JPS615024A - Preparation of crude drug pharmaceutical - Google Patents

Abstract

PURPOSE:To obtain a low toxic and nonhygroscopic crude drug pharmaceutical, by extracting a crude drug containing astractyloide rhizoma or/and magnolia bark or a mixture thereof with water or water containing cyclodextrin, vacuum concentrating the resultant extract, and spray-drying the concentrated extract. CONSTITUTION:A crude drug containing astractyloides rhizoma or/and magnolia bark or a mixture thereof (which may further contain one or plural crude drugs of citrus unshiu peel, licorice, wild siamese cardamom, cyperi rhizoma, dried ginger, etc. is extracted with water or water containing cyclo dextrin (various materials obtained by hydrolyzing starch with an acid or amylase). The amount of the cyclodextrin to be used is 0.01-0.1 of that of the raw material crude drug or mixture thereof. The resultant extract is then concentrated under reduced pressure to give a concentrate, which is then spray-dried in the presence of the cyclodextrin to afford the aimed crude drug pharmaceutical. The dose thereof is 0.3-5g/day, more preferably 2-4g/day administered in divided 3-4 portions.

Description

DETAILED DESCRIPTION OF THE INVENTION Field of Industrial Application The present invention provides a method for concentrating a herbal medicine containing Aochi or (and) Aochi or a mixture thereof under reduced pressure in the presence of water or cyclodextrin, and then concentrating the obtained concentrate. The present invention relates to a method for producing crude drug preparations (hereinafter sometimes abbreviated as the method of the present invention) characterized by spray drying.

The crude drug preparation obtained by the production method of the present invention is effective against gastric ulcers.

It is effective in treating gastritis, etc.

Conventionally, when producing crude drug preparations from crude drugs, there is a known method of drying and solidifying crude drug extracts or their concentrates in the presence of cyclodextrin. No drying equipment required,
However, the resulting powder has problems such as being extremely fine and having an extremely large specific volume, making it extremely difficult to formulate a formulation.

Means for Solving the Problems The present inventors have conducted extensive research to overcome these problems, and have found that using herbal medicines containing Soo or (and) Koboku, or mixtures thereof, with water or containing cyclodextrin. After extraction with water, the extract is concentrated under reduced pressure in the presence of cyclodextrin, and the resulting concentrate is spray-dried. It was discovered that a dry powder suitable for formulation can be obtained, and based on these findings, various studies were conducted, and as a result, the present invention was completed.

In the present invention, the term "extract liquid" refers to a soft extract obtained by an extraction operation.

The powder obtained by the method of the present invention has a composition that is not significantly different from that of an extract of a crude drug or a mixture thereof;
Moreover, it is a dry powder that is extremely stable against moisture and can be stored for a long period of time, and has a small specific volume, making it suitable for formulation.

The herbal medicine Maku containing Okibe or (and) Koboku used in the method of the present invention is at least Ao&
For t7t, it is sufficient to include (and) Hangboku, and in addition, chinpei, licorice, hussa, and A-fuzi.

dry life, large t, incense, martyrdom, keizhi, yankoshi, oyster kooka,
Good ship, Ephedra, Shushin, Gomaiko, ↑Natsu 9-choka.

A mixture of herbal medicines containing 11 or more of herbal medicines such as wood incense, agarwood, frankincense, persimmon obi, etc. is used, and the mixture of herbal medicines includes, for example, hirisosan, kasaheikusan, kasaheikusankakoku. Chinese medicine such as medicine is also used.

Here, Chinese herbal medicine refers to a combination of four types of herbal medicines according to a prescription that aims to produce "evidence" supported by theory of cold treatment, actual application of Chinese herbal prescriptions (Yamide Mitsutane), etc. For example, Kosa Heizoku Sanka Xun medicine is described in Chinese Medicine Clinical Practice, ζ9(5) 30 (1982).) Among the above, preferred are Hiasu San and Kosa Heizoku San.

These are Chinese herbal medicines such as fragrant sand flat stomach sanka xun medicine.

As the cyclodextrin used in the method of the present invention,
Acid tfC includes various cyclodextrins obtained by hydrolyzing starch with amylase.

As the cyclodextrin, for example, α (degree of polymerization 6
), β (degree of polymerization 7), and γ (degree of polymerization 8) are obtained (71fi/MaS'7 Vol, ILNal (19
80), Pharmaceutical Journal Vol. 1.101 (10).

857-873 (1981), Special Publication No. 53-31223
Please refer to the publication]. Among these, β-cyclodextrin is particularly preferred.

Each step of the method of the present invention will be explained below.

The extraction step is carried out by finely pulverizing the crude drug or mixture thereof containing the raw materials *han or (and) koboku, and then filtering it with water to obtain a filtrate. Cyclodextrin-containing water refers to a solution in which cyclodextrin is dissolved or suspended in water, and usually about m−→te→wt% of cyclodextrin is used.

About 2 to 10% of the water or cyclodextrin-containing water used for extraction, the raw herbal medicine or mixture thereof
0 times by weight, preferably about 4 to 30 times by weight, is often used. Depending on the category a of the raw herbal medicine or its mixture, cyclodextrin-containing water may be used instead of water to promote the extraction of the active ingredient. The temperature for extracting crude drugs containing Nambok is often in the range of room temperature to about 100°C, but is generally preferably in the range of 60 to 90°C.

The time required for extraction varies depending on the extraction temperature, but is generally about 30 minutes to 3 hours, preferably about 1 to 2 hours.

Vacuum concentration step When water is used as the extraction solvent, add water containing about 1 to 50% by weight of e~ζ phosphorus to the resulting aqueous extract, and when water containing cyclodextrin is used as the extraction solvent. The obtained extract is heated from room temperature to 60°C, and the solvent is distilled off under reduced pressure (for example, about 10 to 7 QQffilHg) to obtain a concentrate, that is, a soft extract in the form of a souffle (water content of about 20 to 50% by weight). Manufacture. The amount of cyclodextrin added to the aqueous extract is about 0.01 to 0.1 times the weight of the raw herbal medicine or mixture thereof.

The time required for vacuum concentration varies depending on the vacuum conditions, etc., but is generally about 30 minutes to 2 hours.

In this vacuum concentration, the temperature should not be raised above a certain temperature in order to prevent loss of contents, deterioration, etc.

Spray drying process In spray drying, the soft extract obtained in the above process is sprayed from a nozzle into a hot air stream after bending at 100 to 200°C, and drying is performed while the resulting atomized particles fall to the bottom. let At this time, the latent heat of vaporization of water is stimulated, so usually 3
The temperature remains at around 0 to 40°C, and no disadvantageous situation such as decomposition of the contents due to heat occurs.

In the dry powder obtained in this step, for example, one of the active ingredients contained in the tone hole in the raw herbal medicine or mixture of herbal medicines,
hineeol is one of the active ingredients contained in the compound represented by the formula, herbal medicine or mixture of herbal medicines, and magnol-IV (magnol).
olol) That is, the compound represented by the formula 0 formula%
It is stably held at around 80 seats.

The dry powder obtained in this way is a non-hygroscopic, free-flowing powder with a small specific volume, and can be used as a powder or fine granule.

Suitable for formulation of granules, 9 tablets, etc.

The dry powder thus obtained has low toxicity, can be administered orally, and contains known pharmaceutically acceptable excipients (for example, starch, lactose, phosphate, calcium phosphate, etc.), agents (e.g., starch, gum arabic, carboxymethylose, hydroxylose, hirseμlose.

crystallized mu-loose, etc.), a lubricant (e.g., magnesium stearate, /ri-mu-ritsu), a disintegrating agent (e.g., silicate, talc, synthetic aluminum silicate, etc.), It can be made into preparations such as Kadese μ preparations, powders, fine granules, granules, and tablets by conventional methods.

The crude drug preparations obtained according to the present invention can be used for the prevention and treatment of disease in the same way as decoctions made from conventional crude drugs. For example, for gastric ulcers and gastritis, the dosage for one adult is, for example, in the case of Hiisosan, Kosa Hiisosan, and Kosa Hiisosanka Koyaku, the crude drug preparation obtained by the present invention is administered at a daily dose of 0.3 to 591 mg. Preferably, 2 to 4 f can be given in 3 to 4 doses.

The present invention will be further explained in detail by showing 5jF examples below.

51! ! - Plum Blossom Viewing Example 1 5875 gj of water was added to Kosand Heimasuka Sankakuyaku Pharmaceutical Preparation 11759, and the mixture was stirred at 80°C for 1 hour. 1. Wash the insoluble matter once with warm water. When the filtrate and washing water are concentrated under reduced pressure under the same conditions, a soft extract (solid content concentration 40 weight *) s 9
8.5 tt is obtained. When this is spray-dried, 390 dry powders of Kasa Heizoku Sanka Ajiyaku are obtained (by the method below).

Dissolve 37.8jF (10-day prescribed amount) of the dry powder obtained above, add 250ml of water and 250ml of pharmacopoeia Diasta 2. After adding Of and dissolving it well, in a water bath (37
Decomposition of β-V clodextrin is carried out for 4 hours at ˜38° C. with occasional stirring. After extraction three times with 1 V50 al of diethyl ether at 3 h, the diethyl ether p layers are combined and dried over anhydrous sodium sulfate. After distilling off the solvent, the diethyl ether is determined. = After performing the same operation on the Hojoki extract, gas chromatography is measured under the same conditions to determine the content of hinesol.

■Gas chromatography measurement conditions Equipment: Gas Chroma Seven GrabE manufactured by Gas Chrom Industries.

Model 370 Column temperature increased from 280 to 250°C (5°C/e)
(Injection temperature: 200°C) Sensitivity = 1 × 8 Under these conditions, when holding Hinesaw μ, open for 22.5 minutes.

As a result of the above test, the retention rate of Hinesol was 6851! It was i.

As a comparison, when the same operation as above was performed without adding β-cyclodextrin to the extract, the dry powder was 330f.
(Hinesol retention rate of 596 or less) is obtained.

Thereafter, the retention rate of Hinesol in the dry powders obtained in Examples 2 to 4 was determined in the same manner as above.

Example 2 Water 3001 was added to fragrant sand flat stomach powder 5B, 75# and stirred at 78 to 80°C for 1 hour.

This is centrifugally filtered using a basket type fast core filter,
Wash once with warm water 801. Extract liquid 4031 is obtained by combining the filtrate and washing liquid. In this extract 383e, β
-Add 2.41 g of cyclodextrin and concentrate under reduced pressure under 40~b conditions to obtain soft extract 38 toge.

This soft extract and the previously obtained extract 201 are mixed,
When spray-dried, dry powder of fragrant sand flat stomach sanka xun medicine 14.5#
(Hinesso μ retention rate 6796) is obtained.

As a comparison, when the same operation as above was performed without adding β-cyclodextrin to the extract, the dry powder was 11.5%.
4 (Hineso! Retention rate 596 or less) is obtained.

Example 3 Kasa flat stomach sankaxun medicinal prescription 117.5f! , β-cyclodextrin 5f and water 587, 5sg were mixed, 80
Stir at ℃ for 1 hour. This was centrifugally filtered and the resulting liquid was measured by the Shear method under conditions of 40-45''C/70mag).

In addition, if the same operation as above is performed without adding β-cyclodextrin, 27 g of dry powder (hinesol retention rate 5
% or less).

Example 4 Blue: Add 50*j of water to 4CIOy and heat at 70°C for 1 hour.
Concentration under reduced pressure under the conditions of 0 to 45"C/70 WMHg and spray drying of the resulting soft extract yields 2.5f of dry powder of Blueberry (Hineso μ retention rate 6096).

Note that if this operation is performed after adding β-cyclodextrin to the extract, dry powder 1. El (Hineso/shi retention rate 5
96 or less) is obtained.

Procedural amendment (spontaneous) May 16, 1985 1. Indication of the case 1988 Patent Application No. 125690 2. Name of the invention Method for producing crude drug preparations 3. Person making the amendment Relationship to the case Patent applicant address Higashi, Osaka City Ward Doshomachi 2-27 Name (2
93) Takeda Pharmaceutical Co., Ltd. Representative Hayashi Kura
Iku Part 4 Agent address 2-17-85 Jusanhonmachi, Yodogawa-ku, Osaka City Column 6 of the detailed explanation of the invention in the specification subject to amendment, Contents of amendment (1) Specification, page 13, line 14 Insert the following sentence between and line 16 of the same page.

[Example 5 425 g of water was added to 85 g of flat stomach dispersion and stirred at 80°C for 1 hour. After filtration, insoluble matter is washed once with warm water. To the extract obtained by combining the filtrate and washing water, a solution of 37 g of β-cyclodextrin in 200 g of water was added, and then 40 g of
Concentration under reduced pressure at 150 mmHg at °C yields 41.0 g of soft extract (solid content 40% by weight). When this is spray-dried, 20.1 g of dry powder of Heisosan (Hinesol retention rate: 77%) is obtained.

As a comparison, when the same operation as above was performed without adding β-cyclodextrin to the extract, the dry powder was 16.5%.
g (Hinesol retention rate of 5% or less) is obtained.

Example 6 Add 362 g of water to 51.75 g of Kasa flat stomach dispersion, and add 80 g of water.
Stir at ℃ for 1 hour. After filtration, insoluble matter is washed once with warm water. β-
Add a solution of 2.9 g of cyclodextrin in 200 ml of water,
The mixture is then concentrated under reduced pressure at 40° C. and 150 mmHg to obtain 36.0 g of soft extract (solid content concentration: 40% by weight). When this is spray-dried, dry powder of Kasa Heisosan is obtained.9.
0 g (Hinesol retention rate of 60%) is obtained.

As a comparison, when the same procedure as described in ``-'' was performed without adding β-cyclodextrin to the extract, 77 g of dry powder was obtained.
(Hinesol retention rate of 5% or less) is obtained. ” (2) “2-4” on page 11, line 12 of the same book is replaced with “2-6”
Correct.

that's all

Claims (1)

[Claims] The herbal medicine containing Aochi or (and) Aoba or a mixture thereof is extracted with water or cyclodextrin-containing water, the extract is concentrated under reduced pressure in the presence of cyclodextrin, and the resulting concentrate is then spray-dried. Characteristic manufacturing method of crude drug preparations.