JP2008127350A - Deodorizing solid composition - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a deodorizing solid composition which can be produced by a simple production method. <P>SOLUTION: This solid composition obtained by wet-granulating a composition comprising a deodorizing ingredient and an odorless swelling agent with water or a water-containing alcohol. The odorless swelling agent is selected from low substituted hydroxypropyl cellulose, crystal cellulose, croscarmellose sodium, crospovidone, carboxymethyl cellulose calcium, carboxymethyl cellulose sodium and carboxymethyl cellulose. <P>COPYRIGHT: (C)2008,JPO&INPIT

Description

  The present invention relates to a solid composition containing a component having an odor and preventing the generation of an odor.

  If an ingredient that generates odor is contained in a solid composition such as pharmaceuticals and foods, it may cause an unpleasant sensation during or after ingestion or the throat of the solid composition may be bad, making it difficult to take In addition, odors may be newly generated or strengthened during storage, and the quality at the time of manufacture may not be maintained for a long time. I had to do it.

Therefore, in order to prevent an unpleasant odor due to a component having an odor in a solid composition, a method of applying a coating such as a sugar coating or a film to a solid preparation such as a granule or a tablet has been attempted, for example, a sugar coating based on sucrose. , Coated with two layers of oil and fat layer and protein layer (Patent Document 2), coating layer of aminoalkyl methacrylate copolymer RS and only hydrophobic substance and water-insoluble inorganic substance A coating layer comprising two coating layers (Patent Document 3), a film coating method containing pullulan and a surfactant (Patent Document 4), a method of coating amino acid particles (Patent Document 5), water-soluble A method of coating with a coating containing a cellulose derivative (Patent Document 6), using a polymer base such as an enteric coating base A method of coating (Patent Document 7), a method of coating a mixture of cyclosporine and sucrose fatty acid ester with a polymer compound (Patent Document 8), and the like are performed. Moreover, as a method of containing a deodorizing or deodorizing component together, a method of containing a chlorine-based oxidizing agent or a peroxide-based oxidizing agent (Patent Document 9), cedar family, cypress family, pine family, birch family, nettle family, A method of adding an extract of a plant tissue of camphoraceae, beech, citrus, persimmonaceae, cucurbitaceae, asteraceae, gramineae, and lilyaceae (Patent Document 10), a method of adding sucralose (patent Document 11), method of adding trehalose to silk peptide and cocoon enzyme degradation product (Patent Document 12), method of adding cyclodextrin and / or cyclodextrin derivative in addition to sulfites (Patent Document 13), heated palatinose (Patent Document 14), adding sulfites (Patent Document 15), adding carboxymethylcellulose or a salt thereof It tried and a method (Patent Document 16), also been carried out a method of encapsulating both solid deodorant (Patent Document 17).
JP-A 61-257923 JP-A-6-24963 JP-A-6-256170 JP 2002-12541 A JP 2003-221326 A WO2005 / 000358 publication JP-A-2005-41818 JP 2005-289825 A JP-A-6-157260 Japanese Patent Laid-Open No. 9-275934 WO00 / 24273 Publication JP 2002-187900 A JP 2003-12439 A Japanese Patent Application Laid-Open No. 2004-2241 JP 2004-331524 A JP 2005-162619 A JP 2004-315046 A

  However, the method of applying a coating such as a sugar coating or a film or the method of encapsulating a deodorant together has a problem that the manufacturing process becomes complicated and the product cost increases, and the deodorizing effect over time is insufficient. There was a case. In addition, the method of adding a deodorant or deodorant component often exhibits effectiveness against a component having a specific unpleasant odor, and the effect is reduced by half if the type of the component having a odor is different. In many cases, it is not a versatile deodorizing method, and the deodorizing or deodorizing component itself may be uncomfortable. Furthermore, since the individual preference is greatly affected by the unpleasant odor, it is preferable that there is no odor of any kind of odors for preparations taken every day such as pharmaceuticals and health foods.

  Accordingly, an object of the present invention is to provide a solid composition capable of preventing odors caused by components having an odor more easily than conventional techniques, and a method for producing the same, by using a substance that is odorless in itself. It is to provide.

  As a result of various investigations on methods for preventing odor from a solid composition containing an odorous component, the present inventors have included an odorous component and an odorless swelling agent, and wet granulation with water or hydrous alcohol The present invention was completed by finding that the solid composition was able to suppress odor unexpectedly.

  That is, the present invention is a solid composition obtained by wet granulation with water or hydrous alcohol, containing a component having odor and an odorless swelling agent.

  The solid composition of the present invention can easily prevent an unpleasant odor caused by a component having an odor by using a substance in which the component itself for preventing the odor is odorless.

Hereinafter, the present invention will be described in detail.
In the present invention, the odorous component is not particularly limited as long as the component itself has a odor, or a part of the component and / or a decomposition product has a odor, and is generally oral. It refers to pharmaceutical raw materials and food raw materials having ingested odors, and may be natural products such as herbal extracts and herbal extracts and extracts thereof as well as chemically synthesized products and fermented products. More specifically, examples of odorous ingredients include Chinese medicines such as Kakkonto, Kaifu Detoyu, Hibikifufumaru, Koshisaifu, Shoseiryu, Suijinto, Tomisen Tokuyu, etc. Extract, aloe, fennel, turmeric, yak, gadget, valerian, citrus, licorice, chrysanthemum, keihi, peonies, shrimp, taiso, butterfly, passiflora, hops, garlic, carrots, ground dragons , Antiulcer drugs such as methylmethioninesulfonium chloride, vitamins such as thiamine, thiamine nitrate, thiamine hydrochloride, bisbenchamine, fursultiamine, octothiamine, benfotiamine, dibenzoylthiamine, thiamine disulfide, bisibthiamine, dicetiamine hydrochloride Group B1, amino acids such as isoleucine, leucine, valine, Eve Antipyretic analgesics such as lofen, mucopolysaccharides such as glucosamine, hyaluronic acid, dermatan sulfate, chondroitin sulfate, vitamin C group such as ascorbic acid or its salt, erythorbic acid or its salt, dl-α-tocopherol, natural vitamin E ( d-form), tocopherol acetate, tocopherol succinate, tocopherol calcium succinate, vitamin E group such as tocopherol nicotinate and the like. Of these, Kakkon-to, ginseng and other herbal medicines and biological extracts, thiamine nitrate, leucine, and tocopherol succinate are preferred.

  In the solid composition of the present invention, the component having an odor is preferably contained in an amount of 1 to 95% by mass, more preferably 2 to 90% by mass, and particularly preferably 5 to 65% by mass.

  In the present invention, the odorless swelling agent is a substance that swells when water or water-containing alcohol is added and can retain a large amount of water or water-containing alcohol, and the substance itself does not have a smell. There is no particular limitation. Examples of more specific odorless swelling agents include low-substituted hydroxypropylcellulose, crystalline cellulose, croscarmellose sodium, crospovidone, carboxymethylcellulose calcium, carboxymethylcellulose sodium, carboxymethylcellulose, and the like. May be used alone or in combination of two or more. Preferred odorless swelling agents include one or more selected from low-substituted hydroxypropylcellulose, carboxymethylcellulose calcium, carboxymethylcellulose sodium, croscarmellose sodium, and crystalline cellulose. More preferred odorless swelling agents include low-substituted hydroxypropyl cellulose, which is desirably used in an amount of 40% by mass or more, particularly preferably 60% by mass or more based on the entire swelling agent.

  When low-substituted hydroxypropylcellulose is used as the odorless swelling agent, the hydroxypropoxy group is 5.0 to 16.5 in terms of manufacturability that it is easy to process into a solid composition having a more excellent deodorizing effect and physical properties. The content is preferably 0% by mass, more preferably 6.0 to 14.5% by mass, and particularly preferably 7.0 to 13.0% by mass. Examples of such low-substituted hydroxypropylcellulose include LH-31 (hydroxypropoxy group 10.0 to 12.9% by mass) and LH-32 (hydroxypropoxy group 7.0 to 9.9) manufactured by Shin-Etsu Chemical Co., Ltd. 9% by mass). Furthermore, the average particle size of the low-substituted hydroxypropylcellulose is preferably 60 μm or less, more preferably 45 μm or less, further preferably 25 μm or less, and particularly preferably 4 to 25 μm.

In the solid composition of the present invention, the odorless swelling agent is preferably contained in an amount of 5 to 99% by mass, more preferably 10 to 98% by mass, and particularly preferably 35 to 95% by mass.
Moreover, the mass ratio of the odorous component and the odorless swelling agent is 0.1 to 100 parts by mass of the odorless swelling agent with respect to 1 part by mass of the odorous component from the viewpoint of an unpleasant odor prevention effect. It is preferably 0.2 to 90 parts by mass, particularly 0.5 to 80 parts by mass.

  In the solid composition of the present invention, other pharmacologically active components and components usually used in pharmaceuticals and foods may be appropriately blended depending on the purpose in addition to the odorous component and the odorless swelling agent. . For example, pharmacologically active ingredients include antipyretic analgesics, antihypnotics, sedatives, drowsiness preventives, antipruritics, pediatric analgesics, stomachic drugs, antacids, digestives, cardiotonic drugs, arrhythmic drugs, antihypertensive drugs, vasodilators Examples include pharmacologically active ingredients used for drugs, diuretics, anti-ulcer drugs, intestinal drugs, osteoporosis drugs, antitussive expectorants, anti-asthma drugs, antibacterial agents, frequent urination improvers, nourishing tonics, vitamins and the like. In addition, examples of components used in pharmaceuticals and foods include excipients (diluents), binders, disintegrants, sweeteners, and coloring agents. Examples of excipients include sugars such as lactose, purified sucrose, glucose and trehalose, and sugar alcohols such as D-mannitol, sorbitol, xylitol and erythritol. Examples of the binder include hydroxypropyl cellulose, hypromellose, methyl cellulose, polyvinyl pyrrolidone, dextrin, pregelatinized starch and the like. Examples of the disintegrant include starches such as corn starch, potato starch, rice starch, and wheat starch. Examples of the sweetener include saccharin sodium, aspartame, acesulfame potassium, sucralose, licorice extract, stevia extract and lacanka extract. Examples of the colorant include titanium dioxide, natural food colors, foodstuffs, and dyes suitable for use in medicine.

  An odor with good palatability can be added to the solid composition of the present invention using a flavoring agent or a fragrance. In that case, a wet granular composition is prepared by wet granulation of a odorous component and an odorless swelling agent with water or a hydrous alcohol, and a solid composition obtained by drying is added to a flavoring agent / fragrance. It is preferable to adopt a method of adding the above. Examples of flavoring agents / fragrances include citrus flavors such as orange and lemon, coffee flavors, milk flavors, plant essential oils such as peppermint oil, spearmint oil, and spice oil.

  The solid composition of the present invention exhibits an effect of suppressing odor by adding a kneading liquid to a composition containing an odorous component and an odorless swelling agent, kneading, and wet granulation. The In the case where a composition in which an odorous component and an odorless swelling agent are simply mixed, or an odorous component and an odorless swelling agent are dry-granulated, a sufficient effect of suppressing the odor cannot be obtained. As a kneading liquid used here, it is preferable to use water or a hydrous alcohol of 50% by mass or less, more preferably water or a hydrous alcohol of 25% by mass or less, and water or a hydrous alcohol of 15% by mass or less. Even more preferably, is used. The alcohol in the hydrous alcohol used in the present invention includes pharmaceuticals such as ethyl alcohol, methyl alcohol, isopropyl alcohol, and alcohols that can be used in the production thereof. Ethyl alcohol should be used for oral administration. Is preferred. The addition amount of the kneading liquid is preferably 1 to 10 times by mass and particularly preferably 2 to 5 times by mass with respect to the odorless swelling agent.

  As the wet granulation when producing the solid composition of the present invention, if it is a wet granulation method usually used in the field of pharmaceuticals and foods such as stirring granulation, fluidized bed granulation, extrusion granulation, etc. Although not particularly limited, a stirring granulation method and an extrusion granulation method are preferable.

  The solid composition of the present invention can be produced, for example, as follows. First, an unpleasant odor component, an odorless swelling agent, and other additives as necessary are added and mixed with a mixer such as a stirrer mixer such as a vertical granulator (manufactured by POWREC). Then, purified water or 50% by weight or less of hydrous alcohol is gradually added to 1 to 10 times the odorless swelling agent and kneaded to bring the odorless swelling agent into a swollen state. The kneaded product is granulated by an extrusion granulator, for example, a fine rewether (Fuji Powder Co., Ltd.) extrusion granulator, to produce a wet granular composition, and a box dryer or fluidized bed granulation Dry in a dryer. It can also be made into granules of the desired particle size using a sieve, and after extruding and granulating with a marumerizer (Fuji Paudal Co., Ltd.), a box dryer or fluidized It is also possible to produce spherical granules of the desired particle size by drying with a layer dryer and finally using a sieve.

  Further, the kneaded product can be immediately dried with a box-type dryer or a fluidized bed granulating dryer, and finally granulated with a desired particle size using a sieve. The particle size of the granules can be adjusted by adjusting the amount of water or hydrous alcohol, or by changing the screen diameter during extrusion granulation in the range of 0.3 to 1.2 mm to obtain powders, fine granules and granules. it can. The obtained granules may be further coated with saccharides, polymers, etc. in consideration of the ingestion and drug stability.

  In the present invention, the average particle size of the granule obtained by wet granulation is preferably 25 μm or more, more preferably 50 to 1500 μm, and more preferably 100 to 1000 μm, when the particle size is measured by a sieving method. Further preferred.

  The solid composition thus produced has a granular shape, the generation of odor due to the odorous component is suppressed, and the fluidity is good. Although it can be used as a fine granule, a granule, etc., it may be filled into a hard capsule or a soft capsule and used as a capsule, or a solid composition granule may be tableted and used as a tablet. Furthermore, these capsules and tablets may be coated with saccharides or polymers. In preparing these preparations, preparation additives usually used in pharmaceuticals and foods are added as stabilizers, stabilizers, surfactants, plasticizers, lubricants, lubricants, reducing agents, sweeteners. , Diluents, adsorbents, flavoring agents, binders, antioxidants, brighteners, coating agents, fragrances, skins, fillers, antifoaming agents, cooling agents, chewing agents, coloring agents, flavoring agents, Dragees, foaming agents, excipients, disintegrating agents, disintegrating aids, disintegrating extenders, fragrances, moisture-proofing agents, preservatives, preservatives, fluidizing agents, antistatic agents, bulking agents, seasonings, acidulants, For sweeteners, colorants / coloring agents, flavoring agents, fortifiers, swelling agents, preservatives, preservatives / antifungal agents, antioxidants / bleaching agents, thickening stabilizers, bittering agents, enzymes, brighteners, for production You may mix | blend timely as an agent. In addition, the solid composition of the present invention and the preparation containing the same produced in this way are prevented from generating odors, and even when filled in an airtight container such as a glass bottle or PTP packaging, the odors develop over time. There is no occurrence.

Next, although an Example and a comparative example are given and this invention is demonstrated further more concretely, this invention is not limited to these.

Example 1
Vertically, 50 g of thiamine nitrate (BASF Japan Co., Ltd.) as an unpleasant odor component and 850 g of low-substituted hydroxypropylcellulose (LHPC: LH-31: Shin-Etsu Chemical Co., Ltd.) as an odorless swelling agent After mixing with granulator VG-10 (Paurec Co., Ltd.), after adding 2620 g of purified water and kneading, it is extruded and granulated with a twin dome gran TDG-80 (Fuji Paudal Co., Ltd.) 0.6 mm screen. Then, it was dried using a fluidized bed drying apparatus FLO-5A / 2 (manufactured by Freund Sangyo Co., Ltd.) to obtain granules having an average particle size of about 500 μm. As a result of 10 g of this granule placed in a glass No. 5 standard bottle, sealed and sealed to test the odor, no unpleasant odor was observed immediately after production and after storage at 40 ° C. for 6 months.

Comparative Example 1
5 g of thiamine nitrate (manufactured by BASF Japan Ltd.) and 85 g of low-substituted hydroxypropylcellulose (LHPC: LH-31: Shin-Etsu Chemical Co., Ltd.) were mixed. As a result of 10 g of this mixture being put in a glass No. 5 standard bottle, sealed and sealed, the unpleasant vitamin odor peculiar to thiamine was observed immediately after production and after storage at 40 ° C. for 6 months.

Example 2
Vertical granulator 200 g of leucine (Ajinomoto Co., Inc.) as an unpleasant odor component and 800 g of low-substituted hydroxypropylcellulose (LHPC: LH-32: Shin-Etsu Chemical Co., Ltd.) as an odorless swelling agent After mixing with VG-10 (Paurec Co., Ltd.), 2094 g of 15% ethanol / purified water was added and kneaded, then extruded with a twin dome gran TDG-80 (Fuji Paudal Co., Ltd.) 0.6 mm screen. After granulation, the mixture was dried with a fluidized bed drying apparatus FLO-5A / 2 (manufactured by Freund Sangyo Co., Ltd.) to obtain granules having an average particle diameter of about 500 μm. As a result of 10 g of this granule placed in a glass No. 5 standard bottle, sealed and sealed to test the odor, no unpleasant odor was observed immediately after production and after storage at 40 ° C. for 6 months.

Comparative Example 2
20 g of leucine (manufactured by Ajinomoto Co., Inc.) and 80 g of low-substituted hydroxypropyl cellulose (LHPC: LH-32: manufactured by Shin-Etsu Chemical Co., Ltd.) were mixed. As a result of 10 g of this mixture being put into a glass No. 5 standard bottle, sealed and sealed, the smell was tested. As a result, an unpleasant odor peculiar to amino acids was observed immediately after production and after storage at 40 ° C. for 6 months.

Example 3
100 g of d-α-tocopherol succinate (manufactured by Eisai Co., Ltd.) as an unpleasant odor component, and low-substituted hydroxypropylcellulose (LHPC: LH-31: manufactured by Shin-Etsu Chemical Co., Ltd.) as an odorless swelling agent ) After mixing 900 g with Vertical Granulator VG-10 (Paurec Co., Ltd.), adding 1902 g of purified water and kneading, Twin Dome Gran TDG-80 (Fuji Paudal Co., Ltd.) 0.6 mm screen After extrusion granulation, it was dried with a fluidized bed drying apparatus FLO-5A / 2 (manufactured by Freund Sangyo Co., Ltd.) to obtain granules having an average particle size of about 500 μm. As a result of 10 g of this granule placed in a glass No. 5 standard bottle, sealed and sealed to test the odor, no unpleasant odor was observed immediately after production and after storage at 40 ° C. for 6 months.

Comparative Example 3
10 g of d-α-tocopherol succinate (manufactured by Eisai Co., Ltd.) and 90 g of low-substituted hydroxypropylcellulose (LHPC: LH-31: Shin-Etsu Chemical Co., Ltd.) were mixed. 10 g of this mixture was put in a glass No. 5 standard bottle, sealed, and tested for odor. As a result, a characteristic unpleasant odor was observed immediately after production and after storage at 40 ° C. for 6 months.

Example 4
149.8 g of Ninjin dried extract (manufactured by Nippon Powder Chemical Co., Ltd.) as an ingredient having an unpleasant odor (1000 g as a raw drug carrot) and low-substituted hydroxypropylcellulose (LHPC: LH-32) as an odorless swelling agent : 280 g manufactured by Shin-Etsu Chemical Co., Ltd.) and 50.2 g of carboxymethylcellulose calcium (Gotoku Pharmaceutical Co., Ltd.) are mixed with a vertical granulator VG-10 (Paurec Co., Ltd.), and then 952 g of purified water is added and kneaded. After being extruded and granulated with a twin dome gran TDG-80 (Fuji Paudal Co., Ltd.) 0.6 mm screen, it is dried with a fluidized bed drying apparatus FLO-5A / 2 (Freund Sangyo Co., Ltd.), Granules having an average particle size of about 500 μm were obtained. As a result of 10 g of this granule placed in a glass No. 5 standard bottle, sealed and sealed to test the odor, no unpleasant odor was observed immediately after production and after storage at 40 ° C. for 6 months.

Comparative Example 4
Ninjin dry extract (Nippon Powder Chemical Co., Ltd.) 7.49g, low substituted hydroxypropylcellulose (LHPC: LH-32: Shin-Etsu Chemical Co., Ltd.) 14g, and carboxymethylcellulose calcium (Gotoku Pharmaceutical Co., Ltd.) )) 2.51 g was mixed. 10 g of this mixture was put in a glass No. 5 standard bottle, sealed, and tested for odor. As a result, a characteristic unpleasant odor was observed immediately after production and after storage at 40 ° C. for 6 months.

Example 5
As an ingredient having an unpleasant odor, 400 g (Nippon Powder Chemical Co., Ltd.) dried extract (2000 g as an active pharmaceutical ingredient) and low-substituted hydroxypropylmethylcellulose (LHPC: LH-31: Shin-Etsu Chemical) as an odorless swelling agent 140 g) and carboxymethyl cellulose calcium (Gotoku Pharmaceutical Co., Ltd.) 210 g were mixed with a vertical granulator VG-10 (Paurec Co., Ltd.), and then 973 g of purified water was added and kneaded. Twin Dome Gran TDG-80 (Fuji Paudal Co., Ltd.) 0.6mm screen extruded and granulated, then dried with fluid bed dryer FLO-5A / 2 (Freund Sangyo Co., Ltd.), average particle size About 500 μm granules were obtained. As a result of 10 g of this granule placed in a glass No. 5 standard bottle, sealed and sealed to test the odor, no unpleasant odor was observed immediately after production and after storage at 40 ° C. for 6 months.

Comparative Example 5
Kakkonto dry extract (Nippon Powder Chemical Co., Ltd.) 20 g, low-substituted hydroxypropylmethylcellulose (LHPC: LH-31: manufactured by Shin-Etsu Chemical Co., Ltd.) 7 g, and carboxymethylcellulose calcium (Gotoku Pharmaceutical Co., Ltd.) 10 0.5 g was mixed. 10 g of this mixture was put in a glass No. 5 standard bottle, sealed, and tested for odor. As a result, a characteristic unpleasant odor was observed immediately after production and after storage at 40 ° C. for 6 months.

  The solid composition of the present invention obtained by wet granulation containing an odorous component and an odorless swelling agent can easily and effectively prevent unpleasant odor caused by the odorous component. Moreover, since the solid composition of the present invention has a granular shape and good fluidity, not only can the granules of the solid composition be used as powders, fine granules, granules, etc. It can be easily processed as a capsule or tablet and can be widely applied to pharmaceuticals, foods, and the like. Furthermore, even if the solid composition of the present invention is stored in an airtight container for a long time, no unpleasant odor is observed, and a stable quality is maintained for a long time. Therefore, the solid composition of the present invention is not only odorless and easy to take, but also a formulation that many consumers with various tastes can take without getting bored over a long period of time.

Claims (4)

  A solid composition containing an odorous component and an odorless swelling agent and obtained by wet granulation with water or a hydrous alcohol.   The solid composition of Claim 1 which contains 0.1-100 mass parts of odorless swelling agents with respect to 1 mass part of components which have an odor.   The odorless swelling agent is one or more selected from low-substituted hydroxypropylcellulose, crystalline cellulose, croscarmellose sodium, crospovidone, carboxymethylcellulose calcium, carboxymethylcellulose sodium and carboxymethylcellulose. 2. The solid composition according to 2.   The solid composition according to claim 1, 2 or 3, wherein the granule obtained by wet granulation has an average particle size of 25 µm or more.