JP2007238486A - Method for producing tablet containing glucosamine, glucosamine-containing tablet and glucosamine-containing granule - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a method for producing tablets containing glucosamines, having good flowability, suitable tablet-forming hardness and a high content of glucosamines, glucosamine-containing tablets obtained from the above method and glucosamine-containing granules excellent in flowability and shape-maintaining property. <P>SOLUTION: The tablets containing glucosamines are obtained by granulation-processing a mixture of glucosamines containing glucosamine and/or its salts and N-acetylglucosamine to form granules, and then tablet-forming the granules. The above mixture of the glucosamines preferably has (8:2) to (2:8) mass ratio of the glucosamine and/or its salts to N-acetylglucosamine by (the glucosamine and/or its salts):(N-acetylglucosamine). <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention relates to a method for producing a glucosamine-containing tablet having a high content of glucosamines and improved tableting properties, a glucosamine-containing tablet obtained by the method, and a glucosamine-containing granule obtained as an intermediate by the method About.

  Glucosamine is 2-aminoglucose in which the hydroxyl group at the 2-position of glucose is substituted with an amino group, and is a typical natural substance widely distributed in important biological components such as glycoproteins, glycolipids and mucopolysaccharides. It is an amino sugar. Industrially, it can be obtained by hydrolyzing chitin contained in crustaceans such as crabs, shrimps and krill, squid cartilage, etc. with acid or enzyme, and separating and purifying. In recent years, not only the importance of glucosamine as a basic constituent molecule of biological components, but also the effectiveness of its intake has been confirmed, and there are many supplements aimed at the effects of treatment and prevention of osteoarthritis, beauty, etc. Have been around.

  There are various types of supplements, but tablets are the most commonly used because they are excellent in storage and portability and can be taken easily regardless of time and place. Is one of the things

  However, glucosamine crystals have physical properties that make it difficult to obtain hardness even after tableting, and tablets with low hardness also have low shape stability, resulting in damage in the distribution process and reduced commercial value. End up. In addition, even in the case of a tablet having a certain hardness, it is necessary to increase the tableting pressure at the time of tableting, which increases the load on the tableting machine and the like. Therefore, glucosamine could not be said to have good tabletability.

  With regard to such problems, for example, in Patent Document 1 below, the fluidity of the raw material powder is improved, the filling into the tablet machine is smooth, the powder is easily compression-molded, and the sticking phenomenon In the production of tablets containing glucosamine that are less likely to occur, direct compression of raw material powder mixture containing (A) hardened oil and fat, (B) collagen and (C) glucosamine and / or isoflavone at room temperature Molding is disclosed.

  In addition, as a technique for solving the tabletability problem of the raw material powder and improving the quality of the tablet, for example, a food additive such as sucrose fatty acid ester which is a lubricant is added to Patent Document 2 below. For the purpose of providing a tablet having a certain hardness and uniformity, a tablet containing saccharides, sugar alcohol, dextrin, starches, gelatin, edible fiber, etc. as excipients and a method for producing the same are disclosed. .

  Generally, the above problem may be improved by compression molding after granulating raw material powder. For example, Patent Document 3 listed below includes a modified whey protein, oligosaccharide as a base material. In addition, a tablet-like or granulated product containing dextrin, starch, etc. as a binder, excellent in tableting properties and granulating properties, having high shape retention and strength, and a method for producing the same are disclosed. Patent Document 4 below discloses a method for producing glucosamine granules, which is granulated after or while spraying a solution containing saccharides other than glucosamine and / or salts thereof on glucosamine and / or salts thereof, and A method for producing a glucosamine tablet obtained by compression molding the glucosamine granule is disclosed.

On the other hand, in Patent Document 5 below, as a method for granulating chitosan which is a multimer of glucosamine, a sugar such as dextrin is mixed as a sub-base material for a binder and then shaken while spraying a liquid such as water or alcohol. Thus, a method for producing water-soluble chitosan-containing granules is disclosed.
Japanese Patent Laid-Open No. 2001-288073 JP 2001-342129 A Japanese Patent No. 3188657 JP 2006-36644 A JP 2000-53704 A

  Since glucosamine crystals have physical properties that are difficult to granulate, sufficient granulation or tableting cannot be performed even with only water or alcohol as a binder. In fact, in any of the above Patent Documents 1 to 5, granulation or tableting is performed using a sub-base material other than glucosamine. Therefore, the glucosamine content of the tablets or granules obtained is limited, and it is necessary to increase the amount of intake in order to sufficiently obtain the physiological function of glucosamine.

  Moreover, in the said patent document 1, the collagen which is a natural polymer composition prepared from a cow bone, a pig skin, a fish bone, etc. is used as an auxiliary base material for tableting. Moreover, in the said patent document 3, a modified whey protein is used as an auxiliary base material for tableting. For this reason, in the said patent documents 1 and 3, it is difficult to prevent mixing of an allergenic substance, and there existed a case where it was not applicable to a wide use.

  On the other hand, N-acetylglucosamine, which is a glucosamine derivative, is expected to have effects such as treatment / prevention of osteoarthritis and beauty, as with glucosamine, and high tablet hardness is obtained when tableting is performed. However, since N-acetylglucosamine is a needle-like crystal, the flowability is very poor, and there is difficulty in uniformly filling the tableting machine. Therefore, it is difficult to ensure the uniformity of tablets obtained by tableting, and even if granulation is performed before tableting, the fluidity is not improved so much.

  Accordingly, an object of the present invention is to avoid the problems associated with the prior art described above, and to provide a method for producing a glucosamine-containing tablet having an appropriate tableting hardness and a high glucosamine content, and the glucosamines obtained by the method. An object of the present invention is to provide a tablet containing glucosamine and a granule containing glucosamine excellent in fluidity and shape maintenance.

  As a result of diligent research to achieve the above object, the present inventors have mixed glucosamine and N-acetylglucosamine, and granulated and / or tableted the mixture to obtain a conventional glucosamine punch. The present inventors have found that glucosamine-containing tablets having high tablet hardness can be obtained by improving the problems related to tablet properties, and have completed the present invention.

  That is, in the method for producing a glucosamine-containing tablet of the present invention, a glucosamine mixture containing glucosamine and / or a salt thereof and N-acetylglucosamine is granulated into granules, and then the granules are compressed into tablets. It is characterized by molding.

  In the method for producing a glucosamine-containing tablet of the present invention, the mass ratio of glucosamine and / or a salt thereof to N-acetylglucosamine is (glucosamine and / or a salt thereof) :( N-acetylglucosamine): ) Is preferably 8: 2 to 2: 8. According to this aspect, the tableting suitability of glucosamines can be sufficiently improved, and furthermore, a glucosamine-containing tablet with high hardness can be obtained.

  Moreover, in the manufacturing method of the glucosamine containing tablet of this invention, it is preferable to spray and granulate the said glucosamine mixture to the solution containing saccharides. According to this aspect, it is possible to obtain a glucosamine-containing tablet having excellent tableting suitability, hardly causing sticking or the like during tableting, and having moderately high hardness after tableting.

  The saccharide preferably contains at least one selected from glucosamine, glucosamine salts and N-acetylglucosamine. According to this aspect, it is possible to obtain a glucosamine-containing tablet having an extremely high content of glucosamines, and further having a moderately high hardness after tableting.

  On the other hand, the glucosamine-containing tablet of the present invention is a tablet obtained by the above production method, and has a hardness of 4 kgf or more.

  In the glucosamine-containing tablet of the present invention, the total content of glucosamine and / or salts thereof and N-acetylglucosamine is preferably 50% by mass or more, and more preferably 90% by mass or more.

  Moreover, the glucosamine containing granule by this invention is a glucosamine containing granule manufactured as an intermediate body in the manufacturing method of the said glucosamine containing tablet, It is characterized by the above-mentioned.

  According to the present invention, a glucosamine-containing tablet having a high glucosamine content, a homogeneous and sufficiently high hardness, and a glucosamine-containing granule excellent in fluidity and shape maintenance can be obtained.

  In the method for producing a glucosamine-containing tablet of the present invention, a glucosamine mixture containing glucosamine and / or a salt thereof and N-acetylglucosamine is granulated to form granules, and then the granules are compressed into tablets. It is characterized by that.

  The glucosamine is not particularly limited in its origin, production method, and the like. For example, chitin contained in crustaceans such as shrimp, crab, krill, squid cartilage, etc. is hydrolyzed with an acid or enzyme, etc., separated, purified, and crystallized. Can be obtained. Moreover, you may use the commercially available glucosamine, for example, brand name "natural glucosamine" (made by Yaizu Suisan Chemical Co., Ltd.) etc. are mentioned. Examples of the glucosamine salts include hydrochloride, sulfate, lactate and the like.

  The origin of the N-acetylglucosamine is not particularly limited, but chitin obtained from crustaceans such as crabs and shrimps is used as a raw material, for example, Japanese Patent Publication No. 5-33037 and Japanese Patent Application Laid-Open No. 2000-281696. It is preferable to use natural N-acetylglucosamine obtained according to the method described in the publication. In other words, N-acetylchitooligosaccharide-containing mixture obtained by partial hydrolysis of polysaccharide chitin prepared from crustacean shells such as crabs and shrimps with acid is capable of hydrolyzing N-acetylchitooligosaccharide. It is preferable to use an enzyme having an enzyme (for example, lysotium, chitinase, chitobiase, etc.), which is decomposed and purified as necessary. Since N-acetylglucosamine obtained as described above is a natural type that has not been chemically synthesized, it can be taken more safely as a food. In addition, the natural type N-acetylglucosamine manufactured as mentioned above is marketed, for example, a brand name "Marine Sweet" (made by Yaizu Suisan Chemical Co., Ltd.) etc. can be used.

  Glucosamine is mixed so that the mass ratio of glucosamine and / or salt thereof to N-acetylglucosamine is (glucosamine and / or salt thereof) :( N-acetylglucosamine) and is 8: 2 to 2: 8. It is preferable to prepare a kind-containing mixture, more preferably 6: 4 to 2: 8, and particularly preferably 4: 6 to 2: 8. If the mass ratio of glucosamine and / or a salt thereof and N-acetylglucosamine is within the above range, the disadvantage of low tablet hardness after tableting that glucosamine crystals have, and the punching that N-acetylglucosamine crystals have. Glucosamine-containing granular materials that compensate for each of the disadvantages of poor fluidity when filling into a tablet machine, have excellent shape maintenance and fluidity, and have high hardness when tableted, even if no excipients are added. Can be obtained. On the other hand, if the mass ratio of glucosamine and / or salts thereof and N-acetylglucosamine is outside the above range, tableting suitability may not be sufficiently improved.

  In the present invention, when preparing a glucosamine-containing mixture, sub-base materials may be mixed and used to the extent that they do not adversely affect physical properties such as tableting suitability, fluidity, and shape maintenance of glucosamines.

  Examples of such auxiliary base materials include starches such as starch and dextrin and degradation products thereof; polysaccharides such as carrageenan, agar, alginic acid, guar gum, chitosan, and xanthan gum; monosaccharides such as sugar, glucose, lactose, and maltose; Normal production of granule preparations other than disaccharides; oligosaccharides such as fructooligosaccharides, maltooligosaccharides, isomaltoligosaccharides, galactooligosaccharides, chitin oligosaccharides and chitosan oligosaccharides; sugar alcohols such as maltitol, sorbitol, xylitol and erythritol Components such as thickeners and emulsifiers used in the above can be used. By appropriately blending these sub-base materials, the productivity during granulation and / or tableting can be increased, and the shape stability of the glucosamine-containing granular product can be further improved, In the present invention, a glucosamine-containing granular product having excellent physical properties such as fluidity and shape maintaining property and having excellent hardness when tableting can be obtained without using the sub-base material. When using the said sub-base material, it is preferable to use so that it may become 20 mass% or less with respect to the whole quantity of a glucosamine containing granular material, and 10 mass% or less is preferable.

  The total content of glucosamine and / or salts thereof and N-acetylglucosamine in the glucosamine-containing mixture is preferably 50% by mass or more, more preferably 70% by mass or more, and 90% by mass. % Or more is even more preferable, and 99% by mass or more is most preferable.

  In the present invention, first, the glucosamine mixture is granulated to obtain glucosamine-containing granules. The granulation processing method of the glucosamine mixture is not particularly limited. For example, in the process of mixing glucosamine and / or a salt thereof with N-acetylglucosamine and forming particles in which the crystals are aggregated, water, ethanol, etc. This binder can be granulated while spraying uniformly on a glucosamine-containing mixture containing glucosamine and / or a salt thereof and N-acetylglucosamine. There are no particular restrictions on the granulator. For example, a fluidized bed granulator, a stirring granulator, an extrusion granulator or the like can be used. Moreover, conditions at the time of granulation such as the intake air temperature in the granulation tank and the temperature of the spray liquid can be set as appropriate, but the intake air temperature is usually preferably 40 to 90 ° C, more preferably 40 to 70 ° C. Moreover, 10-80 degreeC is preferable and the temperature of a spray liquid has more preferable 20-60 degreeC.

  In the present invention, when granulating, a part or all of the saccharide used as the auxiliary base material is dissolved in a solvent such as water or alcohol to form a binder, and the binder is converted into a glucosamine-containing mixture. It is preferable to perform granulation by spraying, and it is particularly preferable to perform granulation by spraying a binder containing at least one saccharide selected from glucosamine, glucosamine salts, and N-acetylglucosamine on the glucosamine-containing mixture. . By spraying the binder containing the saccharide, the glucosamine crystals are coated with the saccharide, and by granulating in that state, the physical properties suitable for tableting processing, that is, excellent fluidity, and after compression molding A glucosamine-containing granule having physical properties capable of obtaining a moderately high hardness can be obtained. And by using at least 1 sort (s) chosen from glucosamine, glucosamine salts, and N-acetylglucosamine as saccharides used for a binder, tableting ability can be improved, without reducing the content of glucosamine.

  The saccharide used for the binder is selected from dextrin, sugar, glucose, lactose, maltose, fructooligosaccharide, maltooligosaccharide, isomaltooligosaccharide, galactooligosaccharide, chitin oligosaccharide, chitosan oligosaccharide, maltitol, sorbitol, xylitol, and erythritol. One type or two or more types can also be used. Moreover, these saccharides can be used in combination with at least one selected from glucosamine, glucosamine salts, and N-acetylglucosamine. More preferably, the saccharide used for the binder is one containing at least one selected from glucosamine, glucosamine salts, and N-acetylglucosamine and dextrin.

  In the case of granulating using a binder containing saccharides, the sugar concentration of the binder is not particularly limited because it varies depending on the saccharide used, but for example, 0.1 to 5 weight if it is a highly viscous polysaccharide % Is preferable, and 0.5 to 2% by weight is more preferable. Moreover, if it is another saccharide, 1-60 weight% is preferable on the assumption that the solubility is not exceeded, and 10-40% is more preferable. When the binder sugar concentration is lower than the above value, the effect of the binder is hardly obtained, and when the binder sugar concentration is higher than the above, the solution becomes too viscous to spray uniformly. This is not preferable because it is difficult to obtain uniform granules in the end.

  Moreover, it is preferable that 5 mass% or more of the said saccharide | sugar contained in a binder is glucosamine, glucosamine salts, and N-acetylglucosamine, and it is more preferable that it is 50 mass% or more.

  The glucosamine granules thus obtained have a total content of glucosamine and / or a salt thereof and N-acetylglucosamine of preferably 90% or more, more preferably 95% or more, and 99% The above is particularly preferable.

  The glucosamine-containing granules of the present invention can be suitably used as an intermediate when producing a glucosamine-containing tablet, because it is excellent in fluidity and shape maintenance while ensuring a sufficient content as glucosamine, It can also be used as a granule itself. For example, when used as a granule itself, it is preferably used in a form filled in a small bag such as a hard capsule or a stick-shaped bag.

  The glucosamine-containing tablet of the present invention can be obtained by tableting the glucosamine-containing granule obtained by granulation as described above. In tableting, a sub-tablet for tableting may be blended within a range that does not greatly affect the physical properties, glucosamine content and the like of the resulting glucosamine-containing tablet. Examples of the auxiliary base material for tableting include crystalline cellulose, dextrin, maltitol, gelatin, natural gums, potato starch, sodium alginate and the like, and excipients usually used for the preparation of tableting formulations Ingredients such as thickeners, emulsifiers and lubricants can be used, and are not particularly limited.

  By appropriately blending these tableting sub-base materials for tableting, the productivity during tableting can be increased, and the shape stability of the glucosamine tablet product can be further improved.

  Furthermore, you may mix | blend active ingredients other than glucosamine in the range which does not impair the hardness of the glucosamines containing tablet obtained. As active ingredients other than glucosamine, for example, arginine, taurine, glutamic acid, histidine, branched chain amino acids (leucine, isoleucine, valine) and the like are used as amino acids. Further, imidazole compounds such as histidine, 1-methylhistidine, 3-methylhistidine, anserine, carnosine, homocarnosine, and valenin can be used in combination. In addition, octacosanol, citric acid, acetic acid, chitin dimer, chitin pentamer, chitosan hexamer, oligoglucosamine, eicosapentaenoic acid, docosapentaenoic acid, docosahexaenoic acid, red pepper, ginseng, zinc-containing yeast, selenium-containing yeast, etc. it can.

Although it does not specifically limit as a tableting shaping | molding method, It can obtain by compressing the said glucosamine containing granule or the said glucosamine containing mixture using a tableting machine. Although there is no restriction | limiting in particular as a tableting machine, For example, a high-speed rotation tablet machine etc. are used. The operating conditions such as tableting pressure vary depending on the shape and size of the tablet to be produced, and are not particularly limited. For example, a tableting machine equipped with a punch having a diameter of 5 to 20 mm and a curvature radius of 6 to 24 mm is used. Glucosamines used, wherein the mass ratio of glucosamine and / or salt thereof to N-acetylglucosamine is (glucosamine and / or salt thereof) :( N-acetylglucosamine) and is 4: 6 to 2: 8 When tableting the contained granule to produce a round tablet of 100 to 2,000 mg / tablet, it is preferable to perform tableting under a tableting pressure of 600 to 2,500 kgf / cm ² , thereby To obtain a glucosamine-containing tablet having a hardness of 4 kgf or more, even if the total content of glucosamine and / or a salt thereof and N-acetylglucosamine is 90% by mass or more Can do.

  The glucosamine-containing tablet of the present invention obtained as described above has a high content of the glucosamines and sufficient hardness. The hardness of the glucosamine-containing tablet needs to be 4 kgf or more, and more preferably 6 to 15 kgf. If the tablet hardness is within the above range, the dosage form does not collapse during transportation, ingestion, etc., and it has sufficient dosage form maintainability and can be used for PTP packaging.

  Moreover, there is no restriction | limiting in particular about the shape of a glucosamine containing tablet, a magnitude | size, etc., For example, all shapes, such as a round shape, an ellipse shape, a triangular shape, a square shape, are mentioned, Diameter 5mm-20mm, Weight 100mg-2,000mg It can be made into a dosage form.

  The total content of glucosamine and / or salts thereof and N-acetylglucosamine in the glucosamine-containing tablets (including granules and tablets) of the present invention is preferably 50% by mass or more, and 70% by mass or more. More preferably, it is more preferably 90% by mass or more, and most preferably 99% by mass or more.

  Hereinafter, the present invention will be described in more detail by way of examples. In Examples 1 and 2 below, as glucosamine, “natural glucosamine” (trade name, manufactured by Yaizu Suisan Chemical Co., Ltd.) is used, and as N-acetylglucosamine, “marine sweet” (trade name, Yaizu Fishery Chemical Industry Co., Ltd.) was used.

Example 1
The granule base materials were mixed with the formulation shown in Table 1 to obtain a glucosamine mixture. Then, using a fluidized granulator (trade name “Flow Coater”; manufactured by Freund Sangyo Co., Ltd.), sprayed at 15 ml / min with a normal temperature spray solution adjusted to the blending ratio shown in Table 1 onto this glucosamine mixture. The granulation process was performed. Thereafter, the obtained granulated product was dried at a temperature of 70 ° C. until the water content became 1% or less to obtain granules containing glucosamines. Then, this glucosamine-containing granule is punched using a tableting machine (trade name “VIRGO”; manufactured by Kikusui Seisakusho Co., Ltd.) equipped with a punch having a diameter of 8 mm and a radius of curvature of 12 mm (8 mm round φ12R) according to a conventional method. Tableting was performed at a tablet pressure of 1,000 kg to obtain 250 mg / tablet glucosamine-containing tablets.

  About the obtained glucosamines containing tablet, hardness was measured according to the JP hardness measurement method using a hardness meter (trade name “FY-KD-20”; manufactured by Fuji Pharmaceutical Co., Ltd.). In addition, the fluidity of the glucosamine-containing granules before tableting was evaluated by measuring the angle of repose using the injection angle method. As a specific measurement method, when each sample was injected into a cylindrical container having an inner diameter of 4.7 cm and a depth of 6 cm from a height of 10 cm through a circular discharge port having an inner diameter of 8 mm, the sample overflowed from the container. The angle of the slope formed on the container was measured on the left and right sides, and the average was taken as the angle of repose. The results are summarized in Table 1.

  The glucosamine-containing tablet of Sample 6 containing only N-acetylglucosamine had poor fluidity during tableting and could not be smoothly filled into the tablet die. In addition, sample 5 containing only glucosamine and sample 6 containing only N-acetylglucosamine both had problems such as binding and capping, and the tableting process was not performed smoothly. The tableting hardness is very low, and it can be easily broken just by holding it by hand.

  On the other hand, the glucosamine-containing tablets of Samples 1 to 4 containing glucosamine and N-acetylglucosamine have high tableting hardness, are not easily disintegrated, and have excellent shape stability. In the processing, the fluidity was good, the tablet was filled into the die smoothly, and the tableting could be performed smoothly without problems such as binding and capping.

(Example 2)
With the formulation shown in Table 2, 250 mg / tablet glucosamine tablets were obtained in the same manner as in Example 1. Further, the hardness of the obtained tablet and the angle of repose of the granule before tableting were also measured by the same method as in Example 1. The results are summarized in Table 2.

  The glucosamine-containing tablets of Samples 7 to 11 all have sufficient tablet hardness, and in particular, the glucosamine-containing tablets of Samples 8 to 11 using a spray solution containing glucosamine and / or N-acetylglucosamine have hardness. In particular, in Sample 11, the glucosamine-containing granule before tableting processing has excellent fluidity, shape maintenance, etc., even though no excipient is used, Moreover, the tablet after the tableting process had sufficient hardness. In any of the samples 7 to 11, the tableting process has good fluidity and can be smoothly filled into the die of the tableting machine, and there is no trouble such as capping. We were able to do it smoothly.

Claims (8)

  A method for producing a glucosamine-containing tablet, comprising granulating a glucosamine mixture containing glucosamine and / or a salt thereof and N-acetylglucosamine to form granules, and then pressing the granules. .   In the glucosamine mixture, the mass ratio of glucosamine and / or salt thereof to N-acetylglucosamine is (glucosamine and / or salt thereof) :( N-acetylglucosamine), and is 8: 2 to 2: 8. The manufacturing method of the glucosamines containing tablet of Claim 1.   The method for producing a glucosamine-containing tablet according to claim 1 or 2, wherein the glucosamine mixture is sprayed with a solution containing a saccharide and granulated.   The method for producing a glucosamine-containing tablet according to claim 3, wherein the saccharide contains at least one selected from glucosamine, glucosamine salts, and N-acetylglucosamine.   A tablet obtained by the production method according to any one of claims 1 to 4, wherein the tablet has a hardness of 4 kgf or more.   The glucosamine-containing tablet according to claim 5, wherein the total content of glucosamine and / or a salt thereof and N-acetylglucosamine is 50% by mass or more.   The glucosamine-containing tablet according to claim 6, wherein the total content of glucosamine and / or a salt thereof and N-acetylglucosamine is 90% by mass or more.   In the manufacturing method of the glucosamine containing tablet as described in any one of Claims 1-4, the glucosamine containing granule manufactured as the intermediate body.