JP4771044B2 - Mucosal fluid - Google Patents
Mucosal fluid Download PDFInfo
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- JP4771044B2 JP4771044B2 JP2004268172A JP2004268172A JP4771044B2 JP 4771044 B2 JP4771044 B2 JP 4771044B2 JP 2004268172 A JP2004268172 A JP 2004268172A JP 2004268172 A JP2004268172 A JP 2004268172A JP 4771044 B2 JP4771044 B2 JP 4771044B2
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- gellan gum
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- boric acid
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- 239000012530 fluid Substances 0.000 title description 5
- 238000002360 preparation method Methods 0.000 claims description 19
- 229920002148 Gellan gum Polymers 0.000 claims description 15
- 239000004372 Polyvinyl alcohol Substances 0.000 claims description 15
- 239000000216 gellan gum Substances 0.000 claims description 15
- 235000010492 gellan gum Nutrition 0.000 claims description 15
- 229920002451 polyvinyl alcohol Polymers 0.000 claims description 15
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 claims description 12
- 239000004327 boric acid Substances 0.000 claims description 12
- 239000000243 solution Substances 0.000 claims description 11
- 239000007788 liquid Substances 0.000 claims description 8
- 239000002738 chelating agent Substances 0.000 claims description 7
- 229910052784 alkaline earth metal Inorganic materials 0.000 claims description 6
- 150000001342 alkaline earth metals Chemical class 0.000 claims description 6
- ZGTMUACCHSMWAC-UHFFFAOYSA-L EDTA disodium salt (anhydrous) Chemical group [Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O ZGTMUACCHSMWAC-UHFFFAOYSA-L 0.000 claims description 5
- 239000007923 nasal drop Substances 0.000 claims description 5
- 239000001509 sodium citrate Substances 0.000 claims description 5
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 claims description 5
- 239000003109 Disodium ethylene diamine tetraacetate Substances 0.000 claims 1
- 235000019301 disodium ethylene diamine tetraacetate Nutrition 0.000 claims 1
- 230000000052 comparative effect Effects 0.000 description 9
- 239000003795 chemical substances by application Substances 0.000 description 8
- 210000004400 mucous membrane Anatomy 0.000 description 7
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- 239000003814 drug Substances 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 239000003889 eye drop Substances 0.000 description 6
- 238000009472 formulation Methods 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- 210000004877 mucosa Anatomy 0.000 description 6
- 229940012356 eye drops Drugs 0.000 description 5
- 238000000034 method Methods 0.000 description 5
- 229940100656 nasal solution Drugs 0.000 description 4
- 239000008213 purified water Substances 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 206010039101 Rhinorrhoea Diseases 0.000 description 3
- 235000011187 glycerol Nutrition 0.000 description 3
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 3
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 3
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 3
- 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 description 3
- 210000004379 membrane Anatomy 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 210000000214 mouth Anatomy 0.000 description 3
- 230000003232 mucoadhesive effect Effects 0.000 description 3
- 210000003928 nasal cavity Anatomy 0.000 description 3
- 208000010753 nasal discharge Diseases 0.000 description 3
- 229940100662 nasal drops Drugs 0.000 description 3
- 230000002459 sustained effect Effects 0.000 description 3
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 238000001879 gelation Methods 0.000 description 2
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 230000007794 irritation Effects 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- BDOYKFSQFYNPKF-UHFFFAOYSA-N 2-[2-[bis(carboxymethyl)amino]ethyl-(carboxymethyl)amino]acetic acid;sodium Chemical compound [Na].[Na].OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O BDOYKFSQFYNPKF-UHFFFAOYSA-N 0.000 description 1
- SGHZXLIDFTYFHQ-UHFFFAOYSA-L Brilliant Blue Chemical compound [Na+].[Na+].C=1C=C(C(=C2C=CC(C=C2)=[N+](CC)CC=2C=C(C=CC=2)S([O-])(=O)=O)C=2C(=CC=CC=2)S([O-])(=O)=O)C=CC=1N(CC)CC1=CC=CC(S([O-])(=O)=O)=C1 SGHZXLIDFTYFHQ-UHFFFAOYSA-L 0.000 description 1
- 241000218645 Cedrus Species 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical class OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 239000013522 chelant Substances 0.000 description 1
- 150000001860 citric acid derivatives Chemical class 0.000 description 1
- 238000013329 compounding Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 229940048820 edetates Drugs 0.000 description 1
- 108010025899 gelatin film Proteins 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 239000012669 liquid formulation Substances 0.000 description 1
- 229940126601 medicinal product Drugs 0.000 description 1
- 229910021645 metal ion Inorganic materials 0.000 description 1
- 210000003097 mucus Anatomy 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000005180 public health Effects 0.000 description 1
- 238000007127 saponification reaction Methods 0.000 description 1
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Description
本発明は粘膜適用液剤に関し、さらに詳しくは粘膜への付着性を向上した粘膜適用液剤に関する。 The present invention relates to a mucosa-applied solution, and more particularly to a mucosa-applied solution with improved adhesion to the mucosa.
鼻腔、口腔をはじめとする粘膜部位は、皮膚のようなバリアー能が無いため薬剤を投与すると素早く吸収される部位である。しかし、一般に粘膜は常に湿潤した状態にあるため、投与した薬物は粘液によって容易に希釈されることから薬効成分の利用率が低下してしまい、一般的に効果の持続の点では不十分である。 The mucous membrane region including the nasal cavity and the oral cavity is a region that is quickly absorbed when a drug is administered because it has no barrier function like the skin. However, since the mucous membrane is generally always moist, the administered drug is easily diluted with mucus, which reduces the utilization rate of medicinal ingredients and is generally insufficient in terms of sustained effect. .
このため、持続的な効果が得られる粘膜投与製剤が望まれていた。 For this reason, a mucosal preparation capable of obtaining a sustained effect has been desired.
ここで、ゲル状の製剤であれば粘膜に投与したときに薬物含有製剤が粘膜に付着し、薬効成分の利用率が上がるため持続した効果が期待できる。しかし、ゲル状の製剤は粘膜に均一に塗布がしにくく、特に鼻腔や口腔に対しては患部が広範囲であり塗布することが困難になることから、塗布する前の製剤は液状で均一に塗布しやすく、塗布した後に患部で速やかにゲル状皮膜を形成する製剤が好ましい。 Here, in the case of a gel-like preparation, a sustained effect can be expected because the drug-containing preparation adheres to the mucous membrane when administered to the mucosa and the utilization rate of the medicinal ingredients increases. However, gel-form preparations are difficult to apply evenly to the mucous membranes, especially the nasal cavity and oral cavity, because the affected area is wide and difficult to apply. A preparation that easily forms a gel film at the affected area after application is preferred.
従来、粘膜付着性を改善した点眼剤として、ポリビニルアルコール（ＰＶＡ）およびホウ酸を配合し眼中でゲル化する点眼剤（特許文献１）、涙液中のイオンによってゲル化するジェランガムを配合した点眼剤（特許文献２，３）などが知られている。
Conventionally, as eye drops with improved mucoadhesive properties, eye drops containing polyvinyl alcohol (PVA) and boric acid to gel in the eye (Patent Document 1), eye drops containing gellan gum gelled by ions in tear fluid Agents (
本発明者らは、付着性を改善した粘膜適用液剤の検討過程で、一般的な薬剤と粘膜付着性向上のためにジェランガムを配合して製剤設計を試みたところ、薬物とジェランガムとの相互作用によりジェランガムの配合量が制限され十分な粘膜付着性が得られないことがわかった。また、従来技術である、ＰＶＡおよびホウ酸を同時配合したものも、粘膜付着性が不十分なため十分な効果が得られないことがわかった。さらに、一般的に粘性を付与するために使用される高分子成分を配合すると、製剤自体に粘性を生じ、付着性は向上するものの噴霧性、滴下性に劣る製剤となってしまうこともわかった。 In the process of studying mucosa-applied solutions with improved adhesion, the present inventors tried to design a formulation by combining general drugs and gellan gum to improve mucoadhesion, and the interaction between the drug and gellan gum Thus, it was found that the blending amount of gellan gum was limited and sufficient mucoadhesiveness could not be obtained. Further, it was found that the conventional technique, in which PVA and boric acid were blended at the same time, could not obtain sufficient effects due to insufficient adhesion to the mucosa. Furthermore, it was also found that when a polymer component generally used for imparting viscosity is blended, the formulation itself becomes viscous and adhesion is improved, but the formulation is inferior in sprayability and dripping. .
このように、従来、点眼剤として知られている粘膜付着性を改善した技術は、粘膜に対する付着性の向上効果が十分なものではなく、さらなる効果の向上が求められていた。 Thus, the technology for improving mucoadhesiveness known as an eye drop has not been sufficient in improving the adhesion to mucous membranes, and further improvement of the effect has been demanded.
本発明は粘膜に対する付着性を向上させた液剤を得ることを目的とする。 An object of this invention is to obtain the liquid agent which improved the adhesiveness with respect to a mucous membrane.
そこで、本発明者らは種々検討した結果、ジェランガム、ＰＶＡおよびホウ酸を酸性領域で同時に配合し、アルカリ土類金属を含有しない製剤は、粘膜に塗布前は液剤であるが、粘膜に投与したときにゲル化して優れた付着性が発生することを見出し本発明を完成した。 Therefore, as a result of various studies, the inventors of the present invention blended gellan gum, PVA and boric acid at the same time in the acidic region, and preparations containing no alkaline earth metal were liquid before application to the mucosa, but were administered to the mucosa. The present invention was completed by finding that gelation sometimes causes excellent adhesion.
すなわち本発明は、
（１）ジェランガム、ポリビニルアルコールおよびホウ酸を配合し、アルカリ土類金属類を実質的に配合せず、ｐＨが１．５〜６．５である粘膜適用液剤。
（２）点鼻剤または口腔咽頭剤である（１）に記載の液剤。
（３）ポリビニルアルコールが０．０１w/v％〜１．４w/v％である（１）に記載の粘膜適用液剤。
（４）ホウ酸が０．０５w/v％〜２w/v％である（１）に記載の粘膜適用液剤。
（５）さらにキレート剤を配合する（１）〜（４）のいずれかに記載の粘膜適用液剤。
である。
That is, the present invention
(1) A mucosa-applied liquid formulation containing gellan gum, polyvinyl alcohol and boric acid, substantially free of alkaline earth metals, and having a pH of 1.5 to 6.5.
(2) The liquid preparation according to (1), which is a nasal drop or an oropharyngeal preparation.
(3) The mucosa-applied solution according to (1), wherein the polyvinyl alcohol is 0.01 w / v% to 1.4 w / v%.
(4) The mucosa-applied solution according to (1), wherein boric acid is 0.05 w / v% to 2 w / v%.
(5) The mucosa-applied solution according to any one of (1) to (4), further containing a chelating agent.
It is.
本発明では、ジェランガム、ＰＶＡおよびホウ酸を配合することにより、それぞれ単独で配合する場合と比較して相乗的に付着効果が向上する。 In the present invention, by adding gellan gum, PVA and boric acid, the adhesion effect is synergistically improved as compared with the case where each is added alone.
本発明では、ジェランガムの好ましい配合量は、製剤全体の０．０１〜２．０w/v%であり、さらに好ましい範囲は０．１〜１．０w/v%である。 In this invention, the preferable compounding quantity of gellan gum is 0.01-2.0 w / v% of the whole preparation, and a more preferable range is 0.1-1.0 w / v%.
本発明で用いるＰＶＡは、本発明の効果の点から、けん化度が78〜99mol%のものが好ましく、80〜95mol%のものがさらに好ましい。 The PVA used in the present invention preferably has a saponification degree of 78 to 99 mol%, more preferably 80 to 95 mol%, from the viewpoint of the effects of the present invention.
本発明で、ＰＶＡの好ましい配合量は製剤全体の０．０１〜１．４w/v%である。 In the present invention, the preferable amount of PVA is 0.01 to 1.4 w / v% of the whole preparation.
本発明で、ホウ酸の好ましい配合量は製剤全体の０．０５〜２．０w/v%である。 In the present invention, the preferable amount of boric acid is 0.05 to 2.0 w / v% of the whole preparation.
本発明ではアルカリ土類金属類を実質的に配合しないことを特徴とする。アルカリ土類金属類は、製剤中に混入すると製剤自体をゲル化させてしまうことから、鼻腔内や口腔内への噴霧性や眼内への滴下性を低下させ、薬剤の効果を低減させるおそれがあるからである。 The present invention is characterized by substantially not containing alkaline earth metals. Alkaline earth metals, when mixed in the formulation, cause the formulation to gel, thus reducing sprayability into the nasal cavity and oral cavity and dripping into the eye, reducing the effectiveness of the drug Because there is.
ここで、「実質的に配合しない」とは、アルカリ土類金属類が製剤中に極めて微量が混在してしまうような場合は配合するものとは考えないのは当然である。 Here, “substantially not blended” is naturally not considered to be blended when a very small amount of alkaline earth metal is mixed in the preparation.
本発明では液剤のｐＨは１．５〜６．５の範囲である必要がある。１．５未満であると、粘膜部位に塗布した際に刺激が生じるおそれがあり、６．５を超えると製剤自体に粘性が生じるため、噴霧性，滴下性が悪くなってしまうからである。 In the present invention, the pH of the solution needs to be in the range of 1.5 to 6.5. If it is less than 1.5, irritation may occur when it is applied to the mucosal site, and if it exceeds 6.5, the formulation itself becomes viscous, resulting in poor sprayability and dripping.
ここで、塗布する部位によって刺激感、使用感の点からは好ましいｐＨが使用目的により異なり、口腔咽頭剤はｐＨ１．５〜５．５、点鼻剤はｐＨ３〜６．５、点眼剤はｐＨ４．５〜６．５の範囲が好ましい。 Here, the preferred pH varies depending on the purpose of use depending on the application site, i.e., irritation and usability. A range of .5 to 6.5 is preferred.
本発明は粘膜に適用する製剤においてもっとも効果的に使用することができる。ここで、粘膜適用製剤とは点眼剤、点鼻剤、口腔咽頭剤などがあげられるが、点鼻剤、口腔咽頭剤とする場合に特に好ましい効果が得られる。 The present invention can be most effectively used in preparations applied to mucous membranes. Here, the preparation for mucosa includes eye drops, nasal drops, oropharyngeal agents, etc., and particularly preferable effects are obtained when they are used as nasal drops and oral pharyngeal agents.
本発明においては、さらにキレート剤を配合すると、製剤中でのジェランガムのゲル化を防ぐことができ，良好な噴霧性、滴下性を維持する上で好ましい。 In the present invention, if a chelating agent is further blended, gelation of gellan gum in the preparation can be prevented, which is preferable for maintaining good sprayability and dripping.
ここで、キレート剤とは金属イオンと結合してキレート化合物を形成する多座配位子のことであり、エデト酸塩類、クエン酸塩類などがあげられる。本発明で用いるのに好ましいキレート剤としてエチレンジアミン四酢酸二ナトリウム、クエン酸ナトリウムなどがあげられる。 Here, the chelating agent is a polydentate ligand that binds to a metal ion to form a chelate compound, and examples thereof include edetates and citrates. Preferred chelating agents for use in the present invention include ethylenediaminetetraacetic acid disodium, sodium citrate and the like.
本発明で、キレート剤を配合する場合の配合量は０．０００１〜１．０w/v%である。 In the present invention, when the chelating agent is blended, the blending amount is 0.0001 to 1.0 w / v%.
本発明の粘膜適用液剤は本発明の効果を損なわない範囲で、通常これらの製剤に配合される成分を配合して、通常の方法で製造することができる。 The mucosa-applied solution of the present invention can be produced by a usual method by blending components usually blended in these preparations, as long as the effects of the present invention are not impaired.
本発明は従来知られている技術と比較して、非常に高い粘膜付着性を有している。 The present invention has a very high mucoadhesive property as compared with a conventionally known technique.
以下、本発明を実施例および試験例によりさらに詳細に説明する。 Hereinafter, the present invention will be described in more detail with reference to examples and test examples.
ジェランガム 200mg
ポリビニルアルコール 1000mg
ホウ酸 1000mg
ＥＤＴＡ−２Ｎａ 50mg
グリセリン 900mg
クエン酸ナトリウム 適量
精製水 全100mL
ジェランガム及びＥＤＴＡ−２Ｎａを９０℃で加温溶解した後、別に溶解したＰＶＡ溶液と混合した。次いでその他の成分を溶解し、クエン酸ナトリウムでｐＨ５．０に調整して、精製水で全量を１００ｍＬにし点鼻用液剤を得た。得られた点鼻液の粘度は８．５ｍＰａ・sであった。
Gellan gum 200mg
Polyvinyl alcohol 1000mg
Boric acid 1000mg
EDTA-2Na 50mg
Glycerin 900mg
Sodium citrate
100 mL of purified water
Gellan gum and EDTA-2Na were dissolved by heating at 90 ° C., and then mixed with a separately dissolved PVA solution. Next, the other components were dissolved, adjusted to pH 5.0 with sodium citrate, and the total volume was adjusted to 100 mL with purified water to obtain a nasal solution. The viscosity of the obtained nasal solution was 8.5 mPa · s.
比較例１
ジェランガム 200mg
ＥＤＴＡ−２Ｎａ 50mg
グリセリン 2400mg
精製水 全100mL
実施例１からＰＶＡ、ホウ酸およびクエン酸ナトリウムを抜いて作製した。得られた点鼻液の粘度は７．４ｍＰａ・sであった。
Comparative Example 1
Gellan gum 200mg
EDTA-2Na 50mg
Glycerin 2400mg
100 mL of purified water
It was prepared by removing PVA, boric acid and sodium citrate from Example 1. The viscosity of the obtained nasal solution was 7.4 mPa · s.
比較例２
ポリビニルアルコール 1000mg
ヒドロキシプロピルメチルセルロース 300mg
ホウ酸 1000mg
ＥＤＴＡ−２Ｎａ 50mg
グリセリン 1100mg
精製水 全100mL
実施例１のジェランガムをヒドロキシプロピルメチルセルロース（ＨＰＭＣ）に変更して作製した。得られた点鼻液の粘度は６．７ｍＰａ・sであった。
Comparative Example 2
Polyvinyl alcohol 1000mg
Hydroxypropyl methylcellulose 300mg
Boric acid 1000mg
EDTA-2Na 50mg
Glycerin 1100mg
100 mL of purified water
It was prepared by changing the gellan gum of Example 1 to hydroxypropyl methylcellulose (HPMC). The viscosity of the obtained nasal solution was 6.7 mPa · s.
試験例１
実施例１および比較例１、２の製剤の付着性を以下の方法で確認した。ｐＨ９．１の人工鼻汁に浸漬したセルロース膜（１４ｃｍφ）を４５℃の角度で平板に設置し，膜に対して９０℃の角度で各点鼻液を２ｃｍの距離から１回噴霧した。１分後のセルロース膜上の液だれの長さを測定した（このとき、判定を容易にするため、各点鼻液に成分と相互作用のない色素（青色１号：ブリリアントブルーＦＣＦ：和光純薬製）を添加した）。その結果を図１および図２に示した。
Test example 1
The adhesion of the preparations of Example 1 and Comparative Examples 1 and 2 was confirmed by the following method. A cellulose membrane (14 cmφ) immersed in an artificial nasal discharge at pH 9.1 was placed on a flat plate at an angle of 45 ° C., and each nasal fluid was sprayed once from a distance of 2 cm at an angle of 90 ° C. with respect to the membrane. The length of the liquid dripping on the cellulose membrane after 1 minute was measured. (At this time, in order to facilitate the determination, each nasal fluid has no interaction with components in the nasal fluid (Blue No. 1: Brilliant Blue FCF: Wako Pure) Medicinal product) was added). The results are shown in FIG. 1 and FIG.
なお、人工鼻汁は佐分利らの報告(日本公衆衛生誌３９巻、６号、１９９２年「鼻汁によるスギ花粉の破裂」)を参考にして作製した。 Artificial nasal discharge was produced with reference to Toshi Sabe et al.'S report (Japan Public Health Magazine Vol. 39, No. 6, 1992 “Rupture of cedar pollen by nasal discharge”).
図から明らかなように、ジェランガム、ＰＶＡ、ホウ酸を配合した実施例１は比較例より有意に液だれがなく、顕著に付着性を向上させることがわかった。 As is clear from the figure, Example 1 containing gellan gum, PVA, and boric acid was found to be significantly free from dripping compared to the comparative example, and significantly improved adhesion.
実施例
以下の表に示した処方により実施例２および比較例３〜５の液剤を製造した。
Example The liquid agent of Example 2 and Comparative Examples 3-5 was manufactured by the prescription shown in the following table | surfaces.
次に、得られた液剤に試験例１と同様の試験を行い、液だれの試験を行った。結果を表１および図２に示した。なお、表中HPC：ヒドロキシプロピルセルロース、PVP：ポリビニルピロリドンを示す。 Next, a test similar to Test Example 1 was performed on the obtained liquid agent, and a dripping test was performed. The results are shown in Table 1 and FIG. In the table, HPC: hydroxypropylcellulose and PVP: polyvinylpyrrolidone are shown.
本発明により優れた粘膜付着性を持ち、かつ、噴霧性、滴下性も良好な液剤を提供することが可能になったので、点鼻剤、口腔咽頭剤、点眼剤などに使用可能である。 According to the present invention, it is possible to provide a liquid agent having excellent mucoadhesive property and having good sprayability and dripping property, so that it can be used for nasal drops, oropharyngeal agents, eye drops and the like.
Claims (3)
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| JP2004268172A JP4771044B2 (en) | 2004-09-15 | 2004-09-15 | Mucosal fluid |
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| JP2004268172A JP4771044B2 (en) | 2004-09-15 | 2004-09-15 | Mucosal fluid |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| ES2642042T3 (en) | 2006-04-21 | 2017-11-15 | Toko Yakuhin Kogyo Kabushiki Kaisha | Sprayable gel-like preparation for adhesion to the skin / mucosa, and administration system using the preparation |
| PL2011467T3 (en) | 2006-04-21 | 2021-04-06 | Toko Yakuhin Kogyo Kabushiki Kaisha | Fluid container and airless fluid dispensing system |
| JPWO2008053942A1 (en) * | 2006-10-31 | 2010-02-25 | 三栄源エフ・エフ・アイ株式会社 | Throat composition |
| JP7106852B2 (en) * | 2016-12-20 | 2022-07-27 | 大正製薬株式会社 | Suspension-type topical solution |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| JPS611358A (en) * | 1984-06-13 | 1986-01-07 | Kazuo Hara | Gelatinous food |
| FR2588189B1 (en) * | 1985-10-03 | 1988-12-02 | Merck Sharp & Dohme | LIQUID-GEL PHASE TRANSITION PHARMACEUTICAL COMPOSITION |
| JP2824460B2 (en) * | 1988-03-11 | 1998-11-11 | 株式会社ビーエムジー | Adhesive PVA hydrogel composition |
| JPH0427352A (en) * | 1990-05-22 | 1992-01-30 | Fuji Capsule Kk | Enteric soft capsule for health food |
| US5318780A (en) * | 1991-10-30 | 1994-06-07 | Mediventures Inc. | Medical uses of in situ formed gels |
| AU5599594A (en) * | 1992-11-16 | 1994-06-08 | Ciba-Geigy Ag | Polyvinyl alcohol/borate ophthalmic drug delivery system |
| JP3774975B2 (en) * | 1997-02-25 | 2006-05-17 | 大正製薬株式会社 | Gel-like sustained release composition |
| US6265444B1 (en) * | 1997-05-23 | 2001-07-24 | Insite Vision Incorporated | Ophthalmic composition |
| AU737442B2 (en) * | 1997-07-29 | 2001-08-16 | Alcon Laboratories, Inc. | Ophthalmic compositions containing galactomannan polymers and borate |
| JP4457422B2 (en) * | 1998-01-09 | 2010-04-28 | 大正製薬株式会社 | Nasal composition |
| JP2001081048A (en) * | 1999-09-10 | 2001-03-27 | Wakamoto Pharmaceut Co Ltd | Ocular hypotensive |
| JP2002040028A (en) * | 2000-07-28 | 2002-02-06 | Jsr Corp | Capillary immunoassay device and immunoassay method |
| JP2002154989A (en) * | 2000-11-14 | 2002-05-28 | Lion Corp | Ophthalmic composition and composition having improved retention of medicine in biological mucosa |
| JP2003128588A (en) * | 2001-08-10 | 2003-05-08 | Toray Ind Inc | Polysaccharide-containing composition and application thereof |
| JP4569080B2 (en) * | 2002-07-17 | 2010-10-27 | 大正製薬株式会社 | Nasal composition |
| EP1547604A1 (en) * | 2002-08-29 | 2005-06-29 | Toray Industries, Inc. | Medicinal composition for periodontal pocket administration containing bisphosphonic acid derivative or its salt as the active ingredient |
| WO2004019902A1 (en) * | 2002-08-30 | 2004-03-11 | Hisamitsu Pharmaceutical Co., Inc. | Adhesive gel composition for iontophoresis preparation and process for producing the same |
| JP2004175771A (en) * | 2002-11-29 | 2004-06-24 | Rohto Pharmaceut Co Ltd | Ketotifen-containing composition |
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