JPH08295622A - Aqueous suspended eye drop mixed with ionic polymer excellent in redispersibility - Google Patents
Aqueous suspended eye drop mixed with ionic polymer excellent in redispersibilityInfo
- Publication number
- JPH08295622A JPH08295622A JP8071049A JP7104996A JPH08295622A JP H08295622 A JPH08295622 A JP H08295622A JP 8071049 A JP8071049 A JP 8071049A JP 7104996 A JP7104996 A JP 7104996A JP H08295622 A JPH08295622 A JP H08295622A
- Authority
- JP
- Japan
- Prior art keywords
- eye drop
- formulation
- viscosity
- ionic polymer
- redispersibility
- 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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- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
【０００１】[0001]
【発明の属する技術分野】本発明はイオン性高分子およ
び金属陽イオンを配合し粘度が１００ｃＰ以下である難
溶性薬物を主薬とした水性懸濁型点眼剤に関するもので
あって、その水性懸濁型点眼剤は薬物の優れた再分散性
を示すことを特徴としている。TECHNICAL FIELD The present invention relates to an aqueous suspension type eye drop containing an ionic polymer and a metal cation as a main ingredient, which is a poorly soluble drug having a viscosity of 100 cP or less. The type ophthalmic solution is characterized by exhibiting excellent redispersibility of the drug.
【０００２】[0002]
【従来の技術】水に対する溶解度の低い薬物を点眼用と
して製剤化する場合、薬物を懸濁させた水性懸濁型点眼
剤とすることが考えられる。水性懸濁型点眼剤の市販製
品として、例えばフルオロメトロン点眼剤がある。2. Description of the Related Art When a drug having a low solubility in water is formulated as an eye drop, it is considered to be an aqueous suspension type eye drop in which the drug is suspended. Examples of commercially available aqueous suspension type eye drops include fluorometholone eye drops.
【０００３】一方、点眼剤中の薬物を眼瞼内に滞留させ
ることを主眼として、カルボキシビニルポリマー（以
下、ＣＶＰとする）を用いて特定の粘度を有する製剤、
いわゆるゲル状製剤とすることが報告されている（特開
昭５４−６７０２１号、特開昭５４−１１０３１２号、
特開平２−５０３２０１号公報）。On the other hand, a preparation having a specific viscosity using a carboxyvinyl polymer (hereinafter, referred to as CVP) with the main purpose of retaining a drug in an eye drop in the eyelid,
It has been reported that a so-called gel preparation is prepared (JP-A-54-67021, JP-A-54-110312,
JP-A-2-503201).
【０００４】ＣＶＰを水溶液にするとゲル状になり、高
い粘度を呈する。この高粘度の特性により、ゲルは角膜
上に長時間滞留することができ、そのゲルが少しずつ崩
壊することにより薬物が徐放化し、吸収量が増加すると
考えられている。したがって、上記記載の技術もその粘
度が少なくとも１０００ｃＰ以上のものが求められてお
り、この高い粘度が徐放化作用のために必要であると考
えられていた。When CVP is made into an aqueous solution, it becomes a gel and exhibits a high viscosity. It is believed that this high viscosity property allows the gel to stay on the cornea for a long time, and the gel gradually disintegrates to gradually release the drug and increase the absorption amount. Therefore, the technique described above is also required to have a viscosity of at least 1000 cP or more, and it was considered that this high viscosity is necessary for the sustained release action.
【０００５】また、超音波照射装置等で剪断処理したニ
ュートン型粘性を示すＣＶＰを用いると、吸収促進作用
を有する粘度が１００ｃＰ以下の点眼液を調製できるこ
とが知られている（特開平５−２４７３０８号公報）。Further, it is known that an eye drop having a viscosity of 100 cP or less having an absorption promoting effect can be prepared by using CVP having Newtonian viscosity which is sheared by an ultrasonic wave irradiation device or the like (Japanese Patent Laid-Open No. 247308/1993). Issue).
【０００６】しかしながら、いずれの公報にも、主薬を
懸濁させた水性製剤についての具体的な記載はない。さ
らに、懸濁させた主薬の再分散性についての記載もな
い。However, none of the publications specifically describes an aqueous preparation in which the active ingredient is suspended. Furthermore, there is no description about the redispersibility of the suspended main drug.
【０００７】[0007]
【発明が解決しようとする課題】水性懸濁型点眼剤は長
時間放置すると薬物が沈降するため、点眼時には容器を
振とうし再分散して用いなければならない。しかしなが
ら、沈降した薬物がケーキング等の２次凝集をおこすと
容易に再分散しなくなり、点眼時に長時間振とうしなけ
ればならない。再分散性をよくする方法の一つとして薬
物の粒子サイズを大きくすることが考えられるが、点眼
剤の場合、大きな粒子は眼に対する異物感が生じるとい
う欠点がある。The aqueous suspension type eye drops have a problem that the drug precipitates when left standing for a long time, and therefore the container must be shaken and redispersed before use. However, if the precipitated drug causes secondary aggregation such as caking, it will not be easily redispersed, and it must be shaken for a long time when instilled. One of the methods for improving the redispersibility is to increase the particle size of the drug, but in the case of eye drops, the large particles have a drawback that a foreign body sensation occurs in the eye.
【０００８】また、ＣＶＰを点眼剤に１００００ｃＰ以
上の粘度になるように配合すると眼軟膏状となるため、
点眼瓶より一定量点眼することはもちろん患者自身で点
眼することが困難となり、医師の手で結膜嚢内に塗布し
てもらう必要が生じる。さらに、点眼剤を調製する際、
溶液中に気泡が噛んで脱気しにくいことやろ過滅菌でき
ない等、困難な点がいくつかある。When CVP is added to eye drops so as to have a viscosity of 10000 cP or more, it becomes an eye ointment.
It becomes difficult to instill a fixed amount from the eye dropper and of course it is difficult for the patient to instill it himself / herself, and it becomes necessary to have the doctor apply it to the conjunctival sac. Furthermore, when preparing eye drops,
There are some difficulties such as air bubbles biting in the solution, making it difficult to deaerate and not being able to sterilize by filtration.
【０００９】このため、粘度が低く、再分散性に優れた
水性懸濁型点眼剤を検討する必要があった。Therefore, it was necessary to study an aqueous suspension type eye drop having a low viscosity and an excellent redispersibility.
【００１０】[0010]
【課題を解決するための手段】本発明者等は、粘度が低
くかつ再分散性の優れた難溶性薬物の水性懸濁型点眼剤
の探索を行った結果、ＣＶＰやカルボキシメチルセルロ
ースナトリウム（以下、ＣＭＣ．Ｎａとする）等のイオ
ン性高分子とナトリウムイオンやカリウムイオン等の金
属陽イオンを配合し粘度を１００ｃＰ以下とすることに
より、難溶性薬物の再分散性に優れている水性懸濁型点
眼剤（以下、本発明点眼剤とする）が得られることを見
いだした。Means for Solving the Problems As a result of a search for an aqueous suspension type eye drop of a poorly soluble drug having a low viscosity and excellent redispersibility, the present inventors have found that CVP and sodium carboxymethylcellulose (hereinafter, CMC.Na) and other ionic polymers and metal cations such as sodium ions and potassium ions to give a viscosity of 100 cP or less, which is excellent in redispersibility of poorly soluble drugs. It was found that an eye drop (hereinafter, referred to as an eye drop of the present invention) can be obtained.
【００１１】[0011]
【発明の実施の形態】本発明点眼剤に用いられるイオン
性高分子とは、ＣＶＰ、ＣＭＣ．Ｎａ、コンドロイチン
硫酸、ヘパリン硫酸等の陰イオン性高分子が好ましく、
特に合成高分子であるＣＶＰやＣＭＣ．Ｎａがより好ま
しい。BEST MODE FOR CARRYING OUT THE INVENTION The ionic polymer used in the eye drop of the present invention includes CVP, CMC. Anionic polymers such as Na, chondroitin sulfate and heparin sulfate are preferable,
Especially synthetic polymers such as CVP and CMC. Na is more preferred.
【００１２】イオン性高分子の使用濃度は適宜選択でき
るが、ＣＶＰであれば、０．００１〜０．２％（ｗ／
ｖ）、特に０．００５〜０．１％（ｗ／ｖ）が好まし
く、ＣＭＣ．Ｎａであれば、０．０１〜０．１％（ｗ／
ｖ）が好ましい。The concentration of the ionic polymer to be used can be appropriately selected, but in the case of CVP, 0.001 to 0.2% (w /
v), especially 0.005-0.1% (w / v) is preferred, and CMC. If Na, 0.01-0.1% (w /
v) is preferred.
【００１３】また、本発明点眼剤に用いられる金属陽イ
オンとは、１価または２価の金属陽イオンを示すが、ナ
トリウムイオン、カリウムイオン等の１価の金属イオン
が好ましい。金属陽イオンの濃度が高くなりすぎると薬
物の再分散性が悪くなり、濃度が低すぎると点眼剤の粘
度が高くなり、所望の点眼剤は得られなくなる。その使
用濃度範囲は、２０〜２００ｍＭ、特に１００〜１５０
ｍＭが好ましい。金属陽イオンは、例えば塩化ナトリウ
ム、塩化カリウム、塩化カルシウム、硫酸ナトリウム、
硫酸カリウム、硫酸カルシウム、リン酸二水素ナトリウ
ム、リン酸水素二ナトリウム、炭酸ナトリウム、炭酸カ
リウム、炭酸カルシウム、酢酸ナトリウム、エデト酸ナ
トリウム、クエン酸ナトリウム等を用いることによって
供給できる。The metal cation used in the eye drop of the present invention is a monovalent or divalent metal cation, and monovalent metal ions such as sodium ion and potassium ion are preferred. If the concentration of the metal cation is too high, the redispersibility of the drug will be poor, and if the concentration is too low, the viscosity of the eye drop will be high and the desired eye drop cannot be obtained. The concentration range used is 20 to 200 mM, especially 100 to 150
mM is preferred. Metal cations include, for example, sodium chloride, potassium chloride, calcium chloride, sodium sulfate,
It can be supplied by using potassium sulfate, calcium sulfate, sodium dihydrogen phosphate, disodium hydrogen phosphate, sodium carbonate, potassium carbonate, calcium carbonate, sodium acetate, sodium edetate, sodium citrate and the like.
【００１４】また、ｐＨは点眼剤の粘度に影響を与え
る。すなわち、ｐＨが高くなるにつれ粘度も高くなり、
ｐＨが低くなるにつれ粘度も低くなる。さらに、ｐＨは
眼刺激性にも影響を与え、高すぎても低すぎても好まし
くない。本発明点眼剤に好適に用いられるｐＨの範囲は
４．０〜８．０、より好ましくは４．５〜７．５であ
る。The pH also affects the viscosity of the eye drop. That is, the higher the pH, the higher the viscosity,
The lower the pH, the lower the viscosity. Further, the pH also affects the eye irritation, and it is not preferable that the pH is too high or too low. The pH range suitably used for the eye drop of the present invention is 4.0 to 8.0, and more preferably 4.5 to 7.5.
【００１５】本発明点眼剤に用いられる難溶性薬物と
は、酪酸クロベタゾン、フルオロメトロン、酢酸ハイド
ロコーチゾン、デキサメサゾン、インドメタシン等水に
対する溶解度の低いものを示す。特にフルオロメトロン
点眼剤に本発明の技術が好適に応用できる。The sparingly soluble drug used in the eye drop of the present invention is clobetasone butyrate, fluorometholone, hydrocortisone acetate, dexamethasone, indomethacin and the like having low solubility in water. In particular, the technique of the present invention can be preferably applied to fluorometholone eye drops.
【００１６】難溶性薬物の使用濃度は適宜選択できる
が、フルオロメトロンであれば、０．００２〜０．１％
（ｗ／ｖ）、特に０．０２〜０．１％（ｗ／ｖ）が好ま
しい。The concentration of the poorly soluble drug to be used can be appropriately selected, but in the case of fluorometholone, it is 0.002-0.1%.
(W / v), especially 0.02 to 0.1% (w / v) is preferable.
【００１７】本発明点眼剤の粘度はイオン性高分子や金
属陽イオンの使用濃度で１００ｃＰ以下であるが、２０
ｃＰ以下の粘度のものがより好ましい。Although the viscosity of the eye drop of the present invention is 100 cP or less at the concentration used of the ionic polymer and the metal cation, 20
It is more preferable that the viscosity is cP or less.
【００１８】本発明点眼剤の有用性を調べるべく、本発
明点眼剤の再分散性について検討した。その結果、詳細
なデータについては後述の再分散性試験の項で述べる
が、本発明点眼剤は粘度が１００ｃＰ以下で、かつ優れ
た再分散性を有し、難溶性薬物、特にフルメオロトロン
を有効成分とする水性懸濁型点眼剤として有用であるこ
とが認められた。本発明の効果は、高分子による立体的
保護効果ならびに静電気的な保護効果によって達成され
ると考えられる。In order to examine the usefulness of the eye drop of the present invention, the redispersibility of the eye drop of the present invention was examined. As a result, detailed data will be described later in the section of redispersibility test. However, the eye drop of the present invention has a viscosity of 100 cP or less and has excellent redispersibility, and a poorly soluble drug, particularly flumeorotron, is an active ingredient. Was found to be useful as an aqueous suspension type eye drop. The effect of the present invention is considered to be achieved by the steric protection effect and the electrostatic protection effect of the polymer.
【００１９】本発明点眼剤の一般的な調製法としては次
のものがあげられる。滅菌精製水にイオン性高分子を加
え、攪拌しながら等張化剤、緩衝化剤などを加える。そ
こへ、薬物および界面活性剤の滅菌精製水懸濁液を加
え、さらに激しく攪拌した後、分散させて本発明点眼剤
を得る。The following are typical methods for preparing the eye drop of the present invention. An ionic polymer is added to sterile purified water, and an isotonic agent, a buffering agent, etc. are added while stirring. A sterile purified water suspension of the drug and the surfactant is added thereto, and the mixture is further vigorously stirred and then dispersed to obtain the eye drop of the present invention.
【００２０】上記の等張化剤とは塩化ナトリウム、濃グ
リセリン等を、緩衝化剤とはリン酸ナトリウム、酢酸ナ
トリウム等を、界面活性剤とはポリオキシエチレンソル
ビタンモノオレート（以下、ポリソベート８０とする）
等を示し、エデト酸ナトリウム、クエン酸ナトリウム等
の安定化剤、塩化ベンザルコニウム、パラベン等の防腐
剤などを必要に応じて必要量加えることができる。The above-mentioned isotonic agent is sodium chloride, concentrated glycerin, etc., the buffering agent is sodium phosphate, sodium acetate, etc., and the surfactant is polyoxyethylene sorbitan monooleate (hereinafter referred to as polysorbate 80). Do)
And the like, and stabilizers such as sodium edetate and sodium citrate, and preservatives such as benzalkonium chloride and paraben can be added in necessary amounts as necessary.
【００２１】以下に、本発明点眼剤の製剤処方例および
再分散性試験の結果を示すが、これらの例は本発明をよ
りよく理解するためのものであり、本発明の範囲を限定
するものではない。The following are examples of the formulation of the eye drops of the present invention and the results of the redispersibility test. These examples are for better understanding of the present invention and limit the scope of the present invention. is not.
【００２２】[0022]
［製剤例］ 実施例１（製剤１） 滅菌精製水（４０ｍｌ）にＣＶＰ（５ｍｇ）を加え、攪
拌しながら塩化ナトリウム（８００ｍｇ）、リン酸二水
素ナトリウム２水和物（２０ｍｇ）、リン酸水素二ナト
リウム１２水和物（２００ｍｇ）を加える。そこへフル
オロメトロン（１００ｍｇ）およびポリソルベート８０
（３０ｍｇ）の滅菌精製水（４０ｍｌ）件懸濁液を加
え、さらに激しく攪拌した後、滅菌精製水を加えて全量
を１００ｍｌとして、ｐＨ５．０、粘度０．９３ｃＰ、
金属陽イオン濃度１４０ｍＭの０．１％（ｗ／ｖ）フル
オロメトロン点眼剤を調製する。[Formulation Example] Example 1 (Formulation 1) CVP (5 mg) was added to sterile purified water (40 ml), and sodium chloride (800 mg), sodium dihydrogen phosphate dihydrate (20 mg) and hydrogen phosphate were added with stirring. Add disodium dodecahydrate (200 mg). There fluorometholone (100 mg) and polysorbate 80
After adding (30 mg) suspension of sterile purified water (40 ml) and further stirring vigorously, sterile purified water was added to bring the total amount to 100 ml, pH 5.0, viscosity 0.93 cP,
A 0.1% (w / v) fluorometholone eye drop having a metal cation concentration of 140 mM is prepared.
【００２３】実施例２ フルオロメトロン、ポリソルベート８０、塩化ナトリウ
ム、リン酸二水素ナトリウム２水和物およびリン酸水素
二ナトリウム１２水和物の濃度を実施例１と同様に、イ
オン性高分子を表１のように設定し、０．１％（ｗ／
ｖ）フルオロメトロン点眼剤を調製する。なお、イオン
性高分子を配合しない製剤（参考製剤１）および非イオ
ン性高分子であるポリビニルアルコール（以下、ＰＶＡ
とする）を配合した製剤（参考製剤２）についても記
す。各製剤のｐＨは５．０、金属陽イオン濃度は１４０
ｍＭである。表中の各成分の数字は重量％（ｗ／ｖ）を
示す。Example 2 The concentrations of fluorometholone, polysorbate 80, sodium chloride, sodium dihydrogen phosphate dihydrate and disodium hydrogen phosphate dodecahydrate were measured in the same manner as in Example 1 to represent the ionic polymer. Set as 1 and 0.1% (w /
v) Prepare fluorometholone eye drops. In addition, a preparation containing no ionic polymer (Reference Preparation 1) and polyvinyl alcohol (hereinafter, PVA) which is a nonionic polymer
The formulation (Reference formulation 2) containing the same) is also described. The pH of each preparation is 5.0 and the metal cation concentration is 140.
It is mM. The number of each component in the table indicates weight% (w / v).
【００２４】[0024]
【表１】 ＣＶＰ ＣＭＣ．Ｎａ ＰＶＡ 粘度（ｃＰ） 製剤 ２ 製剤 ３ 製剤 ４ 製剤 ５ 製剤 ６ 参考製剤１ 参考製剤２ ０．０１ ０．１ −−−− −−−− −−−− −−−− −−−− −−−− −−−− ０．０１ ０．０５ ０．１ −−−− −−−− −−−− −−−− −−−− −−−− −−−− −−−− ０．０１ １．２９ １．３８ ０．９５ １．０４ ２．６６ ０．８９ ０．９０Table 1 CVP CMC. Na PVA Viscosity (cP) Formulation 2 Formulation 3 Formulation 4 Formulation 5 Formulation 6 Reference Formulation 1 Reference Formulation 2 0.01 0.1 −−−−−−−−−−−−−−−−−−−−−−− −−−−−− 0.01 0.05 0.1 −−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−− 0.01 1.29 1.38 0.95 1.04 2.66 0.89 0.90
【００２５】実施例３（製剤７） 滅菌精製水（４０ｍｌ）にＣＶＰ（５ｍｇ）を加え、攪
拌しながら塩化ナトリウム（８００ｍｇ）、リン酸二水
素ナトリウム２水和物（２０ｍｇ）、リン酸水素二ナト
リウム１２水和物（２００ｍｇ）、エデト酸ナトリウム
（１０ｍｇ）、塩化ベンザルコニウム（５ｍｇ）を加え
る。そこへフルオロメトロン（２０ｍｇ）およびポリソ
ルベート８０（３０ｍｇ）の滅菌精製水（４０ｍｌ）件
懸濁液を加え、さらに激しく攪拌した後、滅菌精製水を
加えて全量を１００ｍｌとして、ｐＨ７．３、粘度１０
０ｃＰ以下、金属陽イオン濃度１４０ｍＭの０．０２％
（ｗ／ｖ）フルオロメトロン点眼剤を調製する。Example 3 (Formulation 7) CVP (5 mg) was added to sterile purified water (40 ml), and sodium chloride (800 mg), sodium dihydrogen phosphate dihydrate (20 mg) and dihydrogen phosphate were added with stirring. Add sodium dodecahydrate (200 mg), sodium edetate (10 mg), benzalkonium chloride (5 mg). A suspension of fluorometholone (20 mg) and polysorbate 80 (30 mg) in sterile purified water (40 ml) was added thereto, and the mixture was vigorously stirred, and then sterile purified water was added to bring the total volume to 100 ml, pH 7.3, and viscosity 10
0 cP or less, metal cation concentration of 140 mM, 0.02%
(W / v) Fluorometholone eye drops are prepared.
【００２６】実施例４ フルオロメトロン、ポリソルベート８０、塩化ナトリウ
ム、リン酸二水素ナトリウム２水和物、リン酸水素二ナ
トリウム１２水和物、エデト酸ナトリウムおよび塩化ベ
ンザルコニウムの濃度を実施例３と同様に、フルオロメ
トロンおよびイオン性高分子を表２のように設定し、フ
ルオロメトロン点眼剤を調製する。なお、各製剤のｐＨ
は７．３、粘度は１００ｃＰ以下、金属陽イオン濃度は
１４０ｍＭである。表中の各成分の数字は重量％（ｗ／
ｖ）を示す。Example 4 The concentrations of fluorometholone, polysorbate 80, sodium chloride, sodium dihydrogen phosphate dihydrate, disodium hydrogen phosphate dodecahydrate, sodium edetate and benzalkonium chloride were compared with those in Example 3. Similarly, a fluorometholone and an ionic polymer are set as shown in Table 2, and a fluorometholone eye drop is prepared. The pH of each formulation
Is 7.3, the viscosity is 100 cP or less, and the metal cation concentration is 140 mM. The numbers of each component in the table are% by weight (w /
v) is shown.
【００２７】[0027]
【表２】 フルオロメトロン ＣＶＰ ＣＭＣ．Ｎａ 粘度（ｃＰ） 製剤 ８ 製剤 ９ 製剤１０ 製剤１１ 製剤１２ 製剤１３ 製剤１４ 製剤１５ 製剤１６ 製剤１７ ０．０２ ０．０１ ０．０１ ０．０１ ０．０１ ０．０１ ０．０１ ０．０１ ０．０１ ０．０１ ０．０５ ０．００１ ０．００５ ０．０１ ０．０５ ０．１ ０．２ −−−−− −−−−− −−−−− −−−− −−−− −−−− −−−− −−−− −−−− −−−− ０．０１ ０．０５ ０．１ １６．１ １１．８ １２．５ １２．４ １７．７ ２５．９ ６７．８ １２．８ １５．５ １９．５Table 2 Fluorometholone CVP CMC. Na viscosity (cP) formulation 8 formulation 9 formulation 10 formulation 11 formulation 12 formulation 13 formulation 14 formulation 15 formulation 16 formulation 17 0.02 0.01 0.01 0.01 0.01 0.01 0.01 0.01 0.01 0 .01 0.01 0.05 0.001 0.005 0.01 0.05 0.1 0.2 ------------------------------ −−−−−−−−−−− −−−−−−−− 0.01 0.05 0.1 16.1 11.8 12.5 12.4 17.7 25.9 67.8 12 .8 15.5 19.5
【００２８】［再分散性試験］均一に分散するまでの回
転数によって、懸濁液における再分散性を評価するMatt
hews らの方法が知られている（J. Pharm. Sci, 57, 56
9-573 (1968)）。そこで、この文献に記載された方法に
準じて、本発明点眼剤の再分散性を検討した。[Redispersibility Test] Matte for evaluating redispersibility in suspension by the number of revolutions until uniform dispersion
The method of hews et al. is known (J. Pharm. Sci, 57, 56.
9-573 (1968)). Therefore, the redispersibility of the eye drop of the present invention was examined according to the method described in this document.
【００２９】（実験方法）懸濁液５０ｍｌを試験管に入
れ室温で２週間静置した後、均一に分散するまで一定速
度（２ｃｙｃｌｅｓ／ｓｅｃ）で１８０゜反転させ再分
散性を観察した。(Experimental method) 50 ml of the suspension was placed in a test tube and allowed to stand at room temperature for 2 weeks, then it was inverted 180 ° at a constant speed (2 cycles / sec) until it was uniformly dispersed, and the redispersibility was observed.
【００３０】（結果）表３に実験結果の一例として、フ
ルオロメトロンを主成分とした製剤のうちで、ＣＶＰを
含んだ処方の製剤（製剤１、製剤２、製剤３）およびＣ
ＭＣ．Ｎａを含んだ処方の製剤（製剤４、製剤５、製剤
６）における、均一に再分散するのに要した反転回数を
示す。また、フルオロメトロンを主成分とした、高分子
を含まない処方の製剤（参考製剤１）および非イオン性
の高分子であるＰＶＡを含んだ処方の製剤（参考製剤
２）についても同様に示した。(Results) As an example of the experimental results in Table 3, among the preparations mainly containing fluorometholone, the preparations containing CVP (Preparation 1, Preparation 2, Preparation 3) and C
MC. The number of times of reversal required for uniform redispersion in the formulations containing Na (formulation 4, formulation 5, formulation 6) is shown. In addition, a formulation containing a polymer containing fluorometholone as a main component (reference formulation 1) and a formulation containing a nonionic polymer PVA (reference formulation 2) are also shown in the same manner. .
【００３１】[0031]
【表３】 反転回数 製剤 １ 製剤 ２ 製剤 ３ 製剤 ４ 製剤 ５ 製剤 ６ 参考製剤１ 参考製剤２ １１ ５ ３ ２９ ２０ １０ １０１ ５０[Table 3] Number of inversions Preparation 1 Preparation 2 Preparation 3 Preparation 4 Preparation 5 Preparation 6 Reference Preparation 1 Reference Preparation 2 11 5 3 29 29 20 10 101 50
【００３２】表３に示したように、イオン性高分子と金
属陽イオンを配合することで、優れた再分散性が認めら
れ、その程度はイオン性高分子の配合濃度に依存してい
た。また、これら各製剤の粘度は、いずれも２０ｃＰ以
下と非常に低いものであった。As shown in Table 3, by blending the ionic polymer and the metal cation, excellent redispersibility was recognized, and the degree thereof depended on the blending concentration of the ionic polymer. In addition, the viscosity of each of these preparations was very low at 20 cP or less.
【００３３】[0033]
【発明の効果】上記の再分散性試験の結果から、本発明
点眼剤は優れた再分散性を有しており、難溶性薬物、特
にフルオロメトロンを有効成分とする点眼剤として有用
であることが見いだされた。 整理番号 ９６Ｊ０６Ｅ 表を記載した書面 明細書From the results of the above redispersibility test, the eye drop of the present invention has excellent redispersibility and is useful as an eye drop containing a poorly soluble drug, particularly fluorometholone as an active ingredient. Was found. Reference number 96J06E Written statement with table
【表１】 ＣＶＰ ＣＭＣ．Ｎａ ＰＶＡ 粘度（ｃＰ） 製剤 ２ 製剤 ３ 製剤 ４ 製剤 ５ 製剤 ６ 参考製剤１ 参考製剤２ ０．０１ ０．１ −−−− −−−− −−−− −−−− −−−− −−−− −−−− ０．０１ ０．０５ ０．１ −−−− −−−− −−−− −−−− −−−− −−−− −−−− −−−− ０．０１ １．２９ １．３８ ０．９５ １．０４ ２．６６ ０．８９ ０．９０Table 1 CVP CMC. Na PVA Viscosity (cP) Formulation 2 Formulation 3 Formulation 4 Formulation 5 Formulation 6 Reference Formulation 1 Reference Formulation 2 0.01 0.1 −−−−−−−−−−−−−−−−−−−−−−− −−−−−− 0.01 0.05 0.1 −−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−− 0.01 1.29 1.38 0.95 1.04 2.66 0.89 0.90
【表２】 フルオロメトロン ＣＶＰ ＣＭＣ．Ｎａ 粘度（ｃＰ） 製剤 ８ 製剤 ９ 製剤１０ 製剤１１ 製剤１２ 製剤１３ 製剤１４ 製剤１５ 製剤１６ 製剤１７ ０．０２ ０．０１ ０．０１ ０．０１ ０．０１ ０．０１ ０．０１ ０．０１ ０．０１ ０．０１ ０．０５ ０．００１ ０．００５ ０．０１ ０．０５ ０．１ ０．２ −−−−− −−−−− −−−−− −−−− −−−− −−−− −−−− −−−− −−−− −−−− ０．０１ ０．０５ ０．１ １．２９ １．３８ ０．９５ １．０４ ２．６６ ０．８９ ０．９０Table 2 Fluorometholone CVP CMC. Na viscosity (cP) formulation 8 formulation 9 formulation 10 formulation 11 formulation 12 formulation 13 formulation 14 formulation 15 formulation 16 formulation 17 0.02 0.01 0.01 0.01 0.01 0.01 0.01 0.01 0.01 0 .01 0.01 0.05 0.001 0.005 0.01 0.05 0.1 0.2 ------------------------------ −−−−−−−−−−−−−−−−−−− 0.01 0.05 0.1 1.29 1.38 0.95 1.04 2.66 0.89 0.90
【表３】 反転回数 製剤 １ 製剤 ２ 製剤 ３ 製剤 ４ 製剤 ５ 製剤 ６ 参考製剤１ 参考製剤２ １１ ５ ３ ２９ ２０ １０ １０１ ５０ − １ − 整理番号 ９６Ｊ０６Ｅ − ２ − 整理番号 ９６Ｊ０６Ｅ[Table 3] Number of reversals Formulation 1 Formulation 2 Formulation 3 Formulation 4 Formulation 5 Formulation 6 Reference Formulation 1 Reference Formulation 2 11 5 3 29 20 20 10 101 50-1-Serial Number 96J06E-2-- Serial Number 96J06E
Claims (10)
合し粘度を１００ｃＰ以下とすることにより、難溶性薬
物の再分散性を高めたことを特徴とする難溶性薬物の水
性懸濁型点眼剤。1. An aqueous suspension type eye drop of a sparingly soluble drug, characterized in that the redispersibility of the sparingly soluble drug is enhanced by adding an ionic polymer and a metal cation so that the viscosity is 100 cP or less. .
である請求項１記載の水性懸濁型点眼剤。2. The concentration of metal cation is 20 to 200 mM.
The aqueous suspension type eye drop according to claim 1.
マーまたはカルボキシメチルセルロースナトリウムであ
る請求項１記載の水性懸濁型点眼剤。3. The aqueous suspension type eye drop according to claim 1, wherein the ionic polymer is a carboxyvinyl polymer or sodium carboxymethyl cellulose.
マーである請求項１記載の水性懸濁型点眼剤。4. The aqueous suspension type eye drop according to claim 1, wherein the ionic polymer is a carboxyvinyl polymer.
００１〜０．２％（ｗ／ｖ）である請求項４記載の水性
懸濁型点眼剤。5. A carboxyvinyl polymer concentration of 0.
It is 001-0.2% (w / v), The aqueous suspension type eye drop of Claim 4.
載の水性懸濁型点眼剤。6. The aqueous suspension-type eye drop according to claim 1, which has a pH of 4.0 to 8.0.
求項１記載の水性懸濁型点眼剤。7. The aqueous suspension type eye drop according to claim 1, wherein the poorly soluble drug is fluorometholone.
ポリマーを０．００１〜０．２％（ｗ／ｖ）および金属
陽イオンを２０〜２００ｍＭ配合し、ｐＨが４．０〜
８．０かつ粘度を１００ｃＰ以下とすることにより、難
溶性薬物の再分散性を高めたことを特徴とする難溶性薬
物の水性懸濁型点眼剤。8. A carboxyvinyl polymer, which is an ionic polymer, is added in an amount of 0.001 to 0.2% (w / v) and a metal cation of 20 to 200 mM, and the pH is 4.0 to 4.0.
An aqueous suspension-type eye drop of a poorly soluble drug, which has a redispersibility of the poorly soluble drug enhanced by setting the viscosity to 8.0 and the viscosity to 100 cP or less.
ポリマーを０．００５〜０．１％（ｗ／ｖ）および金属
陽イオンを１００〜１５０ｍＭ配合し、ｐＨが４．５〜
７．５かつ粘度を２０ｃＰ以下とすることにより、難溶
性薬物の再分散性を高めたことを特徴とする難溶性薬物
の水性懸濁型点眼剤。9. A carboxyvinyl polymer, which is an ionic polymer, is added in an amount of 0.005 to 0.1% (w / v) and a metal cation of 100 to 150 mM, and a pH of 4.5 to 4.5.
An aqueous suspension-type eye drop of a poorly soluble drug, characterized in that the redispersibility of the poorly soluble drug is enhanced by setting the viscosity to 7.5 and the viscosity to 20 cP or less.
ルポリマーを０．００５〜０．１％（ｗ／ｖ）および金
属陽イオンを１００〜１５０ｍＭ配合し、ｐＨが４．５
〜７．５かつ粘度を２０ｃＰ以下とすることにより、再
分散性を高めたことを特徴とするフルオロメトロンの水
性懸濁型点眼剤。10. A carboxyvinyl polymer, which is an ionic polymer, is added in an amount of 0.005 to 0.1% (w / v) and a metal cation is added in an amount of 100 to 150 mM, and the pH is 4.5.
An aqueous suspension type ophthalmic solution of fluorometholone characterized in that the redispersibility is enhanced by setting the viscosity to ˜7.5 and the viscosity to 20 cP or less.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP07104996A JP3269770B2 (en) | 1995-03-02 | 1996-03-01 | Aqueous suspension eye drops containing ionic polymer with excellent redispersibility |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP6871995 | 1995-03-02 | ||
| JP7-68719 | 1995-03-02 | ||
| JP07104996A JP3269770B2 (en) | 1995-03-02 | 1996-03-01 | Aqueous suspension eye drops containing ionic polymer with excellent redispersibility |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH08295622A true JPH08295622A (en) | 1996-11-12 |
| JP3269770B2 JP3269770B2 (en) | 2002-04-02 |
Family
ID=26409920
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP07104996A Expired - Fee Related JP3269770B2 (en) | 1995-03-02 | 1996-03-01 | Aqueous suspension eye drops containing ionic polymer with excellent redispersibility |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP3269770B2 (en) |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1999037286A1 (en) * | 1998-01-22 | 1999-07-29 | Santen Pharmaceutical Co., Ltd. | Fluorometholone suspension eye drops |
| JP2002501884A (en) * | 1998-01-30 | 2002-01-22 | ノバルテイス・コンシユーマー・ヘルス・エス・アー | Nasal solution |
| US6683070B2 (en) | 1997-05-14 | 2004-01-27 | Senju Pharmaceutical Co., Ltd. | Aqueous suspension with good redispersibility |
| WO2010111115A1 (en) * | 2009-03-24 | 2010-09-30 | Bausch & Lomb Incorporated | Method for preparing suspensions of low-solubility materials |
| US8481516B2 (en) | 2006-12-27 | 2013-07-09 | Takeda Gmbh | Ciclesonide containing sterile aqueous suspension |
| WO2016006702A1 (en) * | 2014-07-11 | 2016-01-14 | 富士フイルム株式会社 | Aqueous ophthalmic composition |
| US9775802B2 (en) | 2009-03-24 | 2017-10-03 | Bausch & Lomb Incorporated | Method for preparing suspensions of low-solubility materials |
| US10799589B2 (en) | 2013-03-13 | 2020-10-13 | Buzzard Pharmaceuticals AB | Chimeric cytokine formulations for ocular delivery |
-
1996
- 1996-03-01 JP JP07104996A patent/JP3269770B2/en not_active Expired - Fee Related
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6683070B2 (en) | 1997-05-14 | 2004-01-27 | Senju Pharmaceutical Co., Ltd. | Aqueous suspension with good redispersibility |
| WO1999037286A1 (en) * | 1998-01-22 | 1999-07-29 | Santen Pharmaceutical Co., Ltd. | Fluorometholone suspension eye drops |
| US6288049B1 (en) | 1998-01-22 | 2001-09-11 | Santen Pharmaceutical Co., Ltd. | Fluorometholone ophthalmic suspension |
| JP2002501884A (en) * | 1998-01-30 | 2002-01-22 | ノバルテイス・コンシユーマー・ヘルス・エス・アー | Nasal solution |
| US8481516B2 (en) | 2006-12-27 | 2013-07-09 | Takeda Gmbh | Ciclesonide containing sterile aqueous suspension |
| WO2010111115A1 (en) * | 2009-03-24 | 2010-09-30 | Bausch & Lomb Incorporated | Method for preparing suspensions of low-solubility materials |
| US9775802B2 (en) | 2009-03-24 | 2017-10-03 | Bausch & Lomb Incorporated | Method for preparing suspensions of low-solubility materials |
| US10799589B2 (en) | 2013-03-13 | 2020-10-13 | Buzzard Pharmaceuticals AB | Chimeric cytokine formulations for ocular delivery |
| WO2016006702A1 (en) * | 2014-07-11 | 2016-01-14 | 富士フイルム株式会社 | Aqueous ophthalmic composition |
| JPWO2016006702A1 (en) * | 2014-07-11 | 2017-04-27 | 富士フイルム株式会社 | Ophthalmic aqueous composition |
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| Publication number | Publication date |
|---|---|
| JP3269770B2 (en) | 2002-04-02 |
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