JP2013071935A - Agglomerated material containing tinged shimotsuto extract powder - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an agglomerated material containing tinged Shimotsuto extract powder that has high moldability during production and excellent disintegration.SOLUTION: This agglomerated material containing tinged Shimotsuto extract powder that is formulated using the tinged Shimotsuto extract powder together with stearate can obtain high moldability during production and excellent disintegration.

Description

  The present invention relates to a granulated product containing a kamitsumonoyu extract powder. More specifically, the present invention relates to a granulated product containing a kamishitsuto extract powder having excellent moldability during production and good disintegration.

  Traditionally, herbal medicines have been used as traditional Chinese medicines, and their prescriptions have been described in many classics (many disease recovery, wound cold theory, Jin Yong outline, etc.) as accumulated experience over many years. However, in accordance with the classics, decoction that is cut from herbal medicine and decocted with water to extract ingredients in herbal medicine is not only difficult to take due to its unique medicinal odor and taste, but also must be prepared each time it is taken. This requires a lot of work and time. Therefore, today, a herbal medicine extract is used as an easy-to-use Chinese medicine preparation that saves the trouble of preparation at the time of use. Usually, a herbal medicine extract is obtained by extracting a herbal medicine that has been cut out with an extraction solvent such as water or alcohol, and concentrating and drying the extract to obtain a herbal medicine extract powder. It is manufactured by a method of forming a mold (for example, tablet, capsule, powder, fine granule, granule, etc.).

  Conventionally, a wet granulation method and a dry granulation method are known as techniques for formulating herbal extract powder into tablets, granules, fine granules and the like. The wet granulation method is a method for obtaining a granulated product by mixing and granulating with a solvent and then drying to obtain a granulated product, which requires heating at a high temperature when the solvent is removed, and is included in the herbal medicine extract powder Due to the disadvantage that active ingredients may be lost, it is generally considered unsuitable for the method of manufacturing Chinese herbal extract powder. On the other hand, the dry granulation method does not use a solvent during mixing and granulation, and therefore, there is no loss of active ingredients due to high-temperature heating. Therefore, the dry granulation method is suitable as a method for producing herbal extract powder. Are widely employed in the manufacture of non-patent documents (see, for example, Non-Patent Document 1, Patent Document 1, etc.).

  However, since the Chinese herbal extract powder has different physical properties such as hygroscopicity and stability depending on the type, the common prescription and granulation method cannot be applied to all herbal medicine extracts. In particular, it is known that the Kamitsumonoyu extract powder has a very high hygroscopic property and a unique property that the moldability is poor. Therefore, in the case of using the Kamitsumonoto extract powder by dry granulation, it is necessary to add a large amount of excipients to improve its hygroscopicity and moldability in the conventional technique. ing.

  However, if a large amount of excipients is added to the Kamitsumonotsuto extract powder and granulated, the granulated material collapses due to the inclusion of a large amount of excipients, even though the defects in moldability can be improved. Time delay is a problem.

  Thus, in the prior art, there is no formulation technology for a granulated product containing Kamitsuyuto extract powder that has excellent moldability at the time of manufacture and good disintegration, and the provision of the granulated product is not provided. The current situation was not realized.

Nakai, Y., Medicinal Development, Volume 11, Single Operation and Machine, 48-49, Yodogawa Shoten, 1989

JP-A-3-24019

  An object of the present invention is to provide a granulated product containing Kamitsuyuto extract powder that has excellent moldability during production and has good disintegration properties.

  The present inventor made extensive studies to solve the above problems. Surprisingly, a granulated product containing a kamitsuyuto extract powder formulated with a combination of a kamitsuyuto extract powder and a stearate. Has been found to be excellent in moldability during production and have good disintegrability. Furthermore, it has also been found that the disintegration property of the granulated product containing the Kamijoto extract powder can be further improved by blending sucrose fatty acid ester with the above components. The present invention has been completed by further studies based on this finding.

That is, this invention provides the granulated material of the aspect hung up below.
Item 1. A granulated product comprising a kamitsumonoyu extract powder and a stearate.
Item 2. Item 2. The granulated product according to Item 1, wherein the content of stearate is 2 to 5% by weight based on the total amount of the granulated product.
Item 3. Item 3. The granulated product according to Item 1 or 2, wherein the stearate is magnesium stearate.
Item 4. Item 4. The granulated product according to any one of Items 1 to 3, further comprising a sucrose fatty acid ester.
Item 5. Item 5. The granulated product according to Item 4, wherein the fatty acid constituting the sucrose fatty acid ester has 12 to 22 carbon atoms.
Item 6. Item 6. The granulated product according to Item 4 or 5, wherein the sucrose fatty acid ester has an HLB value of 10 or more.
Item 7. Item 7. The granulated product according to any one of Items 4 to 6, wherein sucrose fatty acid ester is contained at a ratio of 0.1 to 5 parts by weight per 1 part by weight of stearate.

  While the granulated product of the present invention contains the Kamitsuyuto extract powder having very high hygroscopicity, the moldability at the time of production is remarkably improved, and the production loss that occurs during granulation can be suppressed. High production efficiency can be realized in the production.

  Moreover, the granulated product of the present invention has a good disintegration property, and after taking it, it is possible to effectively exhibit the desired effect of the Kamitsuyuto extract powder in the body.

  The granulated product of the present invention is characterized in that it contains a kamijoyuto extract powder and a stearate. Hereinafter, the present invention will be described in detail.

  Kami-Yomono-to is described in the Chinese medical era “Manju Rejuvenated” and is often used to improve lower extremity muscle weakness, neuralgia, swelling and pain of joints, rheumatoid arthritis, arthritis, etc. It is a prescription. Kami Shimonoto is a mixed herbal medicine that includes Toki, Kawakyu, Shakuyaku, Ji-Huang, Sakai, Mumon-Winter, Ginseng, Beef-Knee, Jasmine, Gomi-ko, Huang Ren, My Mom, and Tochu. Here, Toki refers to the roots of the ciraceae sugar beet; Kawakyu refers to those obtained by blanching the rhizome of the ciraceae senkyu; glaze refers to the roots of the button family peonies;蒼朮 is the root of Asteraceae, such as Asteraceae; the roots of Lilyaceae janohige, etc .; the carrot is the root of Panax ginseng; the cow knee is the root of Amaranthus japonica, etc .; Is the roots excluding the citrus yellowfin skin; Gomiko is the fruit of the Chrysanthemum family ginseng; the yellow stem is the rhizome of the buttercup family Auren, etc .; It is the bark of the eucommia eucommia. In addition, among the herbal medicines contained in the Kami four hot waters, persimmon may be replaced or used in combination with birch (Asteraceae rhizome). In the present invention, the mixing ratio of each herbal medicine contained in the Kamitsu four-boiled water is not particularly limited, but usually 2.5 to 3 for the weight, 2 to 3 for the river, 2 to 3 for the glaze, and the ground yellow 3-8, cocoon 3 (2.5 in the case of white cocoon), baron winter 2.5-5, carrot 1.5-2.5, cow knee 1-2.5, jaundice 1.5, gomisiko 1 1.5, Huang Ren 1.5, known mothers 1-1.5, and Tonaka 1.5-2.

  The “Kamitsu four hot water extract powder” used in the present invention is a dry extract powder obtained by subjecting an extract obtained by subjecting the Kami four hot water to an extraction treatment or a concentrated solution thereof to a drying treatment. Below, the extraction and drying conditions of Kamitsu four hot water will be described.

  Although it does not restrict | limit especially as an extraction solvent used for the extraction process of Kamijomonoyu, For example, water, ethanol, an acetic acid, and these liquid mixture are mentioned.

  There are no particular restrictions on the extraction conditions for Kamitsumonoyu, but for example, 5 to 25 times, preferably 10 to 20 times the amount of extraction solvent is added to the total weight (in terms of dry weight) of Kamiyotoyu. In addition, there is usually a method of incubating at 70 to 100 ° C. for 1 to 2 hours to heat decoction.

  The thus-obtained Kamitsuyuto extract is subjected to a drying treatment after removing solids by filtration or the like and concentrating as necessary. A method for drying the extract of the Kamitsu four hot water or the concentrated solution thereof is not particularly limited, and examples thereof include spray drying, vacuum concentration drying, freeze drying, and the like. Among these drying methods, the spray drying method is preferable.

  In the case of subjecting the Kamitsumonoyu extract to a drying treatment (particularly, a drying treatment by spray drying), it is desirable to add an excipient to the Kamitsumonoyu extract. Thus, by adding an excipient | filler, while shortening drying time, it also becomes possible to reduce the hygroscopic property of the seasoned four hot water extract powder after drying. The excipient added during the drying process of the Kamitsumonoto extract is not particularly limited as long as it is pharmaceutically acceptable. For example, silicic anhydride, hydrous silicon dioxide, aluminum silicate, silica Inorganic excipients such as magnesium aluminate, magnesium aluminate, silica, titanium oxide, etc .; celluloses such as cellulose, carboxymethylcellulose, methylserose, hydroxypropylcellulose; starches such as starch and hydroxypropyl starch; dextrin, Examples include gelatin. These excipients may be used alone or in combination of two or more.

  The amount of excipient added during the drying process of the Kamitsu Yotsuyu extract (that is, the amount of excipient contained in the Kamitsu Yotsuyu extract powder) is not particularly limited. The excipient is 5 to 70 parts by weight, preferably 20 to 50 parts by weight, per 100 parts by weight of the dry weight of the four-product hot water extract.

  In the granulated product of the present invention, the content of the above-mentioned Kamitsuyuto extract powder is not particularly limited. For example, the total amount of the granulated product is 10 in terms of the dry extract of the Kamijotoyu extract powder. -85 weight%, Preferably it is 20-80 weight%, More preferably, 30-70 weight% is mentioned. In the present specification, the dry extract amount of the Kamitsumonoyu extract powder is the amount of components derived from the Kamitsumonoyu extract powder. When it is contained, it is a value converted by excluding the excipient content.

  The granulated product of the present invention contains a stearate salt together with the above-mentioned Kamishitokuyu extract powder. Thus, by including a stearate, it becomes possible to improve the moldability at the time of manufacture remarkably and to have a good disintegration property.

  The stearate used in the present invention is not particularly limited as long as it is pharmaceutically acceptable, and examples thereof include magnesium stearate, calcium stearate, aluminum stearate, zinc stearate and the like. Among these, magnesium stearate is preferable from the viewpoint of further improving the moldability during production and the disintegration property of the granulated product.

  In the granulated product of the present invention, the content of stearate is not particularly limited, but is preferably 2 to 5% by weight based on the total amount of the granulated product. In particular, when the content of stearate satisfies 2.5 to 5% by weight, the moldability during production can be remarkably improved while providing excellent disintegration in the granulated product. It is suitable as the content of stearate in the present invention. Conventionally, stearates have been used as lubricants in pharmaceutical preparations. For example, magnesium stearate causes molding inhibition and poor collapse of molded products due to excessive addition or mixing (Tsuda Keisuke et al. (See Pharmaceutical Development Basic Course X “18 Formulation Engineering”, pages 170-173, Jinshokan (1971); Kuichi Sunada et al., Research on Granules for Tableting, PHARM TECH JAPAN, 9, 1139, (1993)) About 0.1 to 1% by weight is blended. On the other hand, the content of stearates in the present invention far exceeds conventional blending amounts, and differs from conventional lubricants in both the purpose and the preferred content.

  In the granulated product of the present invention, the ratio of the stearate to the Kamitsumonoyu extract powder is not particularly limited. For example, the stearic acid is 1 part by weight in terms of the dry extract amount of the Kamijotoyu extract powder. 0.01 to 0.5 parts by weight of salt, preferably 0.025 to 0.5 parts by weight, more preferably 0.05 to 0.5 parts by weight, still more preferably 0.06 to 0.5 parts by weight, Particularly preferred is 0.06 to 0.25 parts by weight.

  The granulated product of the present invention can contain a sucrose fatty acid ester in addition to the above components. By containing the sucrose fatty acid ester, it is possible to further improve the disintegration property of the granulated product while maintaining excellent moldability during production.

  The type of sucrose fatty acid ester used in the present invention is not particularly limited. For example, sucrose laurate, sucrose myristic ester, sucrose palmitate, sucrose stearate, sucrose arachidic acid Examples thereof include sucrose behenic acid ester, sucrose capric acid ester, sucrose palmitic acid ester, sucrose oleic acid ester, and sucrose linoleic acid ester. Among these sucrose fatty acid esters, from the viewpoint of further improving the disintegration property of the granulated product, the constituent fatty acids of the sucrose fatty acid ester are preferably 12 to 22 carbon atoms, more preferably 14 to 20 carbon atoms, Particularly preferred are those having 16 to 18 carbon atoms.

  Moreover, as an HLB value of the sucrose fatty acid ester used by this invention, from a viewpoint of improving the disintegrating property of a granulated material further, Preferably it is 10 or more, More preferably, 11-16 is mentioned.

  In this invention, sucrose fatty acid ester may be used individually by 1 type, and may be used in combination of 2 or more type.

  When the sucrose fatty acid ester is contained in the granulated product of the present invention, the ratio of the stearate and the sucrose fatty acid ester is not particularly limited, but from the viewpoint of further improving the disintegration property of the granulated product, The amount of sucrose fatty acid ester is preferably 0.1 to 5 parts by weight, more preferably 0.25 to 4 parts by weight, and particularly preferably 0.5 to 3 parts by weight per 1 part by weight of stearate.

  When the sucrose fatty acid ester is contained in the granulated product of the present invention, the content of the sucrose fatty acid ester is not particularly limited, and is appropriately set according to the ratio of the stearate to the sucrose fatty acid ester described above. Is done. For example, the content of sucrose fatty acid ester is usually 0.01 to 20% by weight, preferably 0.1 to 15% by weight, more preferably 0.5 to 10% by weight, based on the total amount of the granulated product. Preferably 0.75 to 10 weight% is mentioned.

  The granulated product of the present invention can also contain an excipient. The excipient that can be blended in the granulated product of the present invention is not particularly limited as long as it is pharmaceutically acceptable. For example, sugars such as lactose, glucose, maltose, sucrose, and sucrose: mannitol, sorbitol, xylitol, Sugar alcohols such as trehalose and erythritol; starches such as corn starch, potato starch, wheat starch, rice starch, pregelatinized starch, dextrin, carboxymethyl starch and derivatives thereof; cellulose, crystalline cellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, carboxy Cellulose and its derivatives such as methylcellulose; gum arabic, dextran, pullulan, light anhydrous silicic acid, synthetic aluminum silicate, magnesium aluminate metasilicate, calcium phosphate, calcium carbonate, Calcium, crospovidone, croscarmellose sodium, carmellose calcium, and the like. These excipients may be used alone or in combination of two or more. Among these excipients, saccharides are preferable, and lactose is more preferable.

  When the granulated product of the present invention contains an excipient, the content of the excipient is not particularly limited. For example, it is usually 5 to 75% by weight, preferably 10%, based on the total amount of the granulated product. -50% by weight, more preferably 15-40% by weight.

  In addition, the granulated product of the present invention may further contain a disintegrant, a lubricant, a binder, a preservative, a sour agent, a sweetener, a fragrance, a colorant, and the like as necessary.

  Although it does not restrict | limit especially about the average particle diameter of the granulated material of this invention, For example, 100-2000 micrometers, Preferably it is 250-1500 micrometers, More preferably, 300-1000 micrometers is mentioned. Here, the average particle size of the granulated product is a particle size of 50% by weight when performing according to the screening method of the particle size measurement method of the 15th revision Japanese Pharmacopoeia.

  The granulated product of the present invention can be produced, for example, by a granulation method such as a dry granulation method or a heat granulation method. Among these granulation methods, the dry granulation method (especially, the dry granulation method using a roller compactor is used to reduce the heat load, improve the moldability of the granulated product of the present invention, and perform efficient production. ) Is preferred.

  The granulated product of the present invention can be provided as it is as a granule or a fine granule, but if necessary, it can be provided as a coating preparation by coating with a water-soluble polymer or filled into a capsule. It can also be provided as a capsule. Furthermore, the granulated product of the present invention may be further provided for tableting by tableting.

  The granulated product of the present invention is used as a Chinese medicine preparation for improving lower extremity muscle weakness, neuralgia, joint swelling and pain, rheumatoid arthritis, arthritis and the like.

  The Kampo preparation containing the granulated product of the present invention can be orally administered per day or divided into 1000 to 6000 mg per day in terms of the dry extract amount of Kamishitokuto extract powder. , Age, weight, symptom degree, etc. can be adjusted as appropriate.

  Hereinafter, the present invention will be described in detail based on examples and the like, but the present invention is not limited thereto.

Test example 1
1. Manufacture of Kamitsumonoyu extract powder 3 parts by weight, 3 parts by weight of river cucumber, 3 parts by weight of glaze, 3 parts by weight of ground yellow, 3 parts by weight of straw, 5 parts by weight of Mumon winter, 2.5 parts by weight of carrot, beef 10 parts by weight of 2.5 parts by weight of the knee, 1.5 parts by weight of jaundice, 1.5 parts by weight of gouriko, 1, 5 parts by weight of the yellow chain, 1.5 parts by weight of the mother, and 1.5 parts by weight of Tonaka. Heat extraction was performed for about 1 hour using double amount of water. The obtained extract was collected by filtration.

  The obtained extract was concentrated under reduced pressure at 70 ° C. or lower, added with an appropriate amount of excipient, dried by spray drying, and added to Kamitsutoyu extract powder (70% by weight of dry extract of Kamijotoyu, 30% by weight of excipient) was obtained.

2. Manufacture of granulated product After mixing the Kamitsuyuto extract powder obtained above, magnesium stearate, and lactose in the proportions shown in Table 1, compression molding with a roller compactor (Freund Sangyo Co., Ltd.) Granules were obtained by grinding using a roll granulator. The average particle diameter of the obtained granules was 600 to 900 μm.

3. Evaluation of moldability and disintegration At the time of granule production, the degree of adhesion of the raw material to the roll of the roller compactor was visually observed, and the moldability was evaluated according to the following criteria.
<Criteria for moldability>
5: Adhesion of the raw material to the roll was not recognized at all, and compression molding / pulverization could be performed without any problem.
4: The raw material was slightly attached to the roll, but there was almost no influence on compression molding, and compression molding / pulverization could be performed without any problem.
3: The raw material adhered to the roll, resulting in production loss during compression molding, and the production efficiency of the compression molded product by the roller compactor was reduced, but compression molding / pulverization could be performed.
2: The amount of raw material attached to the roll is large, and over time, the production efficiency of the compression molded product by the roller compactor decreases, and finally, all the raw materials cannot be made into a compression molded product. It was.
1: The adhesion of the raw material to the roll was remarkable, and a compression molded product with a roller compactor could not be produced.

  Further, the granules obtained above were evaluated for disintegration according to the 16th revised Japanese Pharmacopoeia disintegration test method. Specifically, 0.10 g of the granules remaining on the No. 30 sieve were put in an auxiliary cylinder, the test machine was operated using water at 37 ± 2 ° C. as a test solution, and the collapse time was measured.

4). Results The results obtained are shown in Table 1. As is apparent from Table 1, when granulation was performed without blending magnesium stearate (Comparative Example 1), the moldability was remarkably poor and the granule could not be produced. In the case of granulation (Example 1-5), the moldability was improved, and granules could be produced with high production efficiency. In particular, when the content of magnesium stearate was 2% by weight or more, particularly 2.5 to 4% by weight, the moldability was remarkably excellent. Moreover, it was also confirmed that the granule (Example 1-5) which mix | blended magnesium stearate has disintegration time within 30 minutes and is equipped with favorable disintegration property.

In Example 3, when granules were prepared using calcium stearate or aluminum stearate instead of magnesium stearate, granules excellent in moldability and disintegration could be obtained. However, in terms of moldability and disintegration, the granules containing magnesium stearate were particularly excellent.
On the other hand, when granules were prepared using talc instead of magnesium stearate in Example 3, it was not possible to obtain granules excellent in both moldability and disintegration.

Test example 2
After mixing the Kamitsumonoyu extract powder, magnesium stearate, sucrose stearate and lactose prepared in Test Example 1 in the proportions shown in Table 2, and compression-molding with a roller compactor (Freund Sangyo Co., Ltd.) Granules were obtained by grinding using a roll granulator. The average particle diameter of the obtained granules was 600 to 950 μm. The moldability during granule production and the disintegration property of the granules were evaluated by the same method as in Test Example 1.

  The obtained results are shown in Table 2. From this result, it was confirmed that by adding sucrose stearate in addition to the Kamitsumonoyu extract powder and magnesium stearate, the disintegration property can be further improved while maintaining excellent moldability ( Example 6-13). In particular, when sucrose stearate is contained at a ratio of 0.166 to 4 parts by weight, particularly 0.25 to 3 parts by weight per 1 part by weight of magnesium stearate, the disintegration is remarkably improved. It became clear to do.

Test example 3
Kamijotsuyu extract powder prepared in Test Example 1, magnesium stearate, various sucrose fatty acid esters and lactose shown in Table 3 were mixed at the ratio shown in Table 3, and compressed with a roller compactor (Freund Sangyo Co., Ltd.). After molding, granules were obtained by grinding using a roll granulator. The average particle diameter of the obtained granules was 500 to 900 μm. The moldability during granule production and the disintegration property of the granules were evaluated by the same method as in Test Example 1.

  The obtained results are shown in Table 3. From this result, it was confirmed that even when the carbon number of the fatty acid constituting the sucrose fatty acid ester was changed, the disintegration property could be further improved as in the result of Test Example 2. In particular, from this result, when the number of carbon atoms of the constituent fatty acid of the sucrose fatty acid ester is 16 to 18 or when the HLB value of the sucrose fatty acid ester is 11 or more (Examples 15, 16 and 18), it is remarkably remarkable. It was also confirmed that the disintegration property can be improved.

Formulation Examples Tables 4 to 6 below show Formulation Examples 1 to 18 relating to the granulated product of the present invention. A granulated product having the composition shown in Formulation Examples 1 to 18 was prepared by a conventional method using the Kamitsuyumono extract powder prepared in Test Example 1. When these granules were subjected to the same test as in Test Example 1, it was confirmed that the granules were excellent in moldability during production and had good disintegration properties.

Claims (7)

  A granulated product comprising a kamitsumonoyu extract powder and a stearate.   The granulated product according to claim 1, wherein the content of stearate is 2 to 5% by weight based on the total amount of the granulated product.   The granulated product according to claim 1 or 2, wherein the stearate is magnesium stearate.   Furthermore, the granulated material in any one of Claims 1-3 containing a sucrose fatty acid ester.   The granulated product according to claim 4, wherein the fatty acid constituting the sucrose fatty acid ester has 12 to 22 carbon atoms.   The granulated product according to claim 4 or 5, wherein the sucrose fatty acid ester has an HLB value of 10 or more.   The granulated product according to any one of claims 4 to 6, wherein sucrose fatty acid ester is contained at a ratio of 0.1 to 5 parts by weight per 1 part by weight of stearate.