JP2554784B2 - Suspension syrup - Google Patents
Suspension syrupInfo
- Publication number
- JP2554784B2 JP2554784B2 JP3051603A JP5160391A JP2554784B2 JP 2554784 B2 JP2554784 B2 JP 2554784B2 JP 3051603 A JP3051603 A JP 3051603A JP 5160391 A JP5160391 A JP 5160391A JP 2554784 B2 JP2554784 B2 JP 2554784B2
- Authority
- JP
- Japan
- Prior art keywords
- carbocysteine
- suspension
- syrup
- added
- cellulose
- 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.)
- Expired - Lifetime
Links
- 239000000725 suspension Substances 0.000 title claims description 25
- 239000006188 syrup Substances 0.000 title claims description 17
- 235000020357 syrup Nutrition 0.000 title claims description 17
- GBFLZEXEOZUWRN-VKHMYHEASA-N S-carboxymethyl-L-cysteine Chemical compound OC(=O)[C@@H](N)CSCC(O)=O GBFLZEXEOZUWRN-VKHMYHEASA-N 0.000 claims description 44
- 229960004399 carbocisteine Drugs 0.000 claims description 44
- 239000002245 particle Substances 0.000 claims description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 12
- 239000002270 dispersing agent Substances 0.000 claims description 10
- 239000013078 crystal Substances 0.000 claims description 9
- 229920002134 Carboxymethyl cellulose Polymers 0.000 claims description 4
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 4
- 235000010948 carboxy methyl cellulose Nutrition 0.000 claims description 4
- 239000008112 carboxymethyl-cellulose Substances 0.000 claims description 4
- 239000001913 cellulose Substances 0.000 claims description 4
- 229920006184 cellulose methylcellulose Polymers 0.000 claims description 3
- 229920000609 methyl cellulose Polymers 0.000 claims description 3
- 239000001923 methylcellulose Substances 0.000 claims description 3
- 235000010981 methylcellulose Nutrition 0.000 claims description 3
- 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 claims description 2
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 2
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 2
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 2
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 claims description 2
- 238000010298 pulverizing process Methods 0.000 claims description 2
- 239000000661 sodium alginate Substances 0.000 claims description 2
- 235000010413 sodium alginate Nutrition 0.000 claims description 2
- 229940005550 sodium alginate Drugs 0.000 claims description 2
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 claims 1
- 239000004354 Hydroxyethyl cellulose Substances 0.000 claims 1
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 claims 1
- 239000000843 powder Substances 0.000 description 8
- 239000000203 mixture Substances 0.000 description 7
- 235000003599 food sweetener Nutrition 0.000 description 6
- 238000000034 method Methods 0.000 description 6
- 239000003765 sweetening agent Substances 0.000 description 6
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 239000003205 fragrance Substances 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 239000008213 purified water Substances 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 239000003086 colorant Substances 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 239000008187 granular material Substances 0.000 description 3
- 210000003097 mucus Anatomy 0.000 description 3
- 239000000375 suspending agent Substances 0.000 description 3
- 239000005711 Benzoic acid Substances 0.000 description 2
- 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 2
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
- 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 2
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- 235000010233 benzoic acid Nutrition 0.000 description 2
- 239000006185 dispersion Substances 0.000 description 2
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 2
- 239000010419 fine particle Substances 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 2
- 239000011259 mixed solution Substances 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 230000002335 preservative effect Effects 0.000 description 2
- 235000010199 sorbic acid Nutrition 0.000 description 2
- 239000004334 sorbic acid Substances 0.000 description 2
- 229940075582 sorbic acid Drugs 0.000 description 2
- 229960002920 sorbitol Drugs 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 150000005846 sugar alcohols Chemical class 0.000 description 2
- 239000000811 xylitol Substances 0.000 description 2
- 235000010447 xylitol Nutrition 0.000 description 2
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 2
- 229960002675 xylitol Drugs 0.000 description 2
- SHZGCJCMOBCMKK-UHFFFAOYSA-N D-mannomethylose Natural products CC1OC(O)C(O)C(O)C1O SHZGCJCMOBCMKK-UHFFFAOYSA-N 0.000 description 1
- 239000004287 Dehydroacetic acid Substances 0.000 description 1
- PNNNRSAQSRJVSB-SLPGGIOYSA-N Fucose Natural products C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C=O PNNNRSAQSRJVSB-SLPGGIOYSA-N 0.000 description 1
- SHZGCJCMOBCMKK-DHVFOXMCSA-N L-fucopyranose Chemical compound C[C@@H]1OC(O)[C@@H](O)[C@H](O)[C@@H]1O SHZGCJCMOBCMKK-DHVFOXMCSA-N 0.000 description 1
- 206010036790 Productive cough Diseases 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000002421 anti-septic effect Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 229960004365 benzoic acid Drugs 0.000 description 1
- SQVRNKJHWKZAKO-UHFFFAOYSA-N beta-N-Acetyl-D-neuraminic acid Natural products CC(=O)NC1C(O)CC(O)(C(O)=O)OC1C(O)C(O)CO SQVRNKJHWKZAKO-UHFFFAOYSA-N 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 210000000254 ciliated cell Anatomy 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 235000019258 dehydroacetic acid Nutrition 0.000 description 1
- JEQRBTDTEKWZBW-UHFFFAOYSA-N dehydroacetic acid Chemical compound CC(=O)C1=C(O)OC(C)=CC1=O JEQRBTDTEKWZBW-UHFFFAOYSA-N 0.000 description 1
- 229940061632 dehydroacetic acid Drugs 0.000 description 1
- PGRHXDWITVMQBC-UHFFFAOYSA-N dehydroacetic acid Natural products CC(=O)C1C(=O)OC(C)=CC1=O PGRHXDWITVMQBC-UHFFFAOYSA-N 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 239000003925 fat Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- SQVRNKJHWKZAKO-OQPLDHBCSA-N sialic acid Chemical compound CC(=O)N[C@@H]1[C@@H](O)C[C@@](O)(C(O)=O)OC1[C@H](O)[C@H](O)CO SQVRNKJHWKZAKO-OQPLDHBCSA-N 0.000 description 1
- 235000002639 sodium chloride Nutrition 0.000 description 1
- 210000003802 sputum Anatomy 0.000 description 1
- 208000024794 sputum Diseases 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Description
【０００１】[0001]
【産業上の利用分野】本発明は気道粘液調整・粘膜正常
化剤であるカルボシステインを含有する懸濁シロップ剤
に関する。BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a suspension syrup containing carbocysteine, which is an airway mucus regulating / mucosal normalizing agent.
【０００２】[0002]
【従来の技術とその問題点】カルボシステインは公知の
医薬用化合物である。その薬理作用は気道粘液中のシア
ル酸及びフコースの構成比を正常化することにより、粘
液の粘度を低下させ、気管支粘膜上皮の線毛細胞を修復
し、痰の排出を促進する。2. Description of the Related Art Carbocysteine is a known pharmaceutical compound. Its pharmacological action normalizes the composition ratio of sialic acid and fucose in airway mucus, thereby lowering the viscosity of mucus, repairing ciliated cells of bronchial mucosal epithelium, and promoting sputum excretion.
【０００３】カルボシステインの製剤は、従来より経口
投与製剤として、錠剤（２５０ｍｇ）、細粒剤（０．５
％）、シロップ剤（５％）が開発され、医療の場に供さ
れている。しかし、カルボシステインの服用量は成人で
一回５００ｍｇと多く、錠剤の場合には大型錠剤とな
り、服用困難な場合があった。Conventionally, the preparation of carbocysteine has been used as an oral preparation, such as tablets (250 mg) and fine granules (0.5 mg).
%) And syrup (5%) have been developed and are being used in the medical field. However, the dose of carbocysteine was as large as 500 mg once for adults, and in the case of tablets, it became a large tablet, which was sometimes difficult to take.
【０００４】錠剤や細粒剤の服用の困難な患者に適する
経口投与剤形として、まず高濃度（１０ｗ／ｖ％以上）
のカルボシステイン水溶液が考えられた。しかし、カル
ボシステインの水に対する溶解度は１ｍｇ／ｍｌ以下と
低い。溶液状でカルボシステインを高濃度含有させるこ
とは、水酸化ナトリウムなどのアルカリ成分を高濃度に
加えれば達成できるが、結果として高濃度のカルボシス
テイン溶液は同時にアルカリ成分を大量に含み、かかる
製剤は医療に供せないものであった。さらに、高濃度の
カルボシステイン溶液は長期保存や光により着色変化や
分解物の生成などがあり、安定性の点で問題があった。As an oral dosage form suitable for patients who have difficulty in taking tablets and fine granules, first, high concentration (10 w / v% or more)
An aqueous solution of carbocysteine was considered. However, the solubility of carbocysteine in water is as low as 1 mg / ml or less. A high concentration of carbocysteine in solution can be achieved by adding a high concentration of an alkali component such as sodium hydroxide, but as a result, a high-concentration carbocysteine solution contains a large amount of alkali components at the same time, and such a formulation is It could not be used for medical treatment. Furthermore, the high-concentration carbocysteine solution has a problem in terms of stability because it is stored for a long period of time and changes in color due to light and decomposition products are generated.
【０００５】カルボシステインは、次に懸濁剤としての
開発が可能と考えられた。しかし、カルボシステインの
結晶は単に水中に分散しただけでは、容易に沈降し、懸
濁シロップ剤として提供することができない。また懸濁
剤に一般的に使用されている分散剤を用いることによ
り、結晶の沈降速度をある程度遅くすることはできた
が、長期間の保存で均一な懸濁状態を維持できなかっ
た。[0005] Carbocysteine was then considered to be possible to develop as a suspension. However, the crystals of carbocysteine are easily settled and cannot be provided as a suspension syrup simply by dispersing them in water. Moreover, although it was possible to slow down the settling rate of crystals to some extent by using a dispersant that is generally used as a suspending agent, it was not possible to maintain a uniform suspended state after long-term storage.
【０００６】このような問題から、高濃度のカルボシス
テインシロップ剤が望まれながら、開発されていなかっ
た。[0006] Due to these problems, a high-concentration carbocysteine syrup preparation has been desired but not developed.
【０００７】[0007]
【問題点を解決するための手段】以上の問題を解決する
ため、本発明者らは、カルボシステインを高濃度に含有
させることができる懸濁シロップ剤の開発について鋭意
研究した。その結果、カルボシステインを均一に分散さ
せた安定な懸濁液として完成し、本発明のカルボシステ
インを有効成分とする懸濁シロップ剤を創作するに至っ
た。すなわち、カルボシステインの結晶（平均粒子径４
５μｍ）を分散剤及び水と共に高圧ホモジナイザーで処
理すると、驚くべきことにカルボシステインの微粉化と
分散化が同時に行え、安定な懸濁剤として沈降を防止す
る方法を新たに見い出した。この処理により平均粒子径
４５μｍのカルボシステインの粒子径は１５μｍ以下に
まで微粉化し、分散安定な懸濁液を調製することができ
ることを見い出し、本発明を完成した。[Means for Solving the Problems] In order to solve the above problems, the present inventors have made extensive studies on the development of a suspension syrup capable of containing carbocysteine in a high concentration. As a result, a stable suspension in which carbocysteine was uniformly dispersed was completed, and a suspension syrup preparation containing the carbocysteine of the present invention as an active ingredient was created. That is, crystals of carbocysteine (average particle size 4
(5 μm) was treated with a high-pressure homogenizer together with a dispersant and water, and surprisingly, a new method was found to prevent carbocysteine from being finely powdered and dispersed at the same time to prevent precipitation as a stable suspending agent. By this treatment, it was found that carbocysteine having an average particle diameter of 45 μm can be finely pulverized to a particle diameter of 15 μm or less to prepare a dispersion stable suspension, and the present invention was completed.
【０００８】結晶を微粉化する従来の方法は、各種粉砕
機を使用する多様な方法がある。例えば、乾式で行うジ
ェットミル、ボールミル、ローラーミル等を使用して、
粒子を微粉化することができる。カルボシステインもジ
ェットミルで粉砕し、平均粒子径１５μｍ以下の微粉末
を得ることができる。通常、懸濁液は、このように微粉
化した薬物に分散剤及び水を加えて撹拌して製する。し
かし、カルボシステインの微粉末はこの方法では安定な
懸濁液を製することができなかった（表−１）。そこ
で、カルボシステインの懸濁安定なシロップ剤を得るた
め、本発明者らは鋭意研究した。その結果、カルボシス
テインの結晶（平均粒子径４５μｍ）に分散剤及び水を
加えて撹拌した混合液を、高圧ホモジナイザーで処理す
る方法を新たに見い出した。この方法によれば、原末粒
子径４５μｍを有するカルボシステインを１５μｍ以下
の微粒子に微粉化できるばかりでなく、分散剤と同時に
処理することにより、安定な懸濁剤を得ることができる
特徴を有する（表１参照）。There are various conventional methods for pulverizing crystals, which use various crushers. For example, using a dry jet mill, ball mill, roller mill, etc.,
The particles can be micronized. Carbocysteine can also be ground by a jet mill to obtain a fine powder having an average particle size of 15 μm or less. Generally, a suspension is prepared by adding a dispersant and water to the drug thus pulverized and stirring the mixture. However, the fine powder of carbocysteine could not produce a stable suspension by this method (Table-1). Therefore, the inventors of the present invention have conducted diligent studies in order to obtain a suspension stable syrup of carbocysteine. As a result, a new method of treating a mixed solution of a carbocysteine crystal (average particle diameter 45 μm) with a dispersant and water added thereto and stirring with a high-pressure homogenizer was newly found. According to this method, not only can carbocysteine having a bulk powder particle size of 45 μm be finely divided into fine particles of 15 μm or less, but a stable suspending agent can be obtained by treating it simultaneously with a dispersant. (See Table 1).
【０００９】[0009]
【表１】 [Table 1]
【００１０】カルボシステインの懸濁シロップ剤の調製
法として、高圧ホモジナイザーは最適であった。高圧ホ
モジナイザーは、一般には牛乳等の油脂を乳化する装置
として用いられているが、結晶粉末の微粉化装置として
用いられた例はなかった。本発明者らは、鋭意研究した
結果、カルボシステインのような結晶性粉末でも、高圧
ホモジナイザーで処理することにより微粉化することが
でき、しかも、分散安定化に有効であることを見い出し
た。The high-pressure homogenizer was the most suitable method for preparing a suspension syrup of carbocysteine. The high-pressure homogenizer is generally used as a device for emulsifying fats and oils such as milk, but there has been no case where it is used as a device for atomizing crystal powder. As a result of intensive studies, the present inventors have found that even crystalline powder such as carbocysteine can be finely pulverized by treating with a high-pressure homogenizer and is effective for dispersion stabilization.
【００１１】市販の高圧ホモジナイザーの装置として、
ゴーリンホモジナイザー（ゴーリン社製、１５ＭＲ−８
Ｔ型）やマイクロフルイダイザー（マイクロフルイディ
スク社製、Ｍ−１１０−Ｔ型）などがある。このような
高圧ホモジナイザーを使用して粉砕処理（圧力４００〜
１０００ｋｇ／ｃｍ2 ）を行ったとき、最適な微粉砕結
晶（平均粒子径１０μｍ）が得られた。カルボシステイ
ン原末（平均粒子径４５μｍ）を水に懸濁し、高圧ホモ
ジナイザーで処理することにより、平均粒子径１０μｍ
以下の微粉末を得ることができる。しかし、この微粉化
カルボシステイン懸濁液は安定性が悪く、再分散性に劣
るものであった。安定なカルボシステイン懸濁液を得る
ためには、カルボシステインの原末に分散剤を添加した
混合液を高圧ホモジナイザーで処理することが必要であ
ることを見い出し、本発明を完成させた。As a commercially available high-pressure homogenizer device,
Gorin homogenizer (Gorin Co., 15MR-8
T-type) and Microfluidizer (M-110-T type manufactured by Microfluidic Disc). A crushing process (pressure 400-
The optimum finely pulverized crystals (average particle size 10 μm) were obtained when 1000 kg / cm 2 ) was performed. Carbocysteine bulk powder (average particle size 45 μm) was suspended in water and treated with a high-pressure homogenizer to give an average particle size of 10 μm.
The following fine powder can be obtained. However, this micronized carbocysteine suspension had poor stability and poor redispersibility. In order to obtain a stable suspension of carbocysteine, it was found that it is necessary to treat a mixed solution of a bulk powder of carbocysteine added with a dispersant with a high-pressure homogenizer, and the present invention was completed.
【００１２】高圧ホモジナイザーで処理するときのカル
ボシステイン濃度は５〜３０ｗ／ｖ％が望ましい。The concentration of carbocysteine during treatment with a high pressure homogenizer is preferably 5 to 30 w / v%.
【００１３】好ましい分散剤としては、メチルセルロー
ス、結晶セルロース、カルボキシメチルセルロース及び
その塩、ヒドロキシプロピルメチルセルロース、アルギ
ン酸ナトリウム、及び結晶セルロース・カルボキシメチ
ルセルロース（アビセルＲＣ）などである。これらの分
散剤の添加量は、０．５〜５ｗ／ｖ％が望ましい。この
範囲の濃度であれば、微粒子の沈降が抑えられ、長期間
保存により一旦沈降した場合でも、容易に再分散が可能
であった。Preferred dispersants include methyl cellulose, crystalline cellulose, carboxymethyl cellulose and its salts, hydroxypropyl methyl cellulose, sodium alginate, crystalline cellulose / carboxymethyl cellulose (Avicel RC) and the like. The addition amount of these dispersants is preferably 0.5 to 5 w / v%. When the concentration is within this range, the fine particles are prevented from settling, and even if the particles once settled due to long-term storage, they can be easily redispersed.
【００１４】懸濁シロップ剤中のカルボシステイン濃度
は、５〜３０ｗ／ｖ％の範囲が望ましい。５ｗ／ｖ％以
下では服用時多容量となり不都合であり、３０ｗ／ｖ％
以上では結晶量が多く高粘度となり、流動性が低下し服
用することが困難となる。最も好ましいのは、５〜２０
ｗ／ｖ％である。The concentration of carbocysteine in the suspension syrup is preferably in the range of 5 to 30 w / v%. If the dose is 5 w / v% or less, it is inconvenient because of a large dose when ingested, 30 w / v%
In the above case, the amount of crystals is large and the viscosity is high, the fluidity is lowered and it becomes difficult to take the drug. Most preferred is 5 to 20
w / v%.
【００１５】カルボシステインを水に分散させた液は酸
味が強い。これに適当な甘味剤を加えることにより、服
用し易い味とすることができる。したがって、懸濁シロ
ップ剤として、服用しやすくするために甘味剤の添加が
望ましい。甘味剤としては、Ｄ−ソルビトール、キシリ
トールまたはＤ−マンニトール等の糖アルコールの使用
が最適である。糖アルコールの添加量は１０〜６０ｗ／
ｖ％であり、望ましくは２０〜４０ｗ／ｖ％添加する。
甘味剤として、これらの甘味剤を単独であるいは混合し
て用いることができる。また、合成甘味剤であるサッカ
リンナトリウムを加えて用いることもできる。The liquid in which carbocysteine is dispersed in water has a strong sourness. By adding an appropriate sweetener to this, the taste can be made easy to take. Therefore, as a suspension syrup, it is desirable to add a sweetener to make it easier to take. As a sweetener, the use of sugar alcohol such as D-sorbitol, xylitol or D-mannitol is most suitable. The amount of sugar alcohol added is 10 to 60 w /
v%, preferably 20-40 w / v%.
As the sweetener, these sweeteners can be used alone or in a mixture. Further, sodium saccharin, which is a synthetic sweetener, can be added and used.
【００１６】服用性を高めるために、香料を添加するこ
とは有効であり、香料としてフルーツエッセンスを微量
添加する。It is effective to add a fragrance to enhance the ingestability, and a small amount of fruit essence is added as a fragrance.
【００１７】防腐性を高めるために保存剤を添加するこ
とは有効であり、保存剤として、ソルビン酸、安息香
酸、デヒドロ酢酸またはパラオキシ安息香酸エステル類
を０．００５〜０．５ｗ／ｖ％添加する。望ましくは
０．０１〜０．２ｗ／ｖ％添加する。It is effective to add a preservative in order to enhance antiseptic properties, and 0.005 to 0.5 w / v% of sorbic acid, benzoic acid, dehydroacetic acid or paraoxybenzoic acid ester is added as a preservative. To do. Desirably, 0.01 to 0.2 w / v% is added.
【００１８】また、使用性を高めるために、着色剤の添
加も可能である。着色剤としては、医薬品に用いられる
ものであればいずれでも良い。A colorant may be added to improve usability. Any colorant may be used as long as it is used in medicine.
【００１９】カルボシステイン溶液では、室温に長期間
保存すると徐々に分解する。実施例１で得たカルボシス
テインの懸濁シロップ剤について、４０°で保存したと
きの安定性を試験し、その結果を表−２に示した。The carbocysteine solution gradually decomposes when stored at room temperature for a long time. The suspension of carbocisteine obtained in Example 1 was tested for stability when stored at 40 °. The results are shown in Table 2.
【００２０】[0020]
【表２】 [Table 2]
【００２１】これらの結果に基づき安定なカルボシステ
インの懸濁シロップ剤を完成させた。Based on these results, a stable carbocysteine suspension syrup was completed.
【００２２】[0022]
【効果】このようにして得られた本発明のカルボシステ
イン懸濁シロップ剤は、経口からの服用がしやすく、錠
剤や細粒剤の服用の困難な患者でも容易に服用でき、し
かも、高薬量のカルボシステインの服用も可能にした製
剤を提供できる。[Effect] The thus-obtained carbocisteine suspension syrup of the present invention is easy to take orally, and can be taken easily even by patients with difficulty in taking tablets and fine granules, and high drug It is possible to provide a formulation which enables the administration of an amount of carbocysteine.
【００２３】[0023]
【実施例】以下、実施例により、発明具体化の諸態様を
説明するが、例示は当然説明のものであって、発明を限
定するものではない。EXAMPLES Hereinafter, various modes of embodying the invention will be described with reference to examples, but the exemplification is of course merely an explanation and does not limit the invention.
【００２４】実施例１ カルボシステイン１００ｇ、結晶セルロース・カルボキ
シメチルセルロース（アビセルＲＣ）１０ｇ、ソルビン
酸１ｇに精製水５００ｍｌを加え、ホモジナイザーを用
いて分散した後、これをゴーリンホモジナイザー（１５
ＭＲ−８Ｔ型）を用いて６５０ｋｇ／ｃｍ2 の高圧処理
を行い、平均粒子径１０．０μｍの均一な懸濁液とし
た。これに、キシリトール４００ｇ及び香料を微量加え
て溶かし、精製水を加えて１０００ｍｌとし、カルボシ
ステイン懸濁シロップ剤を製した。 実施例２ カルボシステイン２００ｇ、メチルセルロース５０ｇに
精製水５００ｍｌを加え、ホモジナイザーを用いて分散
した後、これをマイクロフルイダイザー（Ｍ−１１０Ｔ
型）を用いて１０００ｋｇ／ｃｍ2 の高圧処理を行い、
平均粒子径１１．１μｍの均一な懸濁液とした。これ
に、Ｄ−ソルビトール４００ｇ、安息香酸０．５ｇ、香
料微量、着色剤微量を加えて溶かし、精製水を加えて１
０００ｍｌとし、カルボシステイン懸濁シロップ剤を製
した。Example 1 Carbocysteine (100 g), crystalline cellulose / carboxymethyl cellulose (Avicel RC) (10 g) and sorbic acid (1 g) were added to purified water (500 ml) and the mixture was dispersed using a homogenizer.
MR-8T type) was used to perform a high-pressure treatment of 650 kg / cm 2 to obtain a uniform suspension having an average particle diameter of 10.0 μm. To this, 400 g of xylitol and a slight amount of fragrance were added and dissolved, and purified water was added to 1000 ml to prepare a carbocysteine suspension syrup. Example 2 To 200 g of carbocysteine and 50 g of methyl cellulose, 500 ml of purified water was added, and the mixture was dispersed using a homogenizer, which was then mixed with a microfluidizer (M-110T).
Type) to perform high pressure treatment of 1000 kg / cm 2 ,
A uniform suspension having an average particle diameter of 11.1 μm was prepared. To this, 400 g of D-sorbitol, 0.5 g of benzoic acid, a trace amount of a fragrance and a trace amount of a coloring agent were added and dissolved, and purified water was added to 1
The volume was adjusted to 000 ml to prepare a carbocysteine suspension syrup.
Claims (2)
ｗ／ｖ％の分散剤と水と共に高圧ホモジナイザーを用い
て微粉化および分散化処理し、カルボシステインの平均
粒子径を１５μｍ以下に製することを特徴とするカルボ
システインを５〜３０ｗ／ｖ％含有の懸濁シロップ剤。1. A crystal of carbocysteine is added in an amount of 0.5-5.
Containing 5 to 30 w / v% of carbocysteine, which is characterized by producing an average particle size of carbocysteine to 15 μm or less by pulverizing and dispersing using a high pressure homogenizer together with a w / v% dispersant and water. Suspension syrup.
ロキシエチルセルロース、アルギン酸ナトリウム、結晶
セルロース・カルボキシメチルセルロースまたはヒドロ
キシプロピルメチルセルロースから選ばれた１種または
２種以上を含有することを特徴とする請求項１記載の懸
濁シロップ剤。2. The suspension according to claim 1, wherein the dispersant contains one or more selected from methyl cellulose, hydroxyethyl cellulose, sodium alginate, crystalline cellulose / carboxymethyl cellulose, and hydroxypropyl methyl cellulose. Cloudy syrup.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP3051603A JP2554784B2 (en) | 1991-03-15 | 1991-03-15 | Suspension syrup |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP3051603A JP2554784B2 (en) | 1991-03-15 | 1991-03-15 | Suspension syrup |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH04288013A JPH04288013A (en) | 1992-10-13 |
| JP2554784B2 true JP2554784B2 (en) | 1996-11-13 |
Family
ID=12891477
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP3051603A Expired - Lifetime JP2554784B2 (en) | 1991-03-15 | 1991-03-15 | Suspension syrup |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP2554784B2 (en) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0995435B1 (en) | 1997-05-14 | 2007-04-25 | Senju Pharmaceutical Co., Ltd. | Aqueous suspension preparations with excellent redispersibility |
| WO2000001727A1 (en) * | 1998-06-30 | 2000-01-13 | Novo Nordisk A/S | Seeding crystals for the preparation of peptides or proteins |
| HUE028288T2 (en) * | 2004-03-31 | 2016-12-28 | Toyama Chemical Co Ltd | Fine dispersion of sparingly soluble drug and process for producing the same |
| GR1009513B (en) * | 2017-10-05 | 2019-04-24 | Laboserve Φαρμακευτικη Βιομηχανια Α.Ε. | Drinkable pharmaceutical carbocysteine-containing solutions |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0813737B2 (en) * | 1986-12-19 | 1996-02-14 | 杏林製薬株式会社 | Syrup |
-
1991
- 1991-03-15 JP JP3051603A patent/JP2554784B2/en not_active Expired - Lifetime
Non-Patent Citations (1)
| Title |
|---|
| （財）日本公定書協会「日本薬局方解説書第十一改正」（昭６１−７−１８）廣川書店Ｐ．Ａ−６９−Ａ−７７ |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH04288013A (en) | 1992-10-13 |
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