JP4264105B2 - Isosorbide-containing jelly preparation - Google Patents
Isosorbide-containing jelly preparation Download PDFInfo
- Publication number
- JP4264105B2 JP4264105B2 JP2006528598A JP2006528598A JP4264105B2 JP 4264105 B2 JP4264105 B2 JP 4264105B2 JP 2006528598 A JP2006528598 A JP 2006528598A JP 2006528598 A JP2006528598 A JP 2006528598A JP 4264105 B2 JP4264105 B2 JP 4264105B2
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- JP
- Japan
- Prior art keywords
- isosorbide
- jelly
- agar
- added
- preparation
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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Links
- KLDXJTOLSGUMSJ-JGWLITMVSA-N Isosorbide Chemical compound O[C@@H]1CO[C@@H]2[C@@H](O)CO[C@@H]21 KLDXJTOLSGUMSJ-JGWLITMVSA-N 0.000 title claims description 102
- 229960002479 isosorbide Drugs 0.000 title claims description 102
- 235000015110 jellies Nutrition 0.000 title claims description 68
- 239000008274 jelly Substances 0.000 title claims description 68
- 238000002360 preparation method Methods 0.000 title claims description 54
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- 239000008272 agar Substances 0.000 claims description 47
- 239000000843 powder Substances 0.000 claims description 29
- 244000299461 Theobroma cacao Species 0.000 claims description 28
- 235000005764 Theobroma cacao ssp. cacao Nutrition 0.000 claims description 27
- 235000005767 Theobroma cacao ssp. sphaerocarpum Nutrition 0.000 claims description 27
- 235000001046 cacaotero Nutrition 0.000 claims description 27
- 239000000203 mixture Substances 0.000 claims description 26
- 238000009472 formulation Methods 0.000 claims description 21
- 238000000034 method Methods 0.000 claims description 15
- 238000004090 dissolution Methods 0.000 claims description 14
- 238000007922 dissolution test Methods 0.000 claims description 8
- 235000009470 Theobroma cacao Nutrition 0.000 claims 1
- 235000019658 bitter taste Nutrition 0.000 description 28
- 238000012360 testing method Methods 0.000 description 23
- 239000007788 liquid Substances 0.000 description 22
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 22
- 238000010828 elution Methods 0.000 description 21
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- 239000003349 gelling agent Substances 0.000 description 14
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- 239000003795 chemical substances by application Substances 0.000 description 7
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- 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 6
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 6
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- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 3
- LUEWUZLMQUOBSB-FSKGGBMCSA-N (2s,3s,4s,5s,6r)-2-[(2r,3s,4r,5r,6s)-6-[(2r,3s,4r,5s,6s)-4,5-dihydroxy-2-(hydroxymethyl)-6-[(2r,4r,5s,6r)-4,5,6-trihydroxy-2-(hydroxymethyl)oxan-3-yl]oxyoxan-3-yl]oxy-4,5-dihydroxy-2-(hydroxymethyl)oxan-3-yl]oxy-6-(hydroxymethyl)oxane-3,4,5-triol Chemical compound O[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@@H](O[C@@H]2[C@H](O[C@@H](OC3[C@H](O[C@@H](O)[C@@H](O)[C@H]3O)CO)[C@@H](O)[C@H]2O)CO)[C@H](O)[C@H]1O LUEWUZLMQUOBSB-FSKGGBMCSA-N 0.000 description 2
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 2
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- SRBFZHDQGSBBOR-IOVATXLUSA-N D-xylopyranose Chemical compound O[C@@H]1COC(O)[C@H](O)[C@H]1O SRBFZHDQGSBBOR-IOVATXLUSA-N 0.000 description 2
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- 239000000341 volatile oil Substances 0.000 description 2
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
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- 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 1
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Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
- A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/08—Drugs for disorders of the alimentary tract or the digestive system for nausea, cinetosis or vertigo; Antiemetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/16—Otologicals
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/10—Antioedematous agents; Diuretics
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Biomedical Technology (AREA)
- Hospice & Palliative Care (AREA)
- Zoology (AREA)
- Nutrition Science (AREA)
- Physiology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Urology & Nephrology (AREA)
- Otolaryngology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Ophthalmology & Optometry (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
本発明は、医薬品の分野の発明であり、苦みが強くて服用しにくいイソソルビドの製剤工夫に関するものである。 The present invention is an invention in the field of pharmaceuticals, and relates to a formulation of isosorbide that is hard to take and difficult to take.
イソソルビドはメニエール治療薬であり、消化管から速やかに吸収されるが、体内において代謝されないため、血清浸透圧を高める。その結果、本薬物は、利尿作用、脳圧降下作用、眼圧降下作用、内リンパ圧降下作用を示す。イソソルビドはまた、メニエール病の症状であるめまい等の発作が発現してから頓服として服用することもしばしばあるため、服用後速やかにその薬効が発現する必要がある。一般に薬物は、服用後消化管内で溶解し吸収されることにより薬効を発現するため、イソソルビドが速やかに薬効を発現するためには、消化管内で速やかに溶解する必要がある。イソソルビドを主成分とする医薬品としては、内服液剤が商品化されている。液剤が剤形として選択されている理由として、液剤は既に薬物であるイソソルビドが溶解状態にあるため、速やかに薬効を発現することが期待できるためである。 Isosorbide is a Meniere drug that is rapidly absorbed from the gastrointestinal tract but is not metabolized in the body, thus increasing serum osmotic pressure. As a result, this drug exhibits diuretic action, brain pressure lowering action, intraocular pressure lowering action, and endolymphatic pressure lowering action. Isosorbide is also often taken as a pill after the occurrence of seizures such as dizziness, which is a symptom of Meniere's disease, and thus its medicinal effect needs to be manifested immediately after taking it. In general, a drug develops a medicinal effect by being dissolved and absorbed in the gastrointestinal tract after taking it. Therefore, in order for isosorbide to express a medicinal effect quickly, it is necessary to dissolve it quickly in the gastrointestinal tract. As a pharmaceutical having isosorbide as a main component, an internal solution is commercialized. The reason why the liquid agent is selected as the dosage form is that the liquid agent is already in a dissolved state, so that it can be expected to quickly exhibit a medicinal effect.
一方、この薬物は非常に苦いことが特徴である。そのため、上記液剤においても、甘味剤等の添加による苦味低減がはかられてはいるが、その効果は十分なものではない。これは、苦味を有するイソソルビドを1回に21g〜28gも服用する必要があるため、患者が1回に服用する液剤の量を極力少なくすることを目的として、液剤中のイソソルビド濃度を70w/v%程度に高くする必要があるためである。このような理由で、イソソルビドの苦味低減は、非常に困難なものとなっている。しかも、市販液剤は、苦み防止を目的として添加された矯味剤の酸味が強く、後苦味が強く現れ、しばしば患者がイソソルビドを服用することを困難としている。従って、イソソルビドの苦味を低減して服用性を改善することが、医療現場において非常に望まれている。 On the other hand, this drug is very bitter. For this reason, even in the above liquid preparation, although bitterness reduction by adding a sweetening agent or the like has been made, the effect is not sufficient. This is because it is necessary to take 21g to 28g of isosorbide having a bitter taste at a time, so that the concentration of isosorbide in the solution is set to 70w / v for the purpose of minimizing the amount of the solution taken by the patient at one time. This is because it needs to be as high as about%. For these reasons, it is very difficult to reduce the bitterness of isosorbide. In addition, commercially available liquid preparations have a strong sourness added to prevent bitterness and a strong aftertaste, which often makes it difficult for patients to take isosorbide. Therefore, reducing the bitter taste of isosorbide and improving the dosage is highly desired in the medical field.
イソソルビドのように苦み等の不快な味を示す薬物は多く、この不快な味を改善することは医薬品の開発において重要な課題であるため、種々の検討がなされている。例えば、苦み成分を含む錠剤については、糖衣を施したりフィルムコーティングを施すことにより、苦みの低減が図られている。また、苦み成分を含む各種散剤、細粒剤、顆粒剤に対しては、錠剤と同様にフィルムコーティングを施すこと、あるいは白糖などの甘味剤を添加することにより苦みの低減が図られている。さらに、不溶性基剤に苦み成分を含有させ口腔内での溶出を抑制する方法(特開昭54-95719、特開昭63-303928、特開平2-288821、特開平4-187629、特開平4-327528、特開平6-501027等)、苦みを低減する添加物として蛋白質−脂質複合体を添加する方法(特開平6-316537)、精油または精油成分を配合する方法(特開平5-255126)、酸性リン脂質もしくはそのリゾ体を添加する方法(特開平7-67552)、カカオ末を添加する方法(特開2000-95710)などが開示されている。これらはいずれも固形製剤に関するものであり、苦味成分を1g以下程度の少量含むような固形製剤の苦味低減は、これらの方法で比較的容易に実施することができる。 There are many drugs that exhibit an unpleasant taste such as bitterness, such as isosorbide, and improvement of this unpleasant taste is an important issue in the development of pharmaceuticals, and thus various studies have been made. For example, for tablets containing a bitter component, bitterness is reduced by applying sugar coating or film coating. In addition, various powders, fine granules, and granules containing bitter ingredients are reduced in bitterness by film coating as in the case of tablets, or by adding sweeteners such as sucrose. Further, a method for containing a bitter component in an insoluble base to suppress dissolution in the oral cavity (JP 54-95719, JP 63-303928, JP 2-88821, JP 4-187629, JP 4) -327528, JP-A-6-501027, etc.), a method of adding a protein-lipid complex as an additive to reduce bitterness (JP-A-6-316537), a method of blending essential oils or essential oil components (JP-A-5-255126) In addition, a method of adding acidic phospholipid or its lyso form (JP-A-7-67552), a method of adding cacao powder (JP-A 2000-95710) and the like are disclosed. These all relate to solid preparations, and the bitterness reduction of solid preparations containing a small amount of bitterness components of about 1 g or less can be carried out relatively easily by these methods.
一方、液剤の服用性改善の例は、甘味剤を添加するなどの一般的な方法を除くと、有効な方法は見当たらない。ゼリー化による方法(特開2001-226293)も開示されているが、この方法では、苦みを示す有効成分の溶出を抑制するため、バイオアベイラビリティーが低下したり、薬効の発現が遅くなることが推測される。 On the other hand, no effective method can be found in examples of improving the ingestion of liquids, except for general methods such as adding a sweetener. Although a method using jelly (Japanese Patent Laid-Open No. 2001-226293) is also disclosed, in this method, since the elution of an active ingredient exhibiting bitterness is suppressed, bioavailability may be reduced or the onset of drug efficacy may be delayed. Guessed.
メニエール病治療薬であるイソソルビド液剤は、前述のように、苦味が強くその服用性改善が強く望まれているが、いまだに、服用性のよいイソソルビド製剤はできていない。そこで、イソソルビド製剤に必要とされる速やかな薬効発現という特性を損なわずに、服用性の改善されたイソソルビド製剤を提供することを課題とする。 As described above, the isosorbide liquid agent, which is a treatment for Meniere's disease, has a strong bitter taste and is strongly desired to improve its ingestibility. However, an isosorbide preparation with good ingestibility has not yet been made. Then, let it be a subject to provide the isosorbide formulation by which taking property was improved, without impairing the characteristic of the rapid onset of a drug effect required for an isosorbide formulation.
本発明者らは、苦くて飲みにくいイソソルビド液剤の服用性を改善することを目的として鋭意検討した。まず、第一に各種のゲル化剤を使用してイソソルビドを含有するゼリー製剤の調製を試みた。その結果、ゼリー化によりイソソルビドの服用性改善効果は認められたが、懸念されていたように、このゼリー製剤からのイソソルビドの溶出は、液剤より顕著に遅くなることが判明した。これは、ゲル化により苦味成分であるイソソルビドの溶出が抑制されたことによると考えられた。そこで本発明者らは、さらに鋭意検討した結果、驚くことにゲル化剤として寒天を用いることにより、イソソルビドは液剤と同様にゼリー製剤から速やかに溶出し、服用性も改善されることを見出した。さらに、苦みを改善するために、カカオ末を添加した結果、苦みは相乗的に低減し、大変服用し易くなることを見出した。本発明者らは、かかる知見に基づき本発明を完成するに至った。 The present inventors diligently studied for the purpose of improving the dosage of isosorbide solution that is bitter and difficult to drink. First, preparation of a jelly preparation containing isosorbide was attempted using various gelling agents. As a result, it was found that the effect of isosorbide was improved by jelly formation, but as was concerned, it was found that the elution of isosorbide from this jelly preparation was significantly slower than the liquid preparation. This was considered to be due to suppression of elution of isosorbide, which is a bitter component, due to gelation. Therefore, as a result of further intensive studies, the present inventors have surprisingly found that by using agar as a gelling agent, isosorbide can be quickly eluted from the jelly preparation in the same manner as the liquid preparation, and the ingestion can be improved. . Furthermore, the present inventors have found that as a result of adding cacao powder to improve bitterness, bitterness is reduced synergistically and becomes very easy to take. Based on this finding, the present inventors have completed the present invention.
すなわち、本発明は、イソソルビド及び寒天を含むことを特徴とする、イソソルビド含有ゼリー製剤である。本発明の製剤は、好ましくは、更にカカオ末を含む。また、寒天の添加量は、ゼリー製剤全体の0.3〜2w/w%とするのが好ましい。 That is, this invention is an isosorbide containing jelly formulation characterized by including isosorbide and agar. The preparation of the present invention preferably further contains cacao powder. The amount of agar added is preferably 0.3-2 w / w% of the total jelly preparation.
本発明はまた、イソソルビド含有ゼリー製剤の製造方法をも提供する。すなわち、本発明法は、少なくとも寒天、イソソルビド及び水を混合し、加熱溶解した後、常温以下に冷却することを特徴とする、イソソルビド含有ゼリー製剤の製造方法である。ここで、 寒天、イソソルビド及び水とともに、更にカカオ末を添加混合することが好ましい。 The present invention also provides a method for producing an isosorbide-containing jelly preparation. That is, the method of the present invention is a method for producing an isosorbide-containing jelly preparation characterized in that at least agar, isosorbide and water are mixed, heated and dissolved, and then cooled to room temperature or lower. Here, it is preferable to add and mix cacao powder together with agar, isosorbide and water.
本発明のイソソルビド含有ゼリー製剤を利用することにより、患者はイソソルビドの強い苦味を気にすることなく服用できるようになり、服薬コンプライアンスの向上が期待できる。また、本発明の製剤は、内服液剤と同様に消化管内で速やかにイソソルビドを溶出するため、内服液剤と同様に速やかに薬効が発現される。 By utilizing the isosorbide-containing jelly preparation of the present invention, the patient can take it without worrying about the strong bitter taste of isosorbide, and an improvement in medication compliance can be expected. Moreover, since the formulation of this invention elutes isosorbide rapidly in a digestive tract like an internal use liquid agent, a drug effect is rapidly expressed like an internal use liquid agent.
以下、本発明のゼリー製剤について、更に詳細に説明する。
本発明製剤中のイソソルビドの含有濃度は特に規定されるものではないが、50〜80w/w%であることが望ましい。これは、ゼリー製剤一定量中のイソソルビドの含量を少なくすれば、苦味が軽減されるのは当然であるが、イソソルビドの1回服用量は21g〜28gと非常に多いため、ゼリー製剤一定量中のイソソルビド含量が少ない場合、1回に多量のゼリー製剤を服用することが必要となり、イソソルビドの服用を逆に困難なものとしてしまう。Hereinafter, the jelly preparation of the present invention will be described in more detail.
The concentration of isosorbide contained in the preparation of the present invention is not particularly limited, but is preferably 50 to 80 w / w%. It is natural that if the content of isosorbide in a certain amount of jelly preparation is reduced, the bitter taste is reduced, but the single dose of isosorbide is very high, 21g to 28g. When the content of isosorbide is small, it is necessary to take a large amount of jelly preparation at a time, which makes it difficult to take isosorbide.
本発明のゼリー製剤から、イソソルビドは液剤と同様に速やかな溶出を示すことから、服用後速やかな薬効発現が期待できる。ここで速やかな溶出とは、日本薬局方 溶出試験法において、15分後のゼリー製剤からのイソソルビドの溶出が85%以上であることを意味し、この条件を満たす医薬組成物は、消化管内でも速やかにイソソルビドを溶出し、液剤と同様に直ちに薬効を発現する。 From the jelly preparation of the present invention, isosorbide exhibits rapid elution as in the case of liquids, so that rapid drug efficacy can be expected after taking. Here, rapid dissolution means that the dissolution of isosorbide from the jelly preparation after 15 minutes is 85% or more in the Japanese Pharmacopoeia Dissolution Test Method. Isosorbide is eluted quickly, and the drug is immediately effective as well as liquid.
本発明に使用する寒天はガラクトースを基本骨格とする多糖類からなり、原料である海藻の起源や製造方法により分子量や官能基が異なるため、その特性も異なる。従ってその添加量については一概に規定できないが、ゼリー製剤全重量に対して0.3〜2w/w%がよく、さらに好ましくは0.5〜1.5 w/w%がよい。寒天の使用量を上記の範囲より少なくした場合、ゼリー製剤からのイソソルビドの溶出には影響しないが、ゼリー強度が低下して苦味の低減効果が少なくなる。また、ゲル化しないこともある。逆に使用量を増加させた場合には、寒天の溶解不良が生じたり、ゲル化前の液の粘度が非常に高いため、容器への充填が困難となる場合がある。さらに、ゼリーが固くなりすぎて服用感が悪くなるとともに、ゼリー製剤からのイソソルビドの溶出が遅くなる。従って、イソソルビドの苦味を低減して服用感を改善しかつゼリー製剤からのイソソルビドの迅速な溶出を確保するには、寒天の量は上記の範囲が好ましい。また、ゲル化剤としては、寒天を単独で使用することが望ましいが、その他のゲル化剤を添加することもできる。寒天に添加するゲル化剤としては、カラギーナン、キサンタンガム、ローカストビーンガム、アルギン酸塩等を例示することができる。しかし、これらを大量に添加することは、寒天の特性を損なうため、添加量は少な目にすべきである。 The agar used in the present invention is composed of a polysaccharide having galactose as a basic skeleton, and has different molecular weights and functional groups depending on the origin of the seaweed as a raw material and the production method. Accordingly, the amount added cannot be generally defined, but is preferably 0.3 to 2 w / w%, more preferably 0.5 to 1.5 w / w%, based on the total weight of the jelly preparation. When the amount of agar used is less than the above range, it does not affect the elution of isosorbide from the jelly preparation, but the jelly strength decreases and the bitterness reduction effect decreases. Moreover, it may not gel. Conversely, when the amount used is increased, poor dissolution of the agar may occur, or the viscosity of the liquid before gelation may be very high, making it difficult to fill the container. Furthermore, the jelly becomes too hard and the feeling of administration becomes worse, and the elution of isosorbide from the jelly preparation is delayed. Therefore, the amount of agar is preferably in the above range in order to reduce the bitter taste of isosorbide to improve the feeling of taking and to ensure rapid dissolution of isosorbide from the jelly preparation. As the gelling agent, it is desirable to use agar alone, but other gelling agents can also be added. Examples of the gelling agent added to the agar include carrageenan, xanthan gum, locust bean gum, alginate and the like. However, the addition of a large amount of these impairs the properties of the agar, so the addition amount should be small.
本発明のイソソルビドの苦味低減による服用性の改善効果は、カカオ末を添加することにより増強する。その添加量は、ゼリー製剤全重量に対して0.1〜5w/w%が最適である。さらに必要に応じて、ブドウ糖、果糖、麦芽糖、キシロース、蜂蜜、白糖(蔗糖)、水飴、ソルビトール、マンニトール、キシリトール、マルチトール、粉末還元麦芽糖水飴、ステビア抽出物、アスパルテーム、チョコレートフレーバー、サッカリンナトリウム等の甘味剤あるいはコーヒー等の嗜好品あるいは香料を添加してもよい。このうちイソソルビドの苦みに対して、チョコレートフレーバー、サッカリンナトリウムの組み合わせが最も好ましい。 The effect of improving ingestibility by reducing the bitterness of isosorbide of the present invention is enhanced by adding cacao powder. The addition amount is optimally 0.1 to 5 w / w% with respect to the total weight of the jelly preparation. In addition, glucose, fructose, maltose, xylose, honey, sucrose (sucrose), starch syrup, sorbitol, mannitol, xylitol, maltitol, powdered reduced maltose starch syrup, stevia extract, aspartame, chocolate flavor, saccharin sodium, etc. An agent, a favorite product such as coffee, or a fragrance may be added. Of these, the combination of chocolate flavor and sodium saccharin is most preferable for the bitterness of isosorbide.
本発明製剤の製造方法、即ちゼリー化は、寒天、イソソルビド、必要に応じてカカオ末、香料、甘味剤に水を加えて、90〜100℃で数分間撹拌溶解した後、常温以下に冷却して行う。ここで、添加物の添加順序は特に規定されない。また、場合により、さらにpH調整剤、着色剤、保存剤等の添加物を含有することができる。調製されたイソソルビド含有ゼリー製剤は、カップ、バッグ、チューブ等に収容、包装することができる。 The preparation method of the present invention, that is, jelly formation is carried out by adding water to agar, isosorbide, cacao powder, fragrance, and sweetener as necessary, stirring and dissolving at 90 to 100 ° C. for several minutes, and then cooling to room temperature or lower. Do it. Here, the order of addition of the additives is not particularly defined. Moreover, additives, such as pH adjuster, a coloring agent, and a preservative, can be further contained depending on the case. The prepared isosorbide-containing jelly preparation can be housed and packaged in a cup, bag, tube or the like.
以下、実施例及び比較例を挙げて、本発明をさらに詳しく説明する。 Hereinafter, the present invention will be described in more detail with reference to Examples and Comparative Examples.
実施例1(イソソルビド+寒天+添加剤)
水約60mLに寒天1.2g、クエン酸0.24g、無水リン酸水素二ナトリウム0.48g及びサッカリンナトリウム0.6gを加えて、90〜100℃で数分間加熱撹拌溶解した。次にイソソルビド140gを少量ずつ加えて溶かし、更にカカオ末0.4g及びチョコレートフレーバー0.2gを加えて均一に混合し、カップに充填して常温まで冷却した。 Example 1 (isosorbide + agar + additive)
1.2 g of agar, 0.24 g of citric acid, 0.48 g of anhydrous sodium hydrogenphosphate and 0.6 g of saccharin sodium were added to about 60 mL of water, and the mixture was heated and dissolved at 90 to 100 ° C. for several minutes with stirring. Next, 140 g of isosorbide was added little by little, and 0.4 g of cacao powder and 0.2 g of chocolate flavor were added and mixed uniformly, filled into a cup, and cooled to room temperature.
実施例2(イソソルビド+寒天)
水約60mLに寒天1.2gを加えて、90〜100℃で数分間加熱撹拌溶解した。次にイソソルビド140gを少量ずつ加えて溶かし均一に混合した後、カップに充填して常温まで冷却した。 Example 2 (isosorbide + agar)
1.2 g of agar was added to about 60 mL of water, and dissolved by stirring at 90-100 ° C. for several minutes. Next, 140 g of isosorbide was added little by little to dissolve and mixed uniformly, then filled into a cup and cooled to room temperature.
実施例3[イソソルビド+(寒天+カラギーナン)+添加剤]
水約60mLに寒天1.2g、カラギーナン0.6g、リン酸水素二カリウム0.6g、リン酸二水素カリウム0.1g、塩化カリウム0.03g及びサッカリンナトリウム0.6gを加えて、90〜100℃で数分間加熱撹拌溶解した。次にイソソルビド140gを少量ずつ加えて溶かし、更にカカオ末0.4g及びチョコレートフレーバー0.2gを加えて均一に混合し、カップに充填して常温まで冷却した。 Example 3 [Isosorbide + (agar + carrageenan) + additive]
Add 1.2 g of agar, 0.6 g of carrageenan, 0.6 g of dipotassium hydrogen phosphate, 0.1 g of potassium dihydrogen phosphate, 0.03 g of potassium chloride and 0.6 g of sodium saccharin to about 60 mL of water, and dissolve with heating and stirring at 90-100 ° C for several minutes. did. Next, 140 g of isosorbide was added little by little, and 0.4 g of cacao powder and 0.2 g of chocolate flavor were added and mixed uniformly, filled into a cup, and cooled to room temperature.
実施例4[イソソルビド+(寒天+キサンタンガム)+添加剤]
水約60mLに寒天1.2g、キサンタンガム0.3g、リン酸水素二カリウム0.6g、リン酸二水素カリウム0.1g、塩化カリウム0.03g及びサッカリンナトリウム0.6gを加えて、90〜100℃で数分間加熱撹拌溶解した。次にイソソルビド140gを少量ずつ加えて溶かし、更にカカオ末0.4g及びチョコレートフレーバー0.2gを加えて均一に混合し、カップに充填して常温まで冷却した。 Example 4 [Isosorbide + (agar + xanthan gum) + additive]
Add 1.2 g of agar, 0.3 g of xanthan gum, 0.6 g of dipotassium hydrogen phosphate, 0.1 g of potassium dihydrogen phosphate, 0.03 g of potassium chloride and 0.6 g of sodium saccharin to about 60 mL of water, and dissolve with heating and stirring at 90-100 ° C for several minutes. did. Next, 140 g of isosorbide was added little by little, and 0.4 g of cacao powder and 0.2 g of chocolate flavor were added and mixed uniformly, filled into a cup, and cooled to room temperature.
実施例5[イソソルビド+(寒天+アルギン酸ナトリウム)+添加剤]
水約60mLに寒天1.2g、アルギン酸ナトリウム0.3g、リン酸水素二カリウム0.6g、リン酸二水素カリウム0.1g、塩化カリウム0.03g及びサッカリンナトリウム0.6gを加えて、90〜100℃で数分間加熱撹拌溶解した。次にイソソルビド140gを少量ずつ加えて溶かし、更にカカオ末0.4g及びチョコレートフレーバー0.2gを加えて均一に混合し、カップに充填して常温まで冷却した。 Example 5 [Isosorbide + (agar + sodium alginate) + additive]
Add 1.2 g of agar, 0.3 g of sodium alginate, 0.6 g of dipotassium hydrogen phosphate, 0.1 g of potassium dihydrogen phosphate, 0.03 g of potassium chloride and 0.6 g of sodium saccharin to about 60 mL of water, and heat and stir at 90-100 ° C for several minutes. Dissolved. Next, 140 g of isosorbide was added little by little, and 0.4 g of cacao powder and 0.2 g of chocolate flavor were added and mixed uniformly, filled into a cup, and cooled to room temperature.
実施例6(寒天量の増減)
水約60mLに寒天0.6g、クエン酸0.24g、無水リン酸水素二ナトリウム0.48g及びサッカリンナトリウム0.6gを加えて、90〜100℃で数分間加熱撹拌溶解した。次にイソソルビド140gを少量ずつ加えて溶かし、更にカカオ末0.4g及びチョコレートフレーバー0.2gを加えて均一に混合し、カップに充填して常温まで冷却した。 Example 6 (Increase / decrease in the amount of agar)
0.6 g of agar, 0.24 g of citric acid, 0.48 g of anhydrous disodium hydrogen phosphate and 0.6 g of sodium saccharin were added to about 60 mL of water, and the mixture was stirred and dissolved at 90-100 ° C. for several minutes. Next, 140 g of isosorbide was added little by little, and 0.4 g of cacao powder and 0.2 g of chocolate flavor were added and mixed uniformly, filled into a cup, and cooled to room temperature.
実施例7(寒天量の増減)
水約60mLに寒天3g、クエン酸0.24g、無水リン酸水素二ナトリウム0.48g及びサッカリンナトリウム0.6gを加えて、90〜100℃で数分間加熱撹拌溶解した。次にイソソルビド140gを少量ずつ加えて溶かし、更にカカオ末0.4g及びチョコレートフレーバー0.2gを加えて均一に混合し、カップに充填して常温まで冷却した。 Example 7 (Increase / decrease in the amount of agar)
3 g of agar, 0.24 g of citric acid, 0.48 g of anhydrous disodium hydrogen phosphate and 0.6 g of sodium saccharin were added to about 60 mL of water, and dissolved by stirring with heating at 90 to 100 ° C. for several minutes. Next, 140 g of isosorbide was added little by little, and 0.4 g of cacao powder and 0.2 g of chocolate flavor were added and mixed uniformly, filled into a cup, and cooled to room temperature.
実施例8(寒天量の増減)
水約60mLに寒天7g、クエン酸0.24g、無水リン酸水素二ナトリウム0.48g及びサッカリンナトリウム0.6gを加えて、90〜100℃で数分間加熱撹拌溶解した。次にイソソルビド140gを少量ずつ加えて溶かし、更にカカオ末0.4g及びチョコレートフレーバー0.2gを加えて均一に混合し、カップに充填して常温まで冷却した。 Example 8 (Increase / decrease in the amount of agar)
7 g of agar, 0.24 g of citric acid, 0.48 g of anhydrous disodium hydrogen phosphate and 0.6 g of sodium saccharin were added to about 60 mL of water, and the mixture was stirred and dissolved at 90-100 ° C. for several minutes. Next, 140 g of isosorbide was added little by little, and 0.4 g of cacao powder and 0.2 g of chocolate flavor were added and mixed uniformly, filled into a cup, and cooled to room temperature.
対照例1(液剤)
イソソルビド70gに水30mLを加えて溶かした。 Control 1 (Liquid)
30 g of water was added to 70 g of isosorbide and dissolved.
対照例2(イソソルビド+ペクチン+添加剤)
水約55mLにペクチン1g、クエン酸4.8g及びサッカリンナトリウム0.6gを加えて、90〜100℃で数分間加熱撹拌溶解した。次にイソソルビド140gを少量ずつ加えて溶かし、更にカカオ末0.4g及びチョコレートフレーバー0.2gを加えて均一に混合し、カップに充填して常温まで冷却した。 Control example 2 (isosorbide + pectin + additive)
1 g of pectin, 4.8 g of citric acid and 0.6 g of sodium saccharin were added to about 55 mL of water, and dissolved by stirring with heating at 90 to 100 ° C. for several minutes. Next, 140 g of isosorbide was added little by little, and 0.4 g of cacao powder and 0.2 g of chocolate flavor were added and mixed uniformly, filled into a cup, and cooled to room temperature.
対照例3(イソソルビド+ローカストビーンガム+キサンタンガム)
水約60mLにローカストビーンガム0.56g、キサンタンガム0.56g、リン酸水素二カリウム0.3g及びサッカリンナトリウム0.6gを加えて、90〜100℃で数分間加熱撹拌溶解した。次にイソソルビド140gを少量ずつ加えて溶かし、更にカカオ末0.4g及びチョコレートフレーバー0.2gを加えて均一に混合し、カップに充填して常温まで冷却した。 Control Example 3 (Isosorbide + locust bean gum + xanthan gum)
Locust bean gum 0.56 g, xanthan gum 0.56 g, dipotassium hydrogen phosphate 0.3 g and saccharin sodium 0.6 g were added to about 60 mL of water, and dissolved by stirring at 90-100 ° C. for several minutes. Next, 140 g of isosorbide was added little by little, and 0.4 g of cacao powder and 0.2 g of chocolate flavor were added and mixed uniformly, filled into a cup, and cooled to room temperature.
対照例4(イソソルビド+グルコマンナン+キサンタンガム)
水約60mLにグルコマンナン0.5g、キサンタンガム0.5g及びサッカリンナトリウム0.6gを加えて、90〜100℃で数分間加熱撹拌溶解した。次にイソソルビド140gを少量ずつ加えて溶かし、更にカカオ末0.4g及びチョコレートフレーバー0.2gを加えて均一に混合し、カップに充填して常温まで冷却した。 Control Example 4 (isosorbide + glucomannan + xanthan gum)
To about 60 mL of water, 0.5 g of glucomannan, 0.5 g of xanthan gum and 0.6 g of saccharin sodium were added and dissolved by stirring at 90-100 ° C. for several minutes. Next, 140 g of isosorbide was added little by little, and 0.4 g of cacao powder and 0.2 g of chocolate flavor were added and mixed uniformly, filled into a cup, and cooled to room temperature.
対照例5(イソソルビド+ローカストビーンガム+キサンタンガム)
水約55mLにローカストビーンガム1.4g、キサンタンガム1.4g、クエン酸0.24g、無水リン酸水素二ナトリウム0.48g及びサッカリンナトリウム0.6gを加えて、90〜100℃で数分間加熱撹拌溶解した。次にイソソルビド140gを少量ずつ加えて溶かし、更にカカオ末0.4g及びチョコレートフレーバー0.2gを加えて均一に混合し、カップに充填して常温まで冷却した。 Control Example 5 (Isosorbide + locust bean gum + xanthan gum)
Locust bean gum (1.4 g), xanthan gum (1.4 g), citric acid (0.24 g), anhydrous disodium hydrogen phosphate (0.48 g), and saccharin sodium (0.6 g) were added to about 55 mL of water, and dissolved by stirring at 90 to 100 ° C. for several minutes. Next, 140 g of isosorbide was added little by little, and 0.4 g of cacao powder and 0.2 g of chocolate flavor were added and mixed uniformly, filled into a cup, and cooled to room temperature.
対照例6(イソソルビド+ジェランガム)
水約60mLにジェランガム0.9g、リン酸水素二カリウム0.6g、クエン酸ナトリウム1g及びサッカリンナトリウム0.6gを加えて、90〜100℃で数分間加熱撹拌溶解した。次にイソソルビド140gを少量ずつ加えて溶かし、更にカカオ末0.4g及びチョコレートフレーバー0.2gを加えて均一に混合し、カップに充填して常温まで冷却した。 Control 6 (isosorbide + gellan gum)
Gellan gum (0.9 g), dipotassium hydrogen phosphate (0.6 g), sodium citrate (1 g) and saccharin sodium (0.6 g) were added to about 60 mL of water, and the mixture was heated and dissolved at 90 to 100 ° C. for several minutes. Next, 140 g of isosorbide was added little by little, and 0.4 g of cacao powder and 0.2 g of chocolate flavor were added and mixed uniformly, filled into a cup, and cooled to room temperature.
[試験例1](官能試験)
5名の被験者により、実施例1、実施例2及び対照例1の服用感を評価した。ここでは、被験者はゼリー製剤約5gを口中に入れ、数回咀嚼して評価した。また、液剤はその約5gを口の中に入れて評価した。評価は、苦みを感じない場合を1とし非常に強い苦みがあり服用し難いを5とする 5段階の評価により行った。その試験結果を表1に示す。[Test Example 1] (Sensory test)
The feeling of taking in Example 1, Example 2 and Control Example 1 was evaluated by 5 subjects. Here, the subject put about 5 g of the jelly preparation into the mouth and chewed several times for evaluation. In addition, about 5 g of the liquid agent was put in the mouth and evaluated. The evaluation was performed based on a five-step evaluation, where 1 was a case where no bitterness was felt and 5 was a very strong bitterness that was difficult to take. The test results are shown in Table 1.
イソソルビド及び寒天からなるゼリー製剤は、イソソルビド液の服用感を改善した。通常、カカオ末は、苦み物質に対して数十%から数百%添加しないと効果を発揮しないが、実施例1においては、苦味物質であるイソソルビドが70%の高濃度で含まれているにも関わらず、寒天とカカオ末との相乗効果により、少量のカカオ末で優れた苦味低減効果を示すことが確認された。 The jelly preparation consisting of isosorbide and agar improved the feeling of taking the isosorbide solution. Normally, cacao powder does not exert its effect unless it is added to several tens to hundreds of percent of the bitter substance. Nevertheless, due to the synergistic effect of agar and cacao powder, it was confirmed that a small amount of cacao powder showed an excellent bitterness reducing effect.
[試験例2](官能試験及びゲルの硬さ;寒天量の影響)
6名の被験者により、実施例1、実施例6、実施例7及び実施例8のゼリー製剤の服用感を比較し、添加する寒天量の影響を検討した。被検者は、ゼリー製剤約5gを口中に入れ数回咀嚼して評価した。苦みの評価についてはいずれのゼリー製剤も苦みが低減されているため、評価基準を設定することが困難であったため、相対評価として苦みが少ない順に順位づけした。また、総合的服用し易さは非常に服用しやすいを1、服用し難いを5とする5段階評価により行った。また、ゼリーの硬さは、レオメーターを用いて一定面積のプランジャーを用い、ゼリーを60mm/minの速度で圧縮して、ゼリーが破断するときの強度を測定した。その試験結果を表2、表3及び図1に示す。[Test Example 2] (Sensory test and gel hardness; influence of agar amount)
Six subjects compared the sensation of taking the jelly preparations of Example 1, Example 6, Example 7 and Example 8, and examined the effect of the amount of agar added. The subject put about 5 g of jelly preparation into the mouth and chewed several times for evaluation. As for the evaluation of bitterness, since bitterness was reduced in any jelly preparation, it was difficult to set an evaluation standard. In addition, the overall ease of taking was evaluated based on a five-level evaluation, with 1 being very easy to take and 5 being difficult to take. The hardness of the jelly was determined by measuring the strength at which the jelly breaks by compressing the jelly at a speed of 60 mm / min using a rheometer with a plunger having a constant area. The test results are shown in Table 2, Table 3, and FIG.
実施例6は相対的に苦味を低減する効果が少なかった。その原因はこのゲルはやわらかくて口の中で崩れやすく、寒天とカカオ末の相乗効果が少なかったためと考えられた。逆に寒天の添加量が多い実施例8のゲルは図1に示すように非常に固く、アンケート結果より、苦味の低減効果は十分に確認されたものの服用感が非常に悪かった。また、製造時の粘度が非常に高く、大量生産することは不可能であると考えられた。従って寒天の添加量としては0.3〜2w/w%が好ましく、更に0.5〜1.5 w/w%がより好ましいと考えられる。 Example 6 was relatively less effective in reducing bitterness. The reason for this was thought to be that this gel was soft and easily collapsed in the mouth, and there was little synergistic effect between agar and cacao powder. On the contrary, the gel of Example 8 with a large amount of agar added was very hard as shown in FIG. 1, and although the bitterness reduction effect was sufficiently confirmed from the questionnaire results, the feeling of administration was very bad. Moreover, the viscosity at the time of manufacture was very high, and it was thought that mass production was impossible. Therefore, the amount of agar added is preferably 0.3 to 2 w / w%, and more preferably 0.5 to 1.5 w / w%.
[試験例3](溶出試験;他のゲル化剤との比較)
実施例1及び対照例2〜対照例6より得られたゼリー製剤からのイソソルビドの溶出性を、日本薬局方 溶出試験法 パドル法にて試験した。ただし、試験液には、水、日本薬局方 崩壊試験法 第1液及び第2液900mLを用いて、パドル回転数は50rpmとした。また、ゼリー製剤は、咀嚼を考慮して約2mm径の大きさに粉砕して投入した。なお、定量はHPLC法により行った。寒天を用いたゼリー製剤と他のゲル化剤を用いて作製したゼリー製剤からのイソソルビドの溶出性の比較を図2〜図4に、また、図5には実施例1及び各対照例の15分後の溶出率をまとめて示した。[Test Example 3] (Dissolution test; comparison with other gelling agents)
The dissolution properties of isosorbide from the jelly preparations obtained from Example 1 and Control Examples 2 to 6 were tested by the Japanese Pharmacopoeia Dissolution Test Method Paddle Method. However, water, 900 mL of the Japanese Pharmacopoeia Disintegration Test Method 1st solution and 2nd solution were used as the test solution, and the paddle rotation speed was 50 rpm. Moreover, the jelly preparation was pulverized into a size of about 2 mm in consideration of mastication and then charged. The quantification was performed by the HPLC method. A comparison of the dissolution properties of isosorbide from a jelly preparation using agar and a jelly preparation prepared using another gelling agent is shown in FIGS. 2 to 4, and FIG. The elution rate after minutes was shown together.
ゲル化剤として寒天を用いたゼリー製剤である実施例1のみが、水、第1液及び第2液のいずれの試験液においてもイソソルビドの速やかな溶出を示し、生体内の環境に依存しない速やかな溶出を示すことがわかった。尚、各対照例に使用される各ゲル化剤の添加量は一般的に用いられる量であり、対照例で得られたゼリー製剤の硬さは実施例1と同等か又は柔らかいため、本試験は、対照例に不利な条件での比較ではない。 Only Example 1, which is a jelly preparation using agar as a gelling agent, showed rapid elution of isosorbide in any of the test solutions of water, the first solution and the second solution, and did not depend on the in vivo environment. It was found that it showed a proper elution. The amount of each gelling agent used in each control example is a commonly used amount, and the hardness of the jelly preparation obtained in the control example is the same as or softer than that in Example 1, so this test Is not a comparison under conditions unfavorable to the control.
[試験例4](溶出試験;カカオ末等の影響)
実施例1及び実施例2のゼリー製剤からのイソソルビドの溶出性試験を、試験例3と同様の方法により行った。試験結果の代表例を図6に示す。カカオ末及びその他の添加剤は、寒天を用いたゼリー製剤からのイソソルビドの溶出に影響せず、実施例1,2ともに、イソソルビドはゼリー製剤から速やかに溶出した。なお、その他のゲル化剤を用いて作製したゼリー製剤に関しても、カカオ末及びその他の添加剤はイソソルビドの溶出に影響しなかった。[Test Example 4] (Elution test; influence of cacao powder, etc.)
The dissolution test of isosorbide from the jelly preparations of Example 1 and Example 2 was performed in the same manner as in Test Example 3. A representative example of the test results is shown in FIG. The cacao powder and other additives did not affect the elution of isosorbide from the jelly preparation using agar, and in both Examples 1 and 2, isosorbide quickly eluted from the jelly preparation. Regarding jelly preparations prepared using other gelling agents, cacao powder and other additives did not affect the elution of isosorbide.
[試験例5](溶出試験;寒天量の影響)
実施例1及び実施例6 〜実施例8のゼリー製剤からのイソソルビドの溶出性試験を、試験例3と同様の方法により行った。試験結果を図7〜図9に示す。ゼリー製剤からのイソソルビドの溶出は寒天の添加量により大きくは影響されないが、添加量が極めて多いと若干溶出の遅延を示した。[Test Example 5] (Dissolution test; influence of agar amount)
The dissolution test of isosorbide from the jelly preparations of Example 1 and Example 6 to Example 8 was performed in the same manner as in Test Example 3. The test results are shown in FIGS. The elution of isosorbide from the jelly preparation was not greatly affected by the amount of agar added, but a slight delay was observed when the amount added was extremely large.
[試験例6](溶出試験;混合ゲル化系)
実施例1、実施例3〜実施例5のゼリー製剤からのイソソルビドの溶出性試験を、試験例5と同様の方法により行った。試験結果を図10〜図12に示す。ゲル化剤として寒天を用いたイソソルビド含有ゼリー製剤においては、更にその他のゲル化剤を添加しても、イソソルビドの速やかな溶出特性を維持していた。[Test Example 6] (Elution test; mixed gelation system)
The dissolution test of isosorbide from the jelly preparations of Example 1 and Examples 3 to 5 was performed in the same manner as in Test Example 5. The test results are shown in FIGS. In the isosorbide-containing jelly preparation using agar as the gelling agent, the rapid dissolution characteristics of isosorbide were maintained even when other gelling agents were added.
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JP4972311B2 (en) * | 2004-12-15 | 2012-07-11 | あすか製薬株式会社 | Oral preparation with reduced bitter taste of isosorbide and method for producing the same |
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WO2008084533A1 (en) * | 2007-01-10 | 2008-07-17 | Kowa Co., Ltd. | Therapeutic agent for meniere’s disease |
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AU2008262870B2 (en) | 2007-06-13 | 2013-07-11 | Otsuka Pharmaceutical Co., Ltd. | Equol-containing extract, method for production thereof, method for extraction of equol, and equol-containing food |
WO2010150400A1 (en) * | 2009-06-26 | 2010-12-29 | 日医工株式会社 | Jelly preparation containing isosorbide |
WO2012099082A1 (en) * | 2011-01-17 | 2012-07-26 | 味の素株式会社 | Branched-chain amino acid-containing jelly |
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