spontaneous motor measurement apparatus (activity cage: Ugo Basile), and eight ICR mice were used in one group.
Adapt the mouse to the locomotor activity measuring device for 30 minutes
(AT, AF, BT, BF) and a control drug (chlorpromazine hydrochloride 4 mg / kg) were orally administered, and after 1 hour, spontaneous motility was measured for 15 minutes.

Experimental Results (1) Effect on Hexobarbital-Induced Sleep Time Table 20 shows the results of measuring the sleep time induced by hexobarbital. The sleep time (2089.2 seconds) of the chlorpromazine hydrochloride group used in the positive control group was longer than the sleep time (992.5 seconds) of the control group, and BF with a musk formulation and AT and AF with a prescription containing a spirit cat were administered. The duration of sleep in the tested group was 41% and 34%, respectively, compared to the duration of sleep in the positive control group.
%, An increase rate of 66%.

[0103]

[Table 20]

(2) Effect on strychnine-induced lethality Table 21 shows the results of the strychnine-induced convulsive lethality test. AT administration group in the containing formulation was 290.7 seconds, 321.7 seconds, 305.6 seconds respectively,
This shows that the delay was significantly delayed as compared with the control group (234.8 seconds).

[0105]

[Table 21]

(3) Effect on spontaneous motility Table 22 shows the change in spontaneous motility after administration of the test drug. In the control group, 1369.3 of spontaneous motility was observed. Spontaneous motor ability decreased in the drug administration group.

[0107]

[Table 22]

Experimental Example 14: Efficacy test of a new formulation of beef yellow spirit original composition V: Effect on stress Experimental animal Same as Experimental example 10 except that SHR white rats (weight: 180-220 g) were used instead of Mongolian-Gervirus rats. 2. Experimental specimen Same as Experimental example 10.

3. Experimental method Test rats (AT, AF, BT, BF) were orally administered to rats that had been fasted for 24 hours in groups of 10 SHR rats, and after 2 hours had passed, they were restrained in a metal tube restrainer and then water bathed. Soda (20 ± 2 ℃)
For 24 hours. The white rats subjected to the stress loading were anesthetized with ether, and the abdomen was incised to remove the gastrointestinal tract and adrenal glands. The removed organs are weighed after the fat tissue or capsule has been completely removed, and the adrenal glands are
Homodunate with 5% trichloroacetic acid (TCA) solution was used to measure ascorbic acid content in adrenal gland and protein content in adrenal gland. That is, after the homogenized solution was centrifuged (13,000 rpm, 10 minutes), 0.5 ml of the supernatant and 0.5 ml of the TCA solution, 0.8 ml of dipyridyl, 0.1 ml of phosphoric acid, and 0.1 ml of ferric chloride were added. The absorbance was measured at nm. The protein content in the adrenal gland was assayed according to the method of Bradford using bovine serum albumin as a standard solution.

4. Experimental Results Table 23 shows the effect of the test drug on rats that had been subjected to a 24-hour water immersion stress load. The adrenal gland was not enlarged by stress, but the ascorbic acid content in the adrenal gland was reduced by about 52% in the control group compared to the normal group without stress. On the other hand, the BF administration group with the prescription containing musk decreased by about 17%, and the AT administration group with the prescription containing Rei Nekoko decreased by about 32% .Ascorbic acid in the adrenal gland due to stress was reduced by each test drug. It was significantly suppressed. In the case of the gastrointestinal tract, the weight of the gastrointestinal tract in the control group was reduced by 45% compared to the normal group without any stress.
The reduction in the weight of the gastrointestinal tract due to stress was suppressed at a reduction rate of 29%.

[0111]

[Table 23]

[0112]

According to the present invention, the novel formulation of Guangyin Qingxin original composition contains musk for circulatory system, central nervous system and autonomic nervous system symptoms, such as blood pressure, for which Guangyin Qingyuan has been used. Efficacy is equal to or better than the original beef yellow Qingyuan.

[Brief description of the drawings]

BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a diagram showing the effect of a bovine yellowish heart composition of a new formulation of the present invention on the myocardial contractility of the isolated heart of epinephrine-treated rabbits.

FIG. 2 is a diagram showing the effect of the bovine yellowish heart composition of the new formulation of the present invention on the myocardial contractility of the isolated heart of rabbits treated with acetylcholine.

Continuation of the front page (51) Int.Cl. ⁶ Identification code FI A61K 35/32 A61K 35/32 35/84 35/84 A (72) Inventor Yohorn Aan Korea, Seoul, Kwanjink, Kwanjandon 554-7, Hyundai・ Apart 506-702

Claims (6)

[Claims] [Claim 1] Yamayaku, licorice, ginseng, ginseng, koji, soybean yellow maki, cinnamon bark, glue, peony, barley winter, ougon, toki, windbreak, white jujube, saiku, bellflower, apricot kernel, bukuryo A new formulation of a beef yellow spirit original composition comprising a scent, a tragelaphus horn, a sycamore, a ginger, a beef yellowtail and a dragon brain, and a muscule-free beef yellowish heart original composition and a lyre cat incense. 2. A method for preparing a beef yellow spirit composition from which musk has been removed.
13.0 ~ 17.0 w / w%, Licorice 9.0 ~ 12.0 w / w%, Ginseng 4.0 ~
6.0 w / w%, kabuki 4.0-6.0 w / w%, Kamijikoji 4.0-6.0 w / w%, soybean yellow roll 3.0-5.0 w / w%, cinnamon bark 3.0-5.0 w / w%, glue 3.0-5.0
w / w%, Peony 2.0-4.0 w / w%, Bakumondo 2.0-4.0 w / w%, Ougon 2.0-4.0 w / w%, Toki 2.0-4.0 w / w%, Windproof 2.0-
4.0 w / w%, Jakuju 2.0-4.0 w / w%, Saiko 2.0-4.0 w / w%, Bellflower 2.0-4.0 w / w%, Almond Jin 2.0-4.0 w / w%, Bukuryo 2.0-4.0 w /
w%, Senkyu 2.0-4.0 w / w%, beef yellow 0.6-4.0 w / w%, Tragelaphus 1.0-3.0 w / w%, Dragon brain 1.0-3.0 w / w%, juniper 1.
2. The new formulation of beef yellow spirit composition according to claim 1, comprising 0-3.0 w / w% and 1.0-3.0 w / w% ginger. 3. The original composition of beef yellow cherries of the new formulation according to claim 1 or 2, wherein the composition ratio of the witch cat is 0.4 to 10.5 weight ratio (w / w) to the whole crude drug weight excluding the witch cat. Stuff. 4. A therapeutic agent for diseases of the circulatory system, central nervous system and autonomic nervous system, comprising the novel composition of bovine yellowish heart according to claim 1. 5) 1) Yamayaku, licorice, ginseng, kabuki, koji,
Soybean yellow roll, cinnamon bark, glue, peony, Bakumondo, Ougon, Toki,
Precisely measure and finely mix windbreak, white jujube, saiko, bellflower, apricot kernel, bukuryo, senkyu, tragelapou horn, sycamore and dried ginger, and then mix finely ground beef yellow and dragon brain to produce a mixed powder. 2) A method for producing a pill of a new formulation of Gyu-Huang Qing Xin Yuan composition, which is prepared by mixing honey cat incense homogeneously, adding honey and rounding and applying gold leaf garment. 6) 1) Yamayaku, licorice, ginseng, kabuki, koji,
Soybean yellow roll, cinnamon bark, glue, peony, Bakumondo, Ougon, Toki,
Windproof, white jujube, saiko, bellflower, almond, bukuryo, senkyu, tragelapou horn, juniper and dried ginger are roughly cut or minced, and purified water is added and refluxed to produce a crude drug extract, 2) β-cyclo Manufacture of beef yellow clathrate in which dextrin is included in beef yellow, 3) manufacture of dragon brain clathrate in which beta-cyclodextrin is included in dragon brain, 4) 5 w / v% 5) Reconciled tincture tincture dissolved in ethanol at a concentration of 5) .5) After adding a viscosity modifier to the crude drug extract and dissolving by heating, mix with beef yellow clathrate, dragon brain clathrate and Reinko tincture. 6) Add nectar or sucrose to this mixed solution, mix, add sodium benzoate, propyl paraoxybenzoate and methyl paraoxybenzoate dissolved in ethanol, stir, add citric acid and its salt, and add pH. Of a new formulation of Ganhuang Qingyuan original composition, characterized by adjusting and filling Manufacturing method.