JP2012062279A - High-unit glucosamine granule for direct striking - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide granulated powder or granules with a high content of glucosamine, which is excellent enough in liquidity for practical use and suitable for tablet processing.SOLUTION: The granulated powder or granules contains (a) glucosamine or a salt thereof, and (b) at least one lubricant selected from the group consisting of calcium phosphate, fine grain silicon dioxide, calcium stearate, and magnesium stearate.

Description

  The present invention relates to a granulated powder or granule containing a high content of glucosamine, and a method for producing the same.

  Glucosamine is one of the components constituting the living body and is a monomolecular amino sugar. Glucosamine is produced by chondrocytes and promotes the production of cartilage components. Therefore, glucosamine is effective for arthritis such as osteoarthritis and is on the market as a supplement for nutritional supplementation.

There are various forms of glucosamine intake, and one of them is the tablet, which is easy to carry and can be taken without measuring the amount at the time of intake. This is one of the forms.
However, the crystal powder of glucosamine and its salt has a problem of poor tabletability. In other words, crystal powder generally has poor fluidity, poor uniform filling into the die of a tableting machine, frequency of occurrence of tableting troubles such as capping and lamination, and variation in tablet weight. This will cause problems. In addition, when the glucosamine or its salt crystal powder is once granulated and used for tableting, if the content of glucosamine is increased, the fluidity is poor and it is difficult to produce granules suitable for direct compression. Therefore, it was difficult to produce a high content tablet.

  Regarding such a problem, for example, Patent Document 1 discloses that the binding property is improved by using a powder of glucosamine or a salt thereof as a pulverized product, and can be suitably used as a tablet composition. Furthermore, Patent Document 1 discloses that the use of both a pulverized product having a high binding property and a crystal powder having a low binding property improves the fluidity of the tablet composition, and the frequency of occurrence of tableting troubles. It can be kept low, and it can be suitably used as a tablet composition.

  Patent Document 2 is suitable for tableting process by granulating after spraying a solution containing saccharides such as starch, polysaccharides and monosaccharides other than glucosamine to glucosamine or while spraying. It is disclosed that glucosamine granules having excellent physical properties can be obtained.

JP-A-2005-225787 JP 2006-36644 A

  However, the glucosamine crystal pulverized material-containing composition of Patent Document 1 is not practically sufficient for improving fluidity. In addition, in order to obtain physical properties suitable for tableting, the method of Patent Document 2 requires spraying a very large amount of a saccharide solution on glucosamine, which requires a long time for granulation and is expensive to produce. There are problems such as becoming.

  Accordingly, an object of the present invention is to avoid the problems existing in the above prior art, and to produce granulated powder or granules containing a high content of glucosamine, which is practically sufficiently fluid and suitable for tableting, and its production It is to provide a method.

In order to achieve the above-mentioned object, the present inventor has conducted research, and (a) at least one selected from the group consisting of glucosamine or a salt thereof and (b) calcium phosphate, fine silicon dioxide, calcium stearate, and magnesium stearate. It has been found that the composition containing the above-mentioned lubricant is very excellent in fluidity when granulated into granules, and is difficult to cause tableting troubles. Moreover, even when the content rate of glucosamine is high, this composition can be made into the granulated powder or granule which is excellent in fluidity | liquidity, As a result, it discovered that the tablet containing high glucosamine content could be manufactured efficiently.
This invention is completed based on the said knowledge, and provides the following granulated powder or granule, and its manufacturing method.

Item 1. A granulated powder or granule containing (a) glucosamine or a salt thereof, and (b) at least one lubricant selected from the group consisting of calcium phosphate, fine silicon dioxide, calcium stearate, and magnesium stearate.
Item 2. Item 2. The granulated powder or granule according to Item 1, wherein the lubricant is calcium phosphate.
Item 3. Item 3. The granulated powder or granule according to item 1 or 2, wherein the content of glucosamine or a salt thereof is 90 to 99.9% by mass as glucosamine with respect to the total mass of the granulated powder or granule.
Item 4. Item 4. The granulated powder or granule according to any one of Items 1 to 3, wherein the glucosamine or a salt thereof is glucosamine or a salt thereof whose primary particles have a volume average particle diameter of 3 to 200 µm.
Item 5. Item 5. The granulated powder or granule according to any one of Items 1 to 4, wherein the lubricant content is 0.1 to 10% by mass relative to the total mass of the granulated powder or granule.
Item 6. The step of mixing glucosamine or a salt thereof with (b) at least one lubricant selected from the group consisting of calcium phosphate, fine silicon dioxide, calcium stearate, and magnesium stearate, and granulating the resulting mixture The manufacturing method of the granulated powder or granule in any one of claim | item 1 -5 including a process.

  Since the granulated powder or granule of the present invention has a high content ratio of glucosamine and extremely good fluidity, a tablet having a high content of glucosamine can be produced without causing tableting trouble.

Hereinafter, the present invention will be described in detail.
(I) Granulated powder or granule The granulated powder or granule of the present invention is at least selected from the group consisting of (a) glucosamine or a salt thereof and (b) calcium phosphate, fine silicon dioxide, calcium stearate, and magnesium stearate. A granulated powder or granule containing one type of lubricant.

(a) Glucosamine Glucosamine is a natural amino acid and is widely distributed as a constituent of mucopolysaccharides in cartilage, connective tissue, and the like in animals. It is also abundant in crustacean chitin such as crabs and shrimps.
In the present invention, glucosamine may be used as glucosamine itself, but may have a salt form. Glucosamine salt is easily absorbed from the intestinal tract after ingestion. Examples of the glucosamine salt include inorganic acid salts such as glucosamine sulfate and glucosamine hydrochloride; organic acid salts such as N-acetylglucosamine. Of glucosamine and glucosamine salt, glucosamine salt is preferable because it is stable to heat and hardly browned, and glucosamine hydrochloride is more preferable.

Glucosamine and its salt may be either crystalline or amorphous. Although it is difficult to produce granules with good fluidity, according to the present invention, granulated powder or granules with good fluidity can be obtained even with glucosamine crystals. Therefore, in the present invention, glucosamine crystals and crystal powders can be suitably used.
The purity of glucosamine and its salt is preferably 98% or more, and more preferably 99% or more. The loss on drying of glucosamine is preferably 0.3% or less, more preferably 0.1% or less.
Since glucosamine and its salt are produced by microbial fermentation using plants as raw materials, for example, they are sold by Kyowa Hakko Bio Co., Ltd. and Kyowa Wellness Co., Ltd., so such commercial products can be purchased.
Glucosamine and its salt can be prepared, for example, by extracting chitin from shrimp or crab shells, hydrolyzing it, and purifying it. Furthermore, glucosamine hydrochloride and sulfate can be produced by using chitin as a raw material according to the methods described in JP-A No. 2004-359908 and US Pat. No. 3,683,076. N-acetylglucosamine can be produced by using chitin as a raw material according to the methods described in Japanese Patent Publication No. 5-33037 and Japanese Patent Application Laid-Open No. 2000-281696. Glucosamine (including glucosamine salt) derived from shrimp and crab is commercially available from, for example, Fuso Chemical Industry Co., Ltd., Saneigen FFI Co., Ltd., and Nakahara Co., Ltd. can do.

As the glucosamine and its salt in the present invention, commercially available glucosamine and glucosamine salt, glucosamine obtained by hydrolysis and purification of chitin, etc. may be used as they are, or may be used after pulverization. The pulverization method may use any principle of compression, impact or shear due to external force, and collision or friction due to inertial force of the particles themselves. For example, a ball mill (specifically, a rolling ball mill, a planetary mill, etc.), a roller mill (specifically, a solid roller mill, a roll crusher, a high-pressure roll press, etc.), a high-speed rotary mill (specifically, a hammer) Mill, pin mill, cage mill, etc.), jet mill and the like.
As for glucosamine, the volume average particle diameter of primary particles is preferably about 3 to 200 μm, and more preferably about 5 to 100 μm. If the volume average particle diameter of the primary particles of glucosamine is in the above range, the decrease in yield due to particles escaping from the bag filter when drying with a fluidized bed granulation dryer is suppressed, and tableting troubles are avoided. Is done.
In the present invention, the volume average particle diameter is a value measured using a laser diffraction / scattering particle size distribution analyzer LMS-350 (Seishin Enterprise).

  The content of glucosamine and its salt in the granulated powder or granule of the present invention is about glucosamine with respect to the total mass of the granulated powder or granule (that is, in the case of a glucosamine salt, converted to glucosamine weight). It is preferably 90 to 99.9% by mass, more preferably about 93 to 99% by mass, and further preferably about 95 to 98.5% by mass.

(b) Lubricant The calcium phosphate, fine silicon dioxide, calcium stearate, and magnesium stearate in the present invention are not particularly limited as long as they can be used in foods, medicines and the like. Examples of calcium phosphate include tricalcium phosphate (also known as tricalcium phosphate), calcium hydrogen phosphate, calcium dihydrogen phosphate, and the like. Among these, tricalcium phosphate is preferable. Examples of the fine silicon dioxide include fine silicon dioxide conforming to food additive standards, hydrous silicon dioxide conforming to pharmaceutical additive standards, and the like.
Among the lubricants of component (b), calcium phosphate and fine silicon dioxide are preferable, and calcium phosphate is more preferable.
Commercial products of calcium phosphate, fine silicon dioxide, calcium stearate, and magnesium stearate can be purchased.

The content of the lubricant of the component (b) in the granulated powder or granule of the present invention is not particularly limited as long as it is within the range of the general use in the granule preparation for tablet production. Or it is preferable that it is about 0.1-10 mass% with respect to the total mass of this granule, It is more preferable that it is about 0.5-5 mass%, It is further more preferable that it is about 0.8-2 mass%.
In addition, when using calcium phosphate and / or calcium stearate as component (b), the content of component (b) in the granulated powder or granule is such that the calcium content in the granulated powder or granule is in the food. The amount is preferably 1% by mass or less, which is the calcium content standard.

Other Additives The granulated powder or granule of the present invention optionally contains other additives such as sugars, sweeteners, acidulants, binders, antioxidants, colorants, fragrances, and disintegrants. Also good.

The saccharide is not particularly limited as long as it can be used for food, medicine, and the like, and examples thereof include monosaccharide, disaccharide, sugar alcohol, oligosaccharide and the like.
Examples of monosaccharides include glucose, xylose, galactose, fructose, and mannose. Examples of the disaccharide include trehalose, sucrose, lactose, palatinose, cellobiose, maltose and the like. Examples of the sugar alcohol include maltitol, erythritol, sorbitol, xylitol and the like. Examples of the oligosaccharide include raffinose, inuro-oligosaccharide (chicory oligosaccharide), palatinose oligosaccharide, fructo-oligosaccharide, xylo-oligosaccharide, and galacto-oligosaccharide. Of these, disaccharides and sugar alcohols are preferable, trehalose and sucrose are more preferable as disaccharides, and maltitol and erythritol are more preferable as sugar alcohols.

  The shape of the saccharide is not particularly limited, but is preferably in the form of microcrystals or fine particles, and the average particle size thereof is, for example, about 1 to 100 μm, preferably about 5 to 80 μm, more preferably about 10 to 60 μm, and particularly preferably about 30. ~ 50 μm. The content of the saccharide when the granulated powder or granule of the present invention contains a saccharide is not particularly limited as long as it is within the range of general use in the preparation.

  The sweetening agent is not particularly limited as long as it can be used for food, medicine, and the like, and examples thereof include sodium saccharin, dipotassium glycyrrhizin, aspartame, stevia, thaumatin and the like. Among these, stevia is preferable. When the granulated powder or granule of the present invention contains a sweetener, the content of the sweetener is not particularly limited as long as it is within the range of general use in the preparation.

  The acidulant is not particularly limited as long as it can be used for foods and medicines, and examples thereof include citric acid, tartaric acid, malic acid and the like. Of these, citric acid is preferred. The content of the acidulant in the case where the granulated powder or granule of the present invention contains an acidulant is not particularly limited as long as it is within the range of general use in the preparation.

  The binder is not particularly limited as long as it can be used for food, medicine, and the like, and examples thereof include gelatin and pullulan. Of these, pullulan is preferred. When the granulated powder or granule of the present invention contains a binder, the content of the binder is not particularly limited as long as it is within the range of general use in the preparation.

  The antioxidant is not particularly limited as long as it can be used for foods, medicines and the like, and examples thereof include tocopherol, ascorbic acid, cysteine hydrochloride, L-ascorbic acid stearate and the like. Of these, ascorbic acid is preferable. The content of the antioxidant in the case where the granulated powder or granule of the present invention contains an antioxidant is not particularly limited as long as it is within the range of general use in the preparation.

  The colorant is not particularly limited as long as it can be used for foods and medicines, and examples thereof include food yellow No. 5, food red No. 2, food blue No. 2, carotenoid pigment, tomato pigment and the like. Of these, carotenoid pigments are preferred. The content of the colorant in the case where the granulated powder or granule of the present invention contains a colorant is not particularly limited as long as it is within the range of general use in the preparation.

  The fragrance is not particularly limited as long as it can be used in foods and medicines, and examples thereof include lemon flavor, lemon lime flavor, grapefruit flavor, and apple flavor. Among these, lemon flavor is preferable. Content of the fragrance | flavor in case the granulated powder or granule of this invention contains a fragrance | flavor should just be in the range of the quantity of the general use in a formulation, and is not specifically limited.

The disintegrant is not particularly limited as long as it can be used in foods, medicines, and the like, and examples thereof include corn starch and potato starch. Of these, corn starch is preferable. The content of the disintegrant in the case where the granulated powder or granule of the present invention contains a disintegrant is not particularly limited as long as it is within the range of general use in the preparation.
Other additives can be used alone or in combination of two or more.

(II) Method for Producing Granulated Powder or Granule The method for producing granulated powder or granule according to the present invention is the method for producing granulated powder or granule according to the present invention described above, and includes (a) glucosamine and (b) calcium phosphate. , Mixing at least one lubricant selected from the group consisting of finely divided silicon dioxide, calcium stearate, and magnesium stearate, and granulating the resulting mixture.

  In the present invention, the method of mixing (a) glucosamine and (b) lubricant is not particularly limited, for example, horizontal cylinder type, inclined cylinder type, V type, double cone type, or raw cube type rotation A mold mixer may be used, and a fixed mixer such as a ribbon mixer, a screw mixer, a rotating disk mixer, or a fluidized mixer may be used. In addition, when (a) glucosamine and (b) lubricant are mixed, after mixing or at the time of granulation, other additives, for example, the above-mentioned sugars, sweeteners, acidulants, binding agents An agent, an antioxidant, a colorant, a fragrance, a disintegrant, etc. may be added and granulated together.

The granulation method is not particularly limited, but for example, the fluidized bed granulation method is preferable. Moreover, a wet granulation method is preferable. Among these, a wet granulation method in which (a) glucosamine or a salt thereof and (b) a lubricant are charged into a fluidized bed granulator and granulated with water or a binder solution is more preferable. Further, the concentration of the binder in the binder solution is generally preferably about 0.1 to 10% by mass, and more preferably about 0.3 to 1% by mass. The binders exemplified above can also be used as binders used in wet granulation.
Further, at the time of granulation, for example, granulation may be performed while spraying an aqueous solution of saccharide having a concentration of about 0.01 to 40% by mass. Examples of the saccharide include pullulan, starch and dextrin in addition to the saccharides exemplified above. Polysaccharides such as starch degradation products, carrageenan, agar, alginic acid, guar gum, chitosan and xanthan gum can also be used. Among these, pullulan, starch and guar gum are preferable, and pullulan is more preferable. About 0.05-3 mass% is preferable with respect to the total mass of the composition used for granulation, and the total spray amount of saccharides has more preferable about 0.1-2 mass%.

  Hereinafter, the present invention will be described in more detail based on examples, but the present invention is not limited to these examples.

  Fermentation glucosamine K (manufactured by Kyowa Hakko Bio) 3940g and calcium phosphate (tricalcium phosphate (manufactured by Taihei Chemical Industrial Co., Ltd.)) 40g are mixed, using a fluidized bed granulator (FLO-5 type, Freund industry) 400 g of a 5% by mass aqueous solution of pullulan (20 g as pullulan (Hayashibara)) was sprayed and granulated to obtain granules. The yield of granules passing through No. 16 sieve (1000 μm) was 97%.

[Comparative Example 1]
3980g of fermented glucosamine K (manufactured by Kyowa Hakko Bio) was sprayed with 400g of 5% by weight pullulan aqueous solution (20g as pullulan (manufactured by Hayashibara)) using a fluidized bed granulator (FLO-5 type, Freund Industries). To obtain granules. The yield of granules passing through No. 16 sieve (1000 μm) was 87.5%.

  In Example 1, glucosamine was granulated satisfactorily and the yield was good, while in Comparative Example 1, many cans were observed and many coarse particles were generated, resulting in a poor yield. The granules obtained in Comparative Example 1 had poor fluidity.

  Fermentation glucosamine K (manufactured by Kyowa Hakko Bio) 80 kg and calcium phosphate 0.8 kg are mixed, then passed through a No. 16 sieve (1000 μm) and put into a fluidized bed granulator (FLO-120, Freund Industries). Granules were obtained by spraying 15 kg of mass% pullulan solution (750 g as pullulan (Hayashibara)). The yield of granules passing through No. 16 sieve (1000 μm) was 97.2%. Further, the fluidity of the obtained granules was good.

  81.4 parts of the glucosamine granules obtained in Example 2 were mixed with 13.6 parts of Theolas FD101 (Asahi Kasei Chemicals) and 5 parts of DK ester F-20W (Daiichi Kogyo Seiyaku) and used with a tableting machine (LIBLA2, Kikusui Seisakusho). φ9mm, 350mg tablets were obtained. Tablet hardness was 90N. It was shown that the flowability of the powder for tableting is good and can be produced in industrial production.

  Since the granulated powder or granule of the present invention has a high content ratio of glucosamine and is sufficiently fluid in practical use, a tablet having a high content of glucosamine can be produced without causing tableting troubles. Therefore, it is extremely superior in industry.

Claims (6)

  A granulated powder or granule containing (a) glucosamine or a salt thereof, and (b) at least one lubricant selected from the group consisting of calcium phosphate, fine silicon dioxide, calcium stearate, and magnesium stearate.   The granulated powder or granule according to claim 1, wherein the lubricant is calcium phosphate.   The granulated powder or granule according to claim 1 or 2, wherein the content of glucosamine or a salt thereof is 90 to 99.9% by mass as glucosamine with respect to the total mass of the granulated powder or granule.   The granulated powder or granule according to any one of claims 1 to 3, wherein the glucosamine or a salt thereof is glucosamine or a salt thereof whose primary particles have a volume average particle diameter of 3 to 200 µm.   The granulated powder or granule according to any one of claims 1 to 4, wherein the content of (b) the lubricant is 0.1 to 10% by mass relative to the total mass of the granulated powder or granule.   (a) mixing glucosamine or a salt thereof with (b) at least one lubricant selected from the group consisting of calcium phosphate, fine silicon dioxide, calcium stearate, and magnesium stearate, and the resulting mixture. The manufacturing method of the granulated powder or granule in any one of Claims 1-5 including the process of granulating.