JP2012036167A - Oral liquid medicine - Google Patents
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- JP2012036167A JP2012036167A JP2011134112A JP2011134112A JP2012036167A JP 2012036167 A JP2012036167 A JP 2012036167A JP 2011134112 A JP2011134112 A JP 2011134112A JP 2011134112 A JP2011134112 A JP 2011134112A JP 2012036167 A JP2012036167 A JP 2012036167A
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- sumatriptan
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- 239000007788 liquid Substances 0.000 title abstract description 19
- 239000003814 drug Substances 0.000 title abstract description 5
- KQKPFRSPSRPDEB-UHFFFAOYSA-N sumatriptan Chemical compound CNS(=O)(=O)CC1=CC=C2NC=C(CCN(C)C)C2=C1 KQKPFRSPSRPDEB-UHFFFAOYSA-N 0.000 claims abstract description 43
- 229960003708 sumatriptan Drugs 0.000 claims abstract description 41
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims abstract description 39
- 150000003839 salts Chemical class 0.000 claims abstract description 30
- ZTHYODDOHIVTJV-UHFFFAOYSA-N Propyl gallate Chemical compound CCCOC(=O)C1=CC(O)=C(O)C(O)=C1 ZTHYODDOHIVTJV-UHFFFAOYSA-N 0.000 claims abstract description 18
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 claims abstract description 16
- 235000015165 citric acid Nutrition 0.000 claims abstract description 13
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 claims abstract description 10
- 229960001484 edetic acid Drugs 0.000 claims abstract description 10
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 claims abstract description 9
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 claims abstract description 9
- 239000003963 antioxidant agent Substances 0.000 claims abstract description 9
- 239000001630 malic acid Substances 0.000 claims abstract description 9
- 235000011090 malic acid Nutrition 0.000 claims abstract description 9
- 239000000473 propyl gallate Substances 0.000 claims abstract description 9
- 229940075579 propyl gallate Drugs 0.000 claims abstract description 9
- 235000010388 propyl gallate Nutrition 0.000 claims abstract description 9
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims abstract description 8
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 claims abstract description 8
- 230000007423 decrease Effects 0.000 claims abstract description 8
- 239000004310 lactic acid Substances 0.000 claims abstract description 8
- 235000014655 lactic acid Nutrition 0.000 claims abstract description 8
- 239000011975 tartaric acid Substances 0.000 claims abstract description 8
- 235000002906 tartaric acid Nutrition 0.000 claims abstract description 8
- 238000002156 mixing Methods 0.000 claims abstract description 3
- 235000002639 sodium chloride Nutrition 0.000 claims description 27
- 230000003078 antioxidant effect Effects 0.000 abstract description 3
- 238000002360 preparation method Methods 0.000 description 15
- 235000006708 antioxidants Nutrition 0.000 description 6
- 230000000052 comparative effect Effects 0.000 description 6
- 229940100688 oral solution Drugs 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 238000009472 formulation Methods 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- 208000019695 Migraine disease Diseases 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 206010027599 migraine Diseases 0.000 description 3
- 150000007524 organic acids Chemical class 0.000 description 3
- 239000008213 purified water Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- ZGTMUACCHSMWAC-UHFFFAOYSA-L EDTA disodium salt (anhydrous) Chemical compound [Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O ZGTMUACCHSMWAC-UHFFFAOYSA-L 0.000 description 2
- NIPNSKYNPDTRPC-UHFFFAOYSA-N N-[2-oxo-2-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(CNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 NIPNSKYNPDTRPC-UHFFFAOYSA-N 0.000 description 2
- AFCARXCZXQIEQB-UHFFFAOYSA-N N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(CCNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 AFCARXCZXQIEQB-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 230000037406 food intake Effects 0.000 description 2
- LNTHITQWFMADLM-UHFFFAOYSA-N gallic acid Chemical compound OC(=O)C1=CC(O)=C(O)C(O)=C1 LNTHITQWFMADLM-UHFFFAOYSA-N 0.000 description 2
- 230000001771 impaired effect Effects 0.000 description 2
- 239000006193 liquid solution Substances 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
- ZISSAWUMDACLOM-UHFFFAOYSA-N triptane Chemical compound CC(C)C(C)(C)C ZISSAWUMDACLOM-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical class NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- RXDLGFMMQFNVLI-UHFFFAOYSA-N [Na].[Na].[Ca] Chemical compound [Na].[Na].[Ca] RXDLGFMMQFNVLI-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000010411 cooking Methods 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical class OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 229940009662 edetate Drugs 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 235000004515 gallic acid Nutrition 0.000 description 1
- 229940074391 gallic acid Drugs 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 239000012676 herbal extract Substances 0.000 description 1
- 241000411851 herbal medicine Species 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 239000007923 nasal drop Substances 0.000 description 1
- 229940100662 nasal drops Drugs 0.000 description 1
- 229940100656 nasal solution Drugs 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000000018 receptor agonist Substances 0.000 description 1
- 229940044601 receptor agonist Drugs 0.000 description 1
- 229940037001 sodium edetate Drugs 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
Abstract
Description
本発明は、スマトリプタン又はその薬理上許容される塩を配合してなる内服液剤に関する。さらに詳しくはスマトリプタン又はその薬理上許容される塩と、クエン酸、リンゴ酸、酒石酸、乳酸及びこれらの塩からなる群から選ばれる一種以上の酸味料、さらにエデト酸及びこれらの塩並びに没食子酸プロピルからなる群から選ばれる一種以上の抗酸化剤を配合した内服液剤に関する。 The present invention relates to an internal liquid preparation comprising sumatriptan or a pharmacologically acceptable salt thereof. More specifically, sumatriptan or a pharmacologically acceptable salt thereof, one or more acidulants selected from the group consisting of citric acid, malic acid, tartaric acid, lactic acid and salts thereof, edetic acid and salts thereof, and gallic acid The present invention relates to an internal solution containing one or more antioxidants selected from the group consisting of propyl.
スマトリプタンとは、トリプタン系のセロトニン−１（５−ＨＴ１）受容体作動薬であって、片頭痛の治療に優れた効果を示す。 Sumatriptan is a triptan-based serotonin-1 (5-HT1) receptor agonist and exhibits excellent effects in the treatment of migraine.
現在までに、スマトリプタンは、錠剤、点鼻剤、注射剤などとして提供されているが（非特許文献１〜３）、内服液剤としては提供されていなかった。そこで、片頭痛の特性上、携帯が可能であり、かつ服用が容易であるスマトリプタンを配合した内服液剤が求められている。 To date, sumatriptan has been provided as tablets, nasal drops, injections, and the like (Non-Patent Documents 1 to 3), but has not been provided as an internal solution. Therefore, there is a need for an internal liquid preparation containing sumatriptan that is portable and easy to take due to the characteristics of migraine.
一方、内服液剤には、服用性向上の観点から、クエン酸又はその塩、リンゴ酸又はその塩などが配合されており、これら酸味料の添加が必要である。 On the other hand, citric acid or a salt thereof, malic acid or a salt thereof, and the like are blended in the internal liquid preparation from the viewpoint of improving the ingestibility, and it is necessary to add these acidulants.
本発明者らは、スマトリプタンとクエン酸などの酸味料を配合した内服液剤は、経時的にスマトリプタンの安定性が低下することを確認した。
よって、本発明はクエン酸、リンゴ酸、酒石酸、乳酸及びこれらの塩からなる群から選ばれる一種以上の酸味料を配合したスマトリプタン含有内服液剤において、生じたスマトリプタンの安定性の低下を抑制することを課題とする。
The inventors of the present invention confirmed that the stability of sumatriptan decreases over time with an oral solution containing sumatriptan and an acidulant such as citric acid.
Therefore, the present invention suppresses a decrease in the stability of the resulting sumatriptan in a sumatriptan-containing oral solution containing one or more acidulants selected from the group consisting of citric acid, malic acid, tartaric acid, lactic acid and salts thereof. The task is to do.
本発明者らは、上記課題を解決すべく鋭意検討を重ねた結果、酸味料を配合したスマトリプタン含有内服液剤に、エデト酸及びこれらの塩並びに没食子酸プロピルのような抗酸化剤を配合することにより、スマトリプタンの安定性の低下を抑制できることを見出し、本発明を完成するに至った。 As a result of intensive studies to solve the above-mentioned problems, the inventors of the present invention incorporate an antioxidant such as edetic acid and salts thereof and propyl gallate with a sumatriptan-containing internal liquid containing an acidulant. As a result, it was found that a decrease in the stability of sumatriptan can be suppressed, and the present invention has been completed.
即ち本発明は
（１）スマトリプタン又はその薬理上許容される塩と、クエン酸、リンゴ酸、酒石酸、乳酸及
びこれらの塩からなる群から選ばれる一種以上の酸味料、さらにエデト酸及びこれらの塩並びに没食子酸プロピルからなる群から選ばれる一種以上の抗酸化剤を配合したことを特徴とする内服液剤、
（２）スマトリプタン又はその薬理上許容される塩と、クエン酸、リンゴ酸、酒石酸、乳酸及びこれらの塩からなる群から選ばれる一種以上の酸味料を含有する内服液剤において、スマトリプタンの安定性の低下を、エデト酸及びこれらの塩並びに没食子酸プロピルからなる群から選ばれる一種以上の抗酸化剤を配合したことにより抑制する方法、
である。
That is, the present invention relates to (1) one or more acidulants selected from the group consisting of (1) sumatriptan or pharmacologically acceptable salts thereof, citric acid, malic acid, tartaric acid, lactic acid, and salts thereof, edetic acid, and these A liquid preparation containing one or more antioxidants selected from the group consisting of salt and propyl gallate,
(2) Sumatriptan stability in an oral solution containing sumatriptan or a pharmacologically acceptable salt thereof and one or more acidulants selected from the group consisting of citric acid, malic acid, tartaric acid, lactic acid and salts thereof A method of suppressing the decrease in property by blending one or more antioxidants selected from the group consisting of edetic acid and salts thereof and propyl gallate,
It is.
本発明により、スマトリプタンと酸味料を配合した内服液剤において、スマトリプタンの安定性の低下を抑制することができた。 According to the present invention, it was possible to suppress a decrease in the stability of sumatriptan in an oral solution containing sumatriptan and a sour agent.
本発明におけるスマトリプタンとは、片頭痛治療剤の３−[２−（ジメチルアミノ）エチル]−Ｎ−メチルインドール−５−メタンスルホンアミド）のことである。 Sumatriptan in the present invention is a migraine treatment agent 3- [2- (dimethylamino) ethyl] -N-methylindole-5-methanesulfonamide).
本発明における薬理上許容される塩とは、酢酸塩、カルシウム塩、クエン酸塩、ジエタ
ノールアミン塩、臭化水素酸塩、塩酸塩、リジン塩、カリウム塩、ナトリウム塩、コハク
酸塩、安息香酸塩などを挙げることができる。
The pharmacologically acceptable salt in the present invention is acetate, calcium salt, citrate, diethanolamine salt, hydrobromide, hydrochloride, lysine salt, potassium salt, sodium salt, succinate, benzoate. And so on.
本発明におけるスマトリプタン又はその薬理上許容される塩の含有（配合）量は、個々の患者にとって最も適切なものが何であるかによって、医者又は当業者等により決定されうる。この量は、治療される特定の患者の年齢、性別によって変わる可能性がある。しかしながら、０．０１ｍｇ／ｍＬ〜２０ｍｇ／ｍＬの範囲でスマトリプタン又はその薬理上許容される塩を含有することが好ましい。 The content (formulation) of sumatriptan or a pharmacologically acceptable salt thereof in the present invention can be determined by a doctor or a person skilled in the art depending on what is most appropriate for an individual patient. This amount may vary depending on the age and sex of the particular patient being treated. However, it is preferable to contain sumatriptan or a pharmacologically acceptable salt thereof in the range of 0.01 mg / mL to 20 mg / mL.
本発明に使用する酸味料とは、食品加工や調理において酸味を与えるために使われる物質で、各種の有機酸やその塩を指す。例えば、クエン酸、リンゴ酸、酒石酸、乳酸が挙げられ、好ましくはクエン酸である。 The acidulant used in the present invention is a substance used to give acidity in food processing and cooking, and refers to various organic acids and salts thereof. For example, citric acid, malic acid, tartaric acid and lactic acid can be mentioned, and citric acid is preferred.
本発明に使用する没食子酸プロピルの含有（配合）量は、スマトリプタンと酸味料を配合した内服液剤中において生じるスマトリプタンの安定性の低下を抑制する効果を有する範囲であれば特に制限はされないが、好ましくはスマトリプタン１質量部に対して、０．０２質量部以上である。 The content (formulation) of propyl gallate used in the present invention is not particularly limited as long as it has an effect of suppressing a reduction in the stability of sumatriptan produced in an internal liquid preparation containing sumatriptan and a sour agent. However, Preferably it is 0.02 mass part or more with respect to 1 mass part of sumatriptan.
本発明に使用するエデト酸又はその塩としては、例えばエデト酸二ナトリウムやエデト酸カルシウム二ナトリウムが挙げられる。
なお、本発明のエデト酸又はその塩の含有（配合）量は、スマトリプタンと酸味料を配合した内服液剤中において生じるスマトリプタンの安定性の低下を抑制する効果を有する範囲であれば特に制限はされないが、好ましくはスマトリプタン１質量部に対して、０．０２質量部以上である。
Examples of edetic acid or a salt thereof used in the present invention include disodium edetate and disodium calcium edetate.
Note that the content (formulation) of edetic acid or a salt thereof of the present invention is particularly limited as long as it has an effect of suppressing a decrease in the stability of sumatriptan produced in an internal liquid preparation containing sumatriptan and a sour agent. However, it is preferably 0.02 parts by mass or more per 1 part by mass of sumatriptan.
本発明の内服液剤の好ましいｐＨは２．５〜７．０であり、さらに好ましくは２．５〜５．０であり、もっとも好ましくは２．５〜４．０である。ｐＨが２．５未満であると、酸味が強すぎて服用性の点で好ましくなく、ｐＨが７．０を超える領域でも、服用性の点で好ましくないからである。ｐＨの調整には、例えば、酢酸などの有機酸又は有機酸の塩、リン酸、塩酸などの無機酸、水酸化ナトリウム、水酸化カリウムなどの無機塩基を用いることができる。 The preferred pH of the internal liquid preparation of the present invention is 2.5 to 7.0, more preferably 2.5 to 5.0, and most preferably 2.5 to 4.0. This is because if the pH is less than 2.5, the acidity is so strong that it is not preferable in terms of ingestion, and even if the pH exceeds 7.0, it is not preferable in terms of ingestion. For adjusting the pH, for example, an organic acid such as acetic acid or a salt of the organic acid, an inorganic acid such as phosphoric acid or hydrochloric acid, or an inorganic base such as sodium hydroxide or potassium hydroxide can be used.
本発明の内服液剤には、ビタミン類、ミネラル類、生薬、生薬抽出物などを本発明の効果を損なわない範囲で適宜に配合できる。また、必要に応じて着色剤、香料、界面活性剤、溶解補助剤、保存剤などの添加物を本発明の効果を損なわない範囲で適宜に配合できる。これらの添加物等は、１種で単独に配合しても、２種以上を適宜組み合わせて配合してもよい。 Vitamins, minerals, herbal medicines, herbal extracts and the like can be appropriately added to the internal liquid preparation of the present invention as long as the effects of the present invention are not impaired. In addition, additives such as a colorant, a fragrance, a surfactant, a solubilizing agent, and a preservative can be appropriately blended as necessary so long as the effects of the present invention are not impaired. These additives and the like may be blended singly or in combination of two or more.
本発明の内服液剤は、常法により調製することができ、その方法は特に限定されるものではない。通常、各成分を適量の精製水で溶解した後、ｐＨ及び容量を、残りの精製水を加えて調整し、必要に応じてろ過、殺菌処理することにより得られる。 The internal liquid preparation of the present invention can be prepared by a conventional method, and the method is not particularly limited. Usually, after each component is dissolved with an appropriate amount of purified water, the pH and volume are adjusted by adding the remaining purified water, followed by filtration and sterilization as necessary.
本発明の内服液剤は、例えばシロップ剤、ドリンク剤などの医薬品や医薬部外品などとして提供することができる。 The internal liquid preparation of the present invention can be provided as pharmaceuticals such as syrups and drinks, quasi drugs and the like.
以下に、実施例、比較例及び試験例を挙げ、本発明をさらに詳細に説明するが、本発明はこれらの実施例等に何ら限定されるものではない。 Hereinafter, the present invention will be described in more detail with reference to Examples, Comparative Examples, and Test Examples, but the present invention is not limited to these Examples.
（１）各内服液剤の調製
表１に記載の処方の各成分を秤量して、精製水に溶解させ、ｐＨを３．０になるよう、かつ、内服液剤の全量が１０ｍＬとなるよう調整した。その後にガラス瓶に充填し、キャップを施して本発明の実施例１−２及び比較例１−３の内服液剤を得た。
(1) Preparation of each internal liquid solution Each component of the formulation described in Table 1 was weighed and dissolved in purified water, and adjusted so that the pH was 3.0 and the total amount of the internal liquid solution was 10 mL. . Then, it filled into the glass bottle, the cap was given, and the internal use liquid agent of Example 1-2 of this invention and Comparative Example 1-3 was obtained.
（２）試験方法
表１の実施例１−２及び比較例１−３で示す組成のスマトリプタン含有内服液剤を６５℃の恒温槽中で１４日間保存し、内服液剤中のスマトリプタン含有量をＨＰＬＣで測定した。スマトリプタンを溶解させた直後の内服液剤中のスマトリプタン含有量に対して、６５℃、１４日間保存後の内服液剤中のスマトリプタン含有量（残存率）を計算した。結果を表１に示す。
(2) Test method A sumatriptan-containing internal liquid preparation having the composition shown in Example 1-2 of Table 1 and Comparative Example 1-3 was stored in a thermostatic bath at 65 ° C. for 14 days, and the sumatriptan content in the internal liquid preparation was determined. Measured by HPLC. The sumatriptan content (residual rate) in the internal solution after storage at 65 ° C. for 14 days was calculated with respect to the sumatriptan content in the internal solution immediately after dissolving the sumatriptan. The results are shown in Table 1.
（３）結果
比較例１の結果から、クエン酸を配合したスマトリプタン配合内服液剤は、６５℃、１４日間保存後の内服液剤中のスマトリプタンの残存率が低くなることが分かった。しかし、没食子酸プロピルまたはエデト酸ナトリウムを用いた実施例１、２では、クエン酸を配合しているにも関わらず、内服液剤中のスマトリプタンの残存率の低下が抑制されることが分かった。
(3) Results From the results of Comparative Example 1, it was found that the sumatriptan-containing internal liquid preparation containing citric acid had a low residual ratio of sumatriptan in the internal liquid preparation after storage at 65 ° C. for 14 days. However, in Examples 1 and 2 using propyl gallate or sodium edetate, it was found that the reduction of the residual ratio of sumatriptan in the oral solution was suppressed despite the addition of citric acid. .
なお、比較例２、３に示したとおり、没食子酸プロピル、エデト酸以外の抗酸化剤であるアスコルビン酸または亜硫酸ナトリウムを配合した場合は、比較例１と比較してほぼ変更がないか、あるいはさらに低下することが分かった。即ち、全ての抗酸化剤で内服液剤中のスマトリプタンの安定性を抑制出来るわけではないことが分かった。 As shown in Comparative Examples 2 and 3, when ascorbic acid or sodium sulfite, which is an antioxidant other than propyl gallate and edetic acid, was blended, there was almost no change compared to Comparative Example 1, or It turned out that it fell further. That is, it has been found that not all antioxidants can suppress the stability of sumatriptan in the oral solution.
本発明により、長期に保存可能なスマトリプタン含有内服液剤を製造することが可能となったので、商品性の高いスマトリプタン含有内服液剤を医薬品や医薬部外品などの分野で提供することが期待される。 According to the present invention, it has become possible to produce a sumatriptan-containing internal solution that can be stored for a long period of time. Is done.
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| US20070166336A1 (en) * | 2005-12-13 | 2007-07-19 | David Delmarre | Stable and palatable oral liquid sumatriptan compositions |
| WO2009014960A1 (en) * | 2007-07-23 | 2009-01-29 | Teikoku Pharma Usa, Inc. | Organoleptically acceptable indole serotonin receptor agonist oral dosage formulations and methods of using the same |
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| WO2009014960A1 (en) * | 2007-07-23 | 2009-01-29 | Teikoku Pharma Usa, Inc. | Organoleptically acceptable indole serotonin receptor agonist oral dosage formulations and methods of using the same |
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| RU2762725C2 (en) * | 2009-09-25 | 2021-12-22 | Д-Р Редди'С Лабораторис Лтд. | Compositions containing triptane compounds |
| WO2020074463A1 (en) * | 2018-10-09 | 2020-04-16 | Aziende Chimiche Riunite Angelini Francesco - A.C.R.A.F. S.P.A. | Oral liquid composition comprising triptan |
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