JP6668706B2 - Solid composition - Google Patents
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- JP6668706B2 JP6668706B2 JP2015231570A JP2015231570A JP6668706B2 JP 6668706 B2 JP6668706 B2 JP 6668706B2 JP 2015231570 A JP2015231570 A JP 2015231570A JP 2015231570 A JP2015231570 A JP 2015231570A JP 6668706 B2 JP6668706 B2 JP 6668706B2
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- 239000008247 solid mixture Substances 0.000 title claims description 46
- BLUBRLPOVKKUGF-DJUDWIIFSA-N 3',6-di-O-sinapoylsucrose Natural products COc1cc(C=CC(=O)OC[C@H]2O[C@@](CO)(O[C@H]3O[C@H](CO)[C@@H](O)[C@H](OC(=O)C=Cc4cc(OC)c(O)c(OC)c4)[C@H]3O)[C@@H](O)[C@@H]2O)cc(OC)c1O BLUBRLPOVKKUGF-DJUDWIIFSA-N 0.000 claims description 29
- 150000002148 esters Chemical class 0.000 claims description 29
- 239000000843 powder Substances 0.000 claims description 14
- 239000000203 mixture Substances 0.000 claims description 13
- 229920002472 Starch Polymers 0.000 claims description 9
- 239000003814 drug Substances 0.000 claims description 9
- 239000000845 maltitol Substances 0.000 claims description 9
- VQHSOMBJVWLPSR-WUJBLJFYSA-N maltitol Chemical compound OC[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O VQHSOMBJVWLPSR-WUJBLJFYSA-N 0.000 claims description 9
- 229940035436 maltitol Drugs 0.000 claims description 9
- 235000010449 maltitol Nutrition 0.000 claims description 9
- 239000011734 sodium Substances 0.000 claims description 9
- 229910052708 sodium Inorganic materials 0.000 claims description 9
- 239000008107 starch Substances 0.000 claims description 9
- 235000019698 starch Nutrition 0.000 claims description 9
- 229940079593 drug Drugs 0.000 claims description 7
- 239000008187 granular material Substances 0.000 claims description 6
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 claims description 6
- 239000003826 tablet Substances 0.000 claims description 4
- 239000002775 capsule Substances 0.000 claims description 3
- 239000007910 chewable tablet Substances 0.000 claims description 3
- 239000006191 orally-disintegrating tablet Substances 0.000 claims description 3
- 239000006188 syrup Substances 0.000 claims description 3
- 235000020357 syrup Nutrition 0.000 claims description 3
- 229940068682 chewable tablet Drugs 0.000 claims description 2
- 230000000052 comparative effect Effects 0.000 description 15
- 230000000694 effects Effects 0.000 description 12
- 230000007423 decrease Effects 0.000 description 11
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 10
- BIVBRWYINDPWKA-VLQRKCJKSA-L Glycyrrhizinate dipotassium Chemical compound [K+].[K+].O([C@@H]1[C@@H](O)[C@H](O)[C@H](O[C@@H]1O[C@H]1CC[C@]2(C)[C@H]3C(=O)C=C4[C@@H]5C[C@](C)(CC[C@@]5(CC[C@@]4(C)[C@]3(C)CC[C@H]2C1(C)C)C)C(O)=O)C([O-])=O)[C@@H]1O[C@H](C([O-])=O)[C@@H](O)[C@H](O)[C@H]1O BIVBRWYINDPWKA-VLQRKCJKSA-L 0.000 description 10
- 229940101029 dipotassium glycyrrhizinate Drugs 0.000 description 10
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 9
- 239000000600 sorbitol Substances 0.000 description 9
- 241000234282 Allium Species 0.000 description 8
- 235000002732 Allium cepa var. cepa Nutrition 0.000 description 8
- 241000544066 Stevia Species 0.000 description 8
- HELXLJCILKEWJH-NCGAPWICSA-N rebaudioside A Chemical compound O([C@H]1[C@H](O)[C@@H](CO)O[C@H]([C@@H]1O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)O[C@]12C(=C)C[C@@]3(C1)CC[C@@H]1[C@@](C)(CCC[C@]1([C@@H]3CC2)C)C(=O)O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O HELXLJCILKEWJH-NCGAPWICSA-N 0.000 description 8
- 229940083542 sodium Drugs 0.000 description 8
- FTLYMKDSHNWQKD-UHFFFAOYSA-N (2,4,5-trichlorophenyl)boronic acid Chemical compound OB(O)C1=CC(Cl)=C(Cl)C=C1Cl FTLYMKDSHNWQKD-UHFFFAOYSA-N 0.000 description 4
- 229940085605 saccharin sodium Drugs 0.000 description 4
- 238000009472 formulation Methods 0.000 description 3
- 239000011521 glass Substances 0.000 description 3
- 238000003860 storage Methods 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 230000003925 brain function Effects 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 230000036962 time dependent Effects 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 208000000659 Autoimmune lymphoproliferative syndrome Diseases 0.000 description 1
- 241001080798 Polygala tenuifolia Species 0.000 description 1
- 229920003110 Primojel Polymers 0.000 description 1
- 206010039897 Sedation Diseases 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 235000021329 brown rice Nutrition 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000013583 drug formulation Substances 0.000 description 1
- 239000003172 expectorant agent Substances 0.000 description 1
- 230000003419 expectorant effect Effects 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000007087 memory ability Effects 0.000 description 1
- 230000003340 mental effect Effects 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000004014 plasticizer Substances 0.000 description 1
- 238000010298 pulverizing process Methods 0.000 description 1
- 230000036280 sedation Effects 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000002123 temporal effect Effects 0.000 description 1
- 230000001256 tonic effect Effects 0.000 description 1
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- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Plant Substances (AREA)
Description
本発明は、3’,6-di-O-sinapoyl-sucrose esterを含有する固形組成物に関する。 The present invention relates to a solid composition containing 3 ', 6-di-O-sinapoyl-sucrose ester.
オンジに含まれている3’,6-di-O-sinapoyl-sucrose esterには、脳機能改善効果があることが知られている（特許文献１）。また、オンジにも脳機能改善に関するものとして、記憶力改善等の効果があることが知られている。このような効果を目的として3’,6-di-O-sinapoyl-sucrose esterを含む医薬品等の製品とした場合、如何に3’,6-di-O-sinapoyl-sucrose esterの含量を維持できるかが重要である。特に、オンジを配合した医薬組成物とした場合、生薬中の主成分の低下は医薬品として品質確保の点で問題となるため、解決策が望まれる。 It is known that 3 ', 6-di-O-sinapoyl-sucrose ester contained in onji has a brain function improving effect (Patent Document 1). Also, it is known that onji also has an effect of improving memory ability and the like as related to improvement of brain function. When a product such as a medicine containing 3 ', 6-di-O-sinapoyl-sucrose ester is used for the purpose of such an effect, how can the content of 3', 6-di-O-sinapoyl-sucrose ester be maintained? Is important. In particular, in the case of a pharmaceutical composition containing ondi, a decrease in the main component in the crude drug becomes a problem in terms of ensuring quality as a pharmaceutical, and a solution is desired.
3’,6-di-O-sinapoyl-sucrose esterは、オンジ以外に、玄米中にも含まれる成分であることが知られているが、医薬品等の固形組成物とした際の安定性の問題については検討された例はない。よって、当然のことながら、その解決方法についても全く知られていない。 3 ', 6-di-O-sinapoyl-sucrose ester is known to be a component also contained in brown rice, in addition to onji, but has a problem of stability when used as a solid composition such as pharmaceuticals. There are no examples examined. Thus, of course, no solution is known.
本発明者らは、オンジを含む固形組成物の開発に際し、3’,6-di-O-sinapoyl-sucrose esterの安定性について検討としたところ、経時的に含量が低下するという知見を得た。従って、本発明の課題は、3’,6-di-O-sinapoyl-sucrose esterの安定化された固形組成物の提供である。 The present inventors have studied the stability of 3 ', 6-di-O-sinapoyl-sucrose ester when developing a solid composition containing ondi, and found that the content decreases with time. . Accordingly, an object of the present invention is to provide a stabilized solid composition of 3 ', 6-di-O-sinapoyl-sucrose ester.
本発明者らは、上記課題を解決するべく鋭意検討した結果、カルボキシメチルスターチナトリウム、ソルビトール、ステビア、グリチルリチン酸二カリウム、マルチトール、及びサッカリンナトリウムからなる群から選ばれる少なくとも１種を配合すると、3’,6-di-O-sinapoyl-sucrose esterの経時的な低下が抑制されることを見出し、本発明を完成するに至った。すなわち、本発明は、
（１）3’,6-di-O-sinapoyl-sucrose ester、並びに、カルボキシメチルスターチナトリウム、ソルビトール、ステビア、グリチルリチン酸二カリウム、マルチトール、及びサッカリンナトリウムからなる群から選ばれる少なくとも１種を含有することを特徴とする固形組成物、
（２）オンジを含有する（１）に記載の固形組成物、
（３）オンジが、オンジ末、オンジエキス、又はオンジエキス末である（２）に記載の固形組成物、
（４）固形組成物が内服用である、（１）〜（３）のいずれかに記載の固形組成物、
（５）固形組成物が錠剤、顆粒剤、散剤、カプセル剤、チュアブル錠剤、口腔内崩壊錠又はドライシロップ剤である、（１）〜（４）のいずれかに記載の固形組成物、
（６）3’,6-di-O-sinapoyl-sucrose esterの経時的な含量低下を抑制するために、カルボキシメチルスターチナトリウム、ソルビトール、ステビア、グリチルリチン酸二カリウム、マルチトール、及びサッカリンナトリウムからなる群から選ばれる少なくとも１種を使用する方法、
（７）カルボキシメチルスターチナトリウム、ソルビトール、ステビア、グリチルリチン酸二カリウム、マルチトール、及びサッカリンナトリウムからなる群から選ばれる少なくとも１種を添加することによって、3’,6-di-O-sinapoyl-sucrose esterの経時的な含量低下を抑制する方法、
である。
The present inventors have conducted intensive studies to solve the above problems, and as a result, when at least one selected from the group consisting of sodium carboxymethyl starch, sorbitol, stevia, dipotassium glycyrrhizinate, maltitol, and sodium saccharin, 3 The inventors have found that the time-dependent decrease of ', 6-di-O-sinapoyl-sucrose ester is suppressed, and have completed the present invention. That is, the present invention
(1) It contains 3 ', 6-di-O-sinapoyl-sucrose ester and at least one member selected from the group consisting of sodium carboxymethyl starch, sorbitol, stevia, dipotassium glycyrrhizinate, maltitol and sodium saccharin. A solid composition,
(2) The solid composition according to (1), which contains ondi,
(3) The solid composition according to (2), wherein the ondi is ondi powder, ondi extract, or ondi extract powder,
(4) The solid composition according to any one of (1) to (3), wherein the solid composition is for internal use.
(5) The solid composition according to any one of (1) to (4), wherein the solid composition is a tablet, granule, powder, capsule, chewable tablet, orally disintegrating tablet or dry syrup.
(6) a group consisting of sodium carboxymethyl starch, sorbitol, stevia, dipotassium glycyrrhizinate, maltitol, and sodium saccharin in order to suppress a temporal decrease in the content of 3 ′, 6-di-O-sinapoyl-sucrose ester A method using at least one selected from the group consisting of:
(7) 3 ', 6-di-O-sinapoyl-sucrose ester by adding at least one selected from the group consisting of sodium carboxymethyl starch, sorbitol, stevia, dipotassium glycyrrhizinate, maltitol and sodium saccharin. A method for suppressing a decrease in the content over time of
It is.
本発明により、長期にわたって3’,6-di-O-sinapoyl-sucrose esterの経時的な低下が抑制された固形組成物の提供が可能となった。 According to the present invention, it has become possible to provide a solid composition in which a decrease in 3 ′, 6-di-O-sinapoyl-sucrose ester over time is suppressed.
本発明の3’,6-di-O-sinapoyl-sucrose esterは、オンジに含まれる成分であり、公知である。3’,6-di-O-sinapoyl-sucrose esterの含有量は、本発明の固形組成物中、０．０１〜３質量％が好ましい。また、3’,6-di-O-sinapoyl-sucrose esterは、オンジに含まれる成分であるため、本発明の組成物中にオンジを含む場合は、これとは別に3’,6-di-O-sinapoyl-sucrose esterを配合する必要はないが、配合してもよい。 The 3 ', 6-di-O-sinapoyl-sucrose ester of the present invention is a component contained in ondi and is known. The content of 3 ', 6-di-O-sinapoyl-sucrose ester is preferably 0.01 to 3% by mass in the solid composition of the present invention. In addition, since 3 ', 6-di-O-sinapoyl-sucrose ester is a component contained in an ondi, when the composition of the present invention contains an ondi, 3', 6-di- It is not necessary to mix O-sinapoyl-sucrose ester, but it may be.
本発明のオンジは、去痰、鎮静、滋養強壮、精神安定、記憶力改善等の効果があることが知られた生薬である。本発明のオンジとしては、例えば第１６改正日本薬局方収載のオンジ（ヒメハギ属のイトヒメハギ（Ｐｏｌｙｇａｌａ ｔｅｎｕｉｆｏｌｉａ）の根）の粉砕物であるオンジ末、もしくは水やエタノール等の有機溶媒により抽出した抽出物であるオンジエキス、又はエキスを粉末化したオンジエキス末を使用することができる。市販品としては、例えば、オンジ末（栃本天海堂）、オンジエキス−Ａ（日本粉末薬品）、オンジ乾燥エキス（アルプス薬品工業）等が使用できる。本発明の固形組成物において、オンジの含有量は、固形組成物全体の１０質量％以上が好ましく、３０質量％以上がさらに好ましい。また上限は９０質量％である。また原生薬換算で、本発明の固形組成物中に２５０mg以上、好ましくは３３０mg以上、より好ましくは５００mg以上である。 The onji of the present invention is a crude drug known to have effects such as expectorant, sedation, nourishing tonic, mental stability, and improving memory. The onji of the present invention includes, for example, onji powder which is a crushed product of onji (Polygala tenuifolia) root listed in the 16th revised Japanese Pharmacopoeia or an extract extracted with an organic solvent such as water or ethanol. Ondi extract, or ondi extract powder obtained by pulverizing the extract can be used. Examples of commercially available products include Onji Powder (Tokaimoto Tenkaido), Onji Extract-A (Nippon Powder Chemical), Onji Dry Extract (Alps Pharmaceutical), and the like. In the solid composition of the present invention, the content of the ondi is preferably 10% by mass or more of the whole solid composition, more preferably 30% by mass or more. The upper limit is 90% by mass. In addition, the amount is 250 mg or more, preferably 330 mg or more, more preferably 500 mg or more in the solid composition of the present invention in terms of a crude drug.
本発明のカルボキシメチルスターチナトリウムは粒状のものでも粉末状のものであってもよく、市販品としてはPrimojel（DMV）やエキスプロタブ（木村産業）、GLYCOLYS（ロケットジャパン）等が使用できる。カルボキシメチルスターチナトリウムの含有量は、本発明の固形組成物全体の１質量％〜９０質量％が好ましく、３質量％〜７０質量％が更に好ましい。また、本発明の固形組成物中にオンジを含む場合は、発明の効果の点からオンジ１質量部に対し、０．１〜１質量部が好ましい。
本発明のソルビトールは粒状のものでも粉末状のものであってもよく、市販品としてはNEOSORB（ロケットジャパン）、ソルビトール（三栄源エフエフアイ）、ソルビット（新日本理化）等が使用できる。ソルビトールの含有量は、本発明の固形組成物全体の１質量％〜９０質量％が好ましく、３質量％〜７０質量％が更に好ましい。また、本発明の固形組成物中にオンジを含む場合は、発明の効果の点からオンジ１質量部に対し、０．３〜１質量部が好ましい。
本発明のステビアは粒状のものでも粉末状のものであってもよく、市販品としてはステビMZ（丸善製薬）、ステビロンC（守田化学工業）等が使用できる。ステビアの含有量は、本発明の固形組成物全体の０．００５質量％〜２０質量％が好ましく、０．０１質量％〜１０質量％が更に好ましい。また、本発明の固形組成物中にオンジを含む場合は、発明の効果の点からオンジ１質量部に対し、０．００１〜０．１質量部が好ましい。
本発明のグリチルリチン酸二カリウムは粒状のものでも粉末状のものであってもよく、市販品としてはグリチルリチン酸二カリウム（ALPS薬品工業）、グリチルリチン酸二カリウム（丸善製薬）等が使用できる。グリチルリチン酸二カリウムの含有量は、本発明の固形組成物全体の０．００１質量％〜９０質量％が好ましく、０．０１質量％〜７０質量％が更に好ましい。また、本発明の固形組成物中にオンジを含む場合は、発明の効果の点からオンジ１質量部に対し、０．００１〜１質量部が好ましい。
本発明のマルチトールは粒状のものでも粉末状のものであってもよく、市販品としてはアマルティ（三菱商事フードテック）、レシス（三菱商事フードテック）等が使用できる。マルチトールの含有量は、本発明の固形組成物全体の１質量％〜９０質量％が好ましく、３質量％〜７０質量％が更に好ましい。また、本発明の固形組成物中にオンジを含む場合は、発明の効果の点からオンジ１質量部に対し、０．３〜１質量部が好ましい。
本発明のサッカリンナトリウムは粒状のものでも粉末状のものであってもよく、市販品としてはサッカリンナトリウム（大和化成）等を使用できる。サッカリンナトリウムの含有量は、本発明の固形組成物全体の０．００５質量％〜２０質量％が好ましく、０．０１質量％〜１０質量％が更に好ましい。また、本発明の固形組成物中にオンジを含む場合は、発明の効果の点から、オンジ１質量部に対し、０．００１〜０．１質量部が好ましい。
The sodium carboxymethyl starch of the present invention may be in the form of granules or powder, and commercially available products such as Primojel (DMV), Explotab (Kimura Sangyo), GLYCOLYS (Rocket Japan) and the like can be used. The content of sodium carboxymethyl starch is preferably from 1% by mass to 90% by mass, and more preferably from 3% by mass to 70% by mass, based on the whole solid composition of the present invention. In addition, when the solid composition of the present invention contains an ink, the content is preferably 0.1 to 1 part by mass with respect to 1 part by mass of the ink from the viewpoint of the effect of the present invention.
The sorbitol of the present invention may be granular or powdery, and commercially available products such as NEOSORB (Rocket Japan), Sorbitol (San-Ei Gen FFI), Sorbit (Shin Nihon Rika) and the like can be used. The content of sorbitol is preferably from 1% by mass to 90% by mass, and more preferably from 3% by mass to 70% by mass of the whole solid composition of the present invention. Further, when the solid composition of the present invention contains an onion, the content is preferably 0.3 to 1 part by mass with respect to 1 part by mass of the onion from the viewpoint of the effect of the invention.
The stevia of the present invention may be granular or powdery, and commercially available products such as Stevi MZ (Maruzen Pharmaceutical) and Stevilon C (Morita Chemical Industries) can be used. The content of stevia is preferably from 0.005% by mass to 20% by mass, more preferably from 0.01% by mass to 10% by mass, based on the whole solid composition of the present invention. In addition, when the solid composition of the present invention contains an onion, the amount is preferably 0.001 to 0.1 part by mass with respect to 1 part by mass of the onion from the viewpoint of the effect of the invention.
The dipotassium glycyrrhizinate of the present invention may be granular or powdery, and commercially available products include dipotassium glycyrrhizinate (ALPS Pharmaceutical), dipotassium glycyrrhizinate (Maruzen Pharmaceutical), and the like. The content of dipotassium glycyrrhizinate is preferably from 0.001% by mass to 90% by mass, more preferably from 0.01% by mass to 70% by mass, based on the whole solid composition of the present invention. In addition, when the solid composition of the present invention contains an ink, the content is preferably 0.001 to 1 part by mass with respect to 1 part by mass of the ink from the viewpoint of the effect of the present invention.
The maltitol of the present invention may be in a granular form or a powdery form, and commercially available products such as Amalti (Mitsubishi Foods Tech) and Resis (Mitsubishi Foods Tech) can be used. The content of maltitol is preferably 1% by mass to 90% by mass, and more preferably 3% by mass to 70% by mass based on the whole solid composition of the present invention. Further, when the solid composition of the present invention contains an onion, the content is preferably 0.3 to 1 part by mass with respect to 1 part by mass of the onion from the viewpoint of the effect of the invention.
The saccharin sodium of the present invention may be in the form of granules or powder, and commercially available products include saccharin sodium (Daiwa Kasei). The content of saccharin sodium is preferably 0.005% by mass to 20% by mass, and more preferably 0.01% by mass to 10% by mass of the whole solid composition of the present invention. In addition, when the solid composition of the present invention contains an onion, the amount is preferably 0.001 to 0.1 part by mass based on 1 part by mass of the onion from the viewpoint of the effect of the invention.
本発明の固形組成物とは、２成分以上の成分により構成される常温で固体状の組成物をいい、例えば、混合することにより得られる粉末、造粒により得られる造粒物、粉末や造粒物を打錠することにより得られる錠剤などを挙げることができる。剤型としては、錠剤、顆粒剤、散剤、カプセル剤、チュアブル錠剤、口腔内崩壊錠又はドライシロップ剤等を挙げることができ、特にこれらに限定されるものではない。また、その製造方法は、医薬品の製剤化における一般的な方法で製造することができ、必要に応じて他の公知の添加剤、例えば賦形剤、崩壊剤、結合剤、滑沢剤、抗酸化剤、コーティング剤、着色剤、矯味矯臭剤、界面活性剤、可塑剤等を混合して常法により製造することができる。 The solid composition of the present invention refers to a composition which is solid at room temperature and is composed of two or more components. For example, powder obtained by mixing, granulated product obtained by granulation, Tablets obtained by compressing granules can be mentioned. Examples of the dosage form include tablets, granules, powders, capsules, chewable tablets, orally disintegrating tablets, and dry syrups, and are not particularly limited thereto. In addition, the production method can be produced by a general method in drug formulation, and if necessary, other known additives such as excipients, disintegrants, binders, lubricants, An oxidizing agent, a coating agent, a coloring agent, a flavoring agent, a surfactant, a plasticizer and the like can be mixed and produced by a conventional method.
以下に実施例及び比較例を挙げ、本説明をさらに詳細に説明するが、本発明は以下の実施例に何ら限定されるものではない。なお、表中の単位はｍｇである。
以下表１に実施例１〜２及び比較例１〜４の処方を示す。オンジ（原生薬換算量約８５７ｍｇ）と各成分をガラス瓶内で混合し、固形組成物を調製した。
Hereinafter, the present description will be described in more detail with reference to Examples and Comparative Examples, but the present invention is not limited to the following Examples. The unit in the table is mg.
Table 1 below shows the formulations of Examples 1 and 2 and Comparative Examples 1 to 4. Onji (about 857 mg in terms of crude drug) and each component were mixed in a glass bottle to prepare a solid composition.
（試験例１）
実施例１〜２及び比較例１〜４について25℃60％RH条件下で48時間静置したのち密閉し、65℃条件下で７日保存した。
保存後の固形組成物について、それぞれ組成物中の3’,6-di-O-sinapoyl-sucrose ester含有量を測定し、直後品中の3’,6-di-O-sinapoyl-sucrose ester量に対する残存率を（％）求め、比較例１における3’,6-di-O-sinapoyl-sucrose ester残存率との差を、各組成物における残存率改善度（％）とした。なお、直後品中に含まれる3’,6-di-O-sinapoyl-sucrose esterの含有量は０．８５質量％であった。
(Test Example 1)
Examples 1 and 2 and Comparative Examples 1 to 4 were allowed to stand at 25 ° C. and 60% RH for 48 hours, then sealed, and stored at 65 ° C. for 7 days.
For the solid composition after storage, the 3 ', 6-di-O-sinapoyl-sucrose ester content in each composition was measured, and the 3', 6-di-O-sinapoyl-sucrose ester content in the immediately following product was measured. % Was determined, and the difference from the residual ratio of 3 ′, 6-di-O-sinapoyl-sucrose ester in Comparative Example 1 was defined as the degree of residual ratio improvement (%) in each composition. In addition, the content of 3 ′, 6-di-O-sinapoyl-sucrose ester contained in the product immediately after was 0.85% by mass.
比較例１における3’,6-di-O-sinapoyl-sucrose ester残存率は７５．５％と、経時的な含量低下が認められた。一方、表１より明らかなように、本発明のカルボキシメチルスターチナトリウムもしくはソルビトールを含む実施例１〜２の固形組成物では、残存率（％）が改善した。その他一般的な賦形剤を配合した比較例２〜４の固形組成物では残存率（％）は改善しておらず、カルボキシメチルスターチナトリウム及びソルビトールの配合で特異的な含量低下抑制効果が確認できた。 The residual ratio of 3 ', 6-di-O-sinapoyl-sucrose ester in Comparative Example 1 was 75.5%, indicating a decrease in the content over time. On the other hand, as is clear from Table 1, in the solid compositions of Examples 1 and 2 containing sodium carboxymethyl starch or sorbitol of the present invention, the residual ratio (%) was improved. In the solid compositions of Comparative Examples 2 to 4 in which other common excipients were blended, the residual ratio (%) was not improved, and the specific content reduction inhibitory effect was confirmed by blending sodium carboxymethyl starch and sorbitol. did it.
以下表２に実施例３〜６及び比較例５〜７の処方を示す。オンジ（原生薬換算量約４７６ｍｇ）と各成分をガラス瓶内で混合し、固形組成物を調製した。 Table 2 below shows the formulations of Examples 3 to 6 and Comparative Examples 5 to 7. Onji (about 476 mg in terms of crude drug) and each component were mixed in a glass bottle to prepare a solid composition.
（試験例２）
実施例３〜６及び比較例５〜８について25℃60％RH条件下で48時間静置したのち密閉し、65℃条件下で７日保存した。
保存後の固形組成物について、それぞれ組成物中の3’,6-di-O-sinapoyl-sucrose ester含有量を測定し、直後品中の3’,6-di-O-sinapoyl-sucrose ester量に対する残存率を（％）求め、比較例５における3’,6-di-O-sinapoyl-sucrose ester残存率との差を、各組成物における残存率改善度（％）とした。
(Test Example 2)
Examples 3 to 6 and Comparative Examples 5 to 8 were allowed to stand at 25 ° C. and 60% RH for 48 hours, then sealed, and stored at 65 ° C. for 7 days.
For the solid composition after storage, the 3 ', 6-di-O-sinapoyl-sucrose ester content in each composition was measured, and the 3', 6-di-O-sinapoyl-sucrose ester content in the immediately following product was measured. % Was determined, and the difference from the residual ratio of 3 ′, 6-di-O-sinapoyl-sucrose ester in Comparative Example 5 was defined as the degree of residual ratio improvement (%) in each composition.
表２より明らかなように、本発明のステビア、グリチルリチン酸二カリウム、マルチトールもしくはサッカリンナトリウムを配合した実施例３〜６の固形組成物では、残存率（％）が改善した。比較例６〜８の固形組成物では残存率（％）は改善しておらず、ステビア、グリチルリチン酸二カリウム，マルチトールもしくはサッカリンナトリウムに特異的な含量低下抑制効果が確認できた。 As is clear from Table 2, in the solid compositions of Examples 3 to 6 containing stevia, dipotassium glycyrrhizinate, maltitol or sodium saccharin of the present invention, the residual ratio (%) was improved. In the solid compositions of Comparative Examples 6 to 8, the residual ratio (%) was not improved, and an effect of suppressing a specific decrease in content of stevia, dipotassium glycyrrhizinate, maltitol or saccharin sodium could be confirmed.
以下表３に実施例７〜８及び比較例９〜１１の処方を示す。オンジ（原生薬換算量約５００ｍｇ）を使用し、各成分をガラス瓶内に混合し、水を添加して均一化した後乾燥させ、固形組成物を調製した。 Table 3 below shows the formulations of Examples 7 to 8 and Comparative Examples 9 to 11. Each component was mixed in a glass bottle using Onji (equivalent amount of a crude drug: about 500 mg), and the mixture was homogenized by adding water and then dried to prepare a solid composition.
（試験例３）
実施例７〜８及び比較例９〜１１について25℃60％RH条件下で48時間静置したのち密閉し、65℃条件下で７日保存した。
保存後の固形組成物について、それぞれ組成物中の3’,6-di-O-sinapoyl-sucrose ester含有量を測定し、直後品中の3’,6-di-O-sinapoyl-sucrose ester量に対する残存率を（％）求め、比較例９における3’,6-di-O-sinapoyl-sucrose ester残存率との差を、各組成物における残存率改善度（％）とした。
(Test Example 3)
Examples 7 to 8 and Comparative Examples 9 to 11 were allowed to stand at 25 ° C. and 60% RH for 48 hours, then sealed and stored at 65 ° C. for 7 days.
For the solid composition after storage, the 3 ', 6-di-O-sinapoyl-sucrose ester content in each composition was measured, and the 3', 6-di-O-sinapoyl-sucrose ester content in the immediately following product was measured. % Was determined, and the difference from the 3 ′, 6-di-O-sinapoyl-sucrose ester residual rate in Comparative Example 9 was defined as the residual rate improvement (%) in each composition.
オンジエキスのみ（比較例９）における3’,6-di-O-sinapoyl-sucrose ester残存率は７５．６％と、経時的な含量低下が認められた。表３より明らかなように、比較例１０〜１１の3’,6-di-O-sinapoyl-sucrose esterは、経時的な含量の低下が確認された一方、本発明の実施例７〜８の固形組成物では、残存率（％）が改善しており、特異的含量低下抑制効果が確認できた。 The residual ratio of 3 ', 6-di-O-sinapoyl-sucrose ester in only the ondi extract (Comparative Example 9) was 75.6%, indicating a decrease in the content over time. As is clear from Table 3, 3 ′, 6-di-O-sinapoyl-sucrose ester of Comparative Examples 10 to 11 was confirmed to decrease in content over time, while that of Examples 7 to 8 of the present invention. In the solid composition, the residual ratio (%) was improved, and the effect of suppressing a specific content decrease was confirmed.
本発明により、3’,6-di-O-sinapoyl-sucrose esterの経時的な含量低下を抑制した、商品価値の高い固形組成物の提供が可能となった。 ADVANTAGE OF THE INVENTION According to this invention, it became possible to provide the solid composition of high commercial value which suppressed the time-dependent fall of 3 ', 6-di-O-sinapoyl-sucrose ester.
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