JP3402195B2 - Aqueous suspension with good redispersibility - Google Patents

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to an aqueous suspension having good redispersibility.

[0002]

2. Description of the Related Art When a poorly water-soluble drug is formulated into eye drops, nasal drops, injections, etc., it may be considered to be an aqueous suspension in which the drug is suspended. When such an aqueous suspension is left for a long period of time, a drug as dispersed particles (hereinafter, sometimes simply referred to as dispersed particles) aggregates and the dispersed particles become large, or the dispersed particles sediment and the precipitated dispersed particles become Since secondary aggregation such as caking occurs, it is possible to prevent aggregation or sedimentation of dispersed particles as much as possible, and even if it is not possible to prevent aggregation or sedimentation, use a suspension agent that easily returns to the original suspension state. Efforts have been made to get it.

As one of the methods, it has been considered to prevent the particles from settling by reducing the dispersion particles, reducing the specific gravity of the dispersion particles and the dispersion medium, and increasing the viscosity of the dispersion medium. In such a case, in order to increase the viscosity of the dispersion medium, the concentration of the suspending agent such as a water-soluble polymer and / or the viscous agent is usually adjusted in the range of 0.2 to 5.0 w / v%. there were. However, even if the suspending agent and / or the thickening agent are within these concentration ranges, it is impossible to completely prevent the particles from settling, and the dispersed particles may settle and settle to cause caking and not be uniformly redispersed. It was a problem.

As another method, a method of increasing the particle size of the drug to improve the redispersibility is conceivable. However, when the particle size of the eye drop becomes large, discomfort or eye irritation occurs at the time of instillation, and in the case of nasal drop, If the particle size is large, it cannot be sprayed from the spray container. Furthermore, there is a drawback that the injection cannot be administered through an injection needle.

[0005] In recent years, many of the drugs exhibiting useful effects are poorly soluble drugs, and in order to supply them as aqueous solutions such as eye drops, nasal drops and injections, an aqueous suspension must be used. There are many cases where you don't get a reward. However, conventional aqueous suspensions have problems with redispersibility, and it is often difficult to obtain a liquid with a uniform concentration unless they are dispersed by shaking for a long time. A suspension was desired.

[0006]

SUMMARY OF THE INVENTION The present invention is to provide an aqueous suspension agent having good redispersibility which does not cause aggregation or caking of dispersed particles.

[0007]

In order to solve the above problems, the inventors of the present invention have conducted extensive studies and found that there is a certain relationship between the surface tension and redispersibility of an aqueous suspension. Found and completed the present invention. That is, the present invention relates to an aqueous suspension containing a water-soluble polymer in a concentration range in which the surface tension of the liquid agent starts to decrease and the surface tension stops decreasing, and a poorly soluble drug.

[0008]

BEST MODE FOR CARRYING OUT THE INVENTION As shown in Experimental Example 1 described below,
When the water-soluble polymer is added to the liquid agent, the surface tension of the liquid agent begins to decrease, and when the addition is continued, the decrease of the surface tension stops and the surface tension is kept almost constant. On the contrary, the dispersed particles of the aqueous suspension agent have good redispersibility from the time when the surface tension of the liquid agent starts to decrease by adding the water-soluble polymer, and the good redispersibility until the reduction of the surface tension stops. Is maintained. After that, when the reduction of the surface tension is stopped and a constant surface tension is maintained, the redispersibility of the dispersed particles gradually deteriorates. If the water-soluble polymer is not contained at all, the dispersed particles aggregate and float on the liquid surface, so that a uniform suspension agent cannot be prepared.

The concentration of the water-soluble polymer at which the surface tension of the liquid agent starts to decrease and the concentration of the water-soluble polymer at which the reduction of the surface tension of the liquid agent stops are usually contained in the poorly soluble drug used in the aqueous suspension agent. It increases depending on the amount, but it depends on the physical properties, chemical structure, concentration, particle size, etc. of the poorly soluble drug. Further, the concentration of the water-soluble polymer at which the surface tension of the liquid agent starts to decrease and the concentration of the water-soluble polymer at which the surface tension of the liquid agent stops decreasing are different depending on the type of the water-soluble polymer. The concentration of water-soluble polymer that begins to decrease is
Usually 0.00001-0.01 w / v%, especially 0.
The concentration of the water-soluble polymer is 0.0005 to 0.005 w / v%, and the concentration of the water-soluble polymer at which the decrease in the surface tension of the liquid agent stops is usually 0.0.
001 to 0.1 w / v%, especially 0.001 to 0.0
It is 1 w / v%. The water-soluble polymer of the aqueous suspension of the present invention is usually 0.00001 to 0.1 w / v%, preferably 0.00005 to 0.05 w / v%, more preferably 0.0001 to 0.01 w /. It can be prepared within the concentration range of v%. The ratio of the water-soluble polymer to the poorly soluble drug is usually 0.0001 to 0.2 part by weight, preferably 0.0005 to 0.1 part by weight, more preferably 0. It is 0005 to 0.05 parts by weight.

The water-soluble polymer used in the present invention may be of any kind as long as it is a pharmaceutically used water-soluble polymer. Among them, water-soluble cellulose derivatives and water-soluble polyvinyl polymers are preferred. Can be used for Examples of the water-soluble cellulose derivative include hydroxypropylmethylcellulose, methylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, and the like, with hydroxypropylmethylcellulose and methylcellulose being particularly preferred. Examples of the water-soluble polyvinyl polymer include polyvinylpyrrolidone K25, polyvinylpyrrolidone K30, polyvinylpyrrolidone K9.
0, polyvinyl alcohol (partially saponified product, complete saponified product) and the like.

The sparingly soluble drug used in the present invention is the term "slightly insoluble" in the Japanese Pharmacopoeia, which indicates the solubility.
It may have any of "insoluble", "extremely insoluble" and "almost insoluble" solubility, and includes all that is provided as an aqueous suspension when it is in the final formulation.

Specific examples of the poorly soluble drug used in the present invention include, for example, steroidal anti-inflammatory agents, anti-inflammatory and analgesic agents, chemotherapeutic agents, synthetic antibacterial agents, antiviral agents, hormone agents, anticataract agents, Examples include angiogenesis inhibitors, immunosuppressants, protease inhibitors, aldose reductase inhibitors and the like. Examples of the steroidal anti-inflammatory agent include cortisone acetate, hydrocortisone acetate, betamethasone, prednisolone, fluticasone propionate, dexamethasone, triamcinolone, loteprednol, fluorometholone, diflupredonate, mometasone furoate carboxylate, clobetasol propionate, divalerate acetate. Diflucortron, fluocinonide, amcinonide, halcinonide, fluocinolone acetonide, triamcinolone acetonide, flumethasone pivalate, clobetasone butyrate and the like can be mentioned. Examples of anti-inflammatory analgesics include alclofenac, aluminoprofen, ibuprofen, indomethacin, epirisol, oxaprozin, ketoprofen, diclofenac sodium, diflunisal, naproxen, piroxicam, fenbufen, flufenamic acid, flurbipfen, floctafenin, pentazocine, methiazinic acid, mefenamic acid, mefenamic acid. And so on. Examples of chemotherapeutic agents include salazosulfapyridine, sulfadimethoxine, sulfamethizole, sulfamethoxazole, sulfamethopyrazine, sulfa drugs such as sulfamonomethoxine, enoxacin, ofloxacin, sinoxacin, sparfloxacin, Cianphenicol,
Synthetic antibacterial agents such as nalidixic acid, tosufloxacin tosylate, norfloxacin, pipemidic acid trihydrate, pyromidic acid, fleroxacin, levofloxacin, antiviral agents such as acyclovir, ganciclovir, didanosine, zidovudine, vitarabine, itraconazole, ketoconazole, fluconazole, flucontocin. , Antifungal agents such as miconazole and pimalysin. Examples of the hormone agent include insulin zinc, testosterone propionate, estradiol benzoate and the like. Examples of the anti-cataract drug include pyrenoxine. Examples of angiogenesis inhibitors include fumagillin and its derivatives. Examples of the immunosuppressant include cyclosporine, rapamycin, tacrolimus and the like. Examples of the protease inhibitor include [L-3-trans-ethoxycarbonyloxirane-2-carbonyl] -L-leucine (3-methylbutyl) amide (E-64-d) and the like. Examples of the aldose reductase inhibitor include 5- (3-ethoxy-4-pentyloxyphenyl) thiazolidine-2,
4-dione and the like can be mentioned.

The concentration of the poorly soluble drug used in the present invention varies depending on the type of drug used, application, usage, etc., but is usually 0.01-10.0 w / v%, preferably 0.1-0.1%.
It is 5.0 w / v%.

The water-soluble suspension agent of the present invention contains a buffering agent (carbonate, phosphate, acetate, glutamic acid, in addition to a poorly soluble drug and a water-soluble polymer, as long as the surface tension is not changed.
Citrate, ε-aminocaproic acid, etc.), tonicity agent (glycerin, mannitol, sorbitol, propylene glycol, sodium chloride, potassium chloride, boric acid, etc.), stabilizer (sodium edetate, sodium citrate, etc.), Surfactants [polysorbate 80, polyoxyethylene (60) hydrogenated castor oil, tyloxapol, benzalkonium chloride, etc.], preservatives (paraoxybenzoates, benzalkonium chloride, benzethonium chloride, chlorobutanol, etc.), pH adjustment Known compounds such as agents (hydrochloric acid, sodium hydroxide, phosphoric acid, etc.) and other additives may be appropriately added.

When an additive that affects the surface tension of the aqueous suspension, such as a surfactant, is used, the surface tension is measured before blending the surfactant,
It is preferable to add the surfactant after determining the water-soluble polymer concentration. The pH of the aqueous suspension of the present invention is not particularly limited, but is usually 4 to 9, preferably 5 to
8 and it is preferred to determine the surface tension at the desired pH of the aqueous suspension.

The aqueous suspension of the present invention comprises eye drops, nasal drops,
It can be suitably used as an injection, an oral preparation, a lotion and the like.

The present invention will be described in more detail by the following test examples and examples, but the present invention is not limited thereto.

Test Example 1. Surface tension and redispersibility test [Method] 0.000001-0.5 w / v% of suspending agent
A solution having a concentration range of 1 was prepared, and a test drug was added to prepare an aqueous suspension. The surface tension of each aqueous suspension was measured using a Dinoy type surface tensiometer K122 (manufactured by Class Co.). Then, the mixture was filled in a 5 ml colorless polypropylene container, allowed to stand at 25 ° C. for 4 days, and then the container was rotated (60 rpm / minute) with a variable mix rotor VMR-5 (60 rpm, manufactured by Inai Co.) until redispersion. The time was measured. Moreover, the state of the dispersed particles was visually observed. The suspending agent is hydroxypropylmethyl cellulose [Metroses 60SH (TC-5E); manufactured by Shin-Etsu Chemical Co., Ltd., abbreviated as HPMC], methyl cellulose (Metroses SM-25; manufactured by Shin-Etsu Chemical Co., Ltd., M below).
Abbreviated as C), polyvinylpyrrolidone (K30; BA
Manufactured by SF Co., Ltd., hereinafter abbreviated as PVP) was used. The test drug is fluorometholone 0.05 w / v%, 0.1 w / v
%, Indomethacin 0.2 w / v%, 1.0 w / v% were used.

[Results] Relationship between the Surface Tension in Fluorometholone 0.1 w / v% Suspension and the Concentration of HPMC on Redispersion Time The relationship between the surface tension and redispersibility of fluorometholone 0.1 w / v% suspension The relationship is shown in FIG. HPMC is 0.00
The surface tension decreased from 01 w / v%, and the decrease of the surface tension almost stopped at 0.01 w / v%. On the other hand, HPMC is 0.
At 000005 to 0.0001 w / v%, the time required for redispersion was 2 seconds, but dispersed particles aggregated and floated, and a uniform suspension agent was not obtained. HPMC is 0.0001
At ~ 0.01 w / v%, the time required for redispersion was 4 seconds or less, the particles were quickly redispersed, and no aggregation of dispersed particles was observed, resulting in a uniform suspension agent. HPMC is 0.01
When w / v% or more, the time required for redispersion was 5 seconds or more, and it was found that redispersibility deteriorates. The suitable ratio of HPMC and fluorometholone was 0.001 to 0.1 part by weight to 1 part by weight of fluorometholone.

(2) Fluorometholone 0.05 w / v%
Relationship of HPMC Concentration on Surface Tension in Suspension HPMC was 0.0001 w / v% (surface tension; 65.1
The surface tension decreases from mN / m) to 0.002 w / v%
At (surface tension; 50.5 mN / m), the decrease in surface tension almost stopped. The redispersion time of fluorometholone in the concentration range was about 6 seconds, and the dispersion state was good. HPMC
The suitable ratio of the fluorometholone and the fluorometholone was 0.002 to 0.04 part by weight to 1 part by weight of the fluorometholone.

(3) Relationship between surface tension of fluorometholone 0.1 w / v% suspension and concentration of MC on redispersion time At a concentration of MC less than 0.0001 w / v%, surface tension is 72.5 mN / It was almost constant in m. MC is 0.00
The surface tension decreases from 01 w / v% and 0.01 w / v%
The surface tension was 54.5 mN / m, and the decrease in surface tension almost stopped. On the other hand, MC is 0.0001 w / v%
At the following concentrations, the time required for redispersion was 2 seconds or less, but dispersed particles aggregated and floated, and a uniform suspension agent was not obtained. In the concentration range of MC of 0.0001 to 0.01 w / v%, the time required for redispersion was 9 to 10.7 seconds, the particles were rapidly and uniformly dispersed, and no aggregation of dispersed particles was observed. It was also found that when the MC concentration was 0.01 w / v% or more, the time required for redispersion was close to 20 seconds, and redispersibility deteriorated. The preferred ratio of MC and fluorometholone is 0.001 with respect to 1 part by weight of fluorometholone.
Was 0.1 part by weight.

(4) Relationship between the surface tension of the indomethacin 0.2 w / v% suspension and the concentration of HPMC on the redispersion time. When the concentration of HPMC is 0.0001 w / v% or less, the surface tension is almost 72 mN / m. It was constant. HPMC is 0.
The surface tension decreases from 0001 w / v% to 0.01 w /
The surface tension at v% was 48 mN / m, and the decrease in surface tension almost stopped. On the other hand, HPMC is 0.0001w /
At a concentration of v% or less, the time required for redispersion was 7 seconds or less, but dispersed particles aggregated and floated, and a uniform suspension agent was not obtained. HPMC is 0.0001-0.01 w / v
%, The time required for redispersion is 6.3 to 8.
In 3 seconds, the particles were rapidly and uniformly dispersed, and no aggregation of dispersed particles was observed. It was also found that when the HPMC concentration was 0.01 w / v% or higher, the time required for redispersion was 12 seconds or longer, and the redispersibility deteriorated. The suitable ratio of HPMC and indomethacin was 0.0005 to 0.05 part by weight to 1 part by weight of indomethacin.

(5) Relationship between the surface tension of indomethacin 1.0 w / v% suspension and the concentration of HPMC on redispersion time At a concentration of HPMC of 0.0005 w / v% or less, the surface tension is 72.73 mN / m. Was almost constant. HPMC
Is 0.0005 w / v%, the surface tension is reduced to 0.0
The surface tension at 05 w / v% is 49.7 mN / m,
The decrease in surface tension almost stopped. On the other hand, HPMC is 0.
At a concentration of 0005 w / v% or less, the time required for redispersion was 7 seconds or less, but dispersed particles aggregated and floated, and a uniform suspension agent was not obtained. HPMC is 0.0005
In the concentration range of 0.005 w / v%, the time required for redispersion was 7.3 to 16 seconds, the particles were rapidly and uniformly dispersed, and no aggregation of dispersed particles was observed. Also, HPMC is 0.0
At a concentration of 05 w / v% or more, the time required for redispersion is 20
It was found that the redispersibility was deteriorated as the result was longer than a second. H
The suitable ratio of PMC and indomethacin was 0.0005 to 0.005 parts by weight with respect to 1 part by weight of indomethacin.

(6) Fluorometholone 0.05 w / v%
Relation of PVP concentration to surface tension in suspension PVP 0.0002 w / v% (surface tension; 72.3 m
The surface tension decreased from N / m) and the decrease of the surface tension almost stopped at 0.001 w / v% (surface tension; 69.5 mN / m). The suitable ratio of PVP and fluorometholone is 0.004 to 0.0 with respect to 1 part by weight of fluorometholone.
It was 2 parts by weight.

(7) Relationship between the concentration of PVP on the surface tension of fluorometholone 0.1 w / v% suspension When the concentration of PVP is 0.0003 w / v% or less, the surface tension is almost constant at 72.5 mN / m. Met. PVP is 0.
Surface tension decreases from 0003w / v%, 0.002w
The surface tension at 6 / v% was 69.5 mN / m, and the decrease in surface tension almost stopped. The redispersion time of fluorometholone in the concentration range was about 6 seconds, and the dispersion state was good. Further, it was found that when the concentration of PVP was 0.002 w / v% or more, the time required for redispersion was 18 seconds or more, and redispersibility deteriorated. The preferred ratio of PVP and fluorometholone is 0.
It was 003 to 0.02 parts by weight.

From the above results, the surface tension of the aqueous suspension varies depending on the type of the water-soluble polymer to be added, the type and concentration of the poorly soluble drug, but the surface tension is irrespective of the type of the water-soluble polymer. It was found that a suspension agent with good redispersion of a poorly soluble drug can be prepared within a concentration range where the decrease in surface tension stops from the concentration of the water-soluble polymer which begins to decrease.

Test Example 2. Redispersibility test under severe conditions [Method] The eye drops of Examples 2 and 4 described below were prepared,
Fill a 5 ml polypropylene container. 1 at 200G
After the suspension particles were settled by centrifugation for 0 minute, the container was rotated (60 rpm / minute) with a variable mix rotor VMR-5 (60 rpm, manufactured by Inai Co., Ltd.), and the time until redispersion was measured. [Results] The redispersion times of the eye drops of Examples 2 and 4 were 4 and 7 seconds, respectively. In the suspension agent after redispersion by visual observation, fine particles were uniformly dispersed. The above results show that the aqueous suspension of the present invention does not affect the redispersibility even under the severe conditions of forcibly settling suspended particles with a centrifuge, and it is also effective as a buffer or preservative. It turned out to be unaffected.

Example 1 Eye drops Fluorometholone 0.1 g Methylcellulose 0.0006 g Sodium chloride 0.85 g Disodium hydrogen phosphate dodecahydrate 0.1 g Benzalkonium chloride 0.005 g 0.1N hydrochloric acid Appropriate amount (pH 7) 0.0) Purified water 100 ml in total Purified water (about 80 ml) was heated to disperse methylcellulose and then cooled to room temperature to dissolve. Sodium chloride, disodium hydrogen phosphate dodecahydrate and benzalkonium chloride were added to and dissolved in this solution, and 0.1N hydrochloric acid was added to adjust the pH to 7. Add fluorometholone,
It was uniformly suspended by a homogenizer. Purified water was added to 100 ml to prepare a fluorometholone suspension ophthalmic solution.

Example 2 Eye Drops Fluorometholone 0.05 g Methylcellulose 0.00125 g Sodium Chloride 0.9 g Sodium Dihydrogen Phosphate Dihydrate 0.1 g Benzalkonium Chloride 0.005 g 0.1N Sodium Hydroxide (PH 7.0) 100 ml of purified water A fluorometholone suspension ophthalmic solution was prepared in the same manner as in Example 1.

Example 3 Eye drops Fluorometholone 0.02 g Methylcellulose 0.0001 g Sodium chloride 0.85 g Disodium hydrogen phosphate dodecahydrate 0.1 g Benzalkonium chloride 0.005 g 0.1N hydrochloric acid Appropriate amount (pH 7. 0) Purified water 100 ml in total As in Example 1, a fluorometholone suspension ophthalmic solution was prepared.

Example 4 Eye Drops Fluorometholone 0.05 g Polyvinylpyrrolidone K30 0.0015 g Sodium Chloride 0.9 g Sodium Dihydrogen Phosphate Dihydrate 0.1 g Benzalkonium Chloride 0.005 g 0.1N Sodium Hydroxide Appropriate amount (pH 7.0) Purified water 100 ml Total To about 80 ml of purified water, polyvinylpyrrolidone, sodium chloride, sodium dihydrogen phosphate dihydrate and benzalkonium chloride were added and dissolved. The pH was adjusted to 7 by adding 0.1N sodium hydroxide. Fluorometholone was added and ultrasonically suspended. Purified water was added to bring the total volume to 100 ml to prepare a fluorometholone suspension ophthalmic solution.

Example 5 Eye Drop Sulfamonomethoxine 0.1 g Hydroxypropylmethylcellulose 0.001 g Sodium Acetate 0.1 g Benzalkonium Chloride 0.005 g Sodium Chloride 0.9 g 0.1N Hydrochloric Acid Appropriate amount (pH 5.0) Purification Hydroxypropyl methylcellulose was heated and dispersed in about 100 ml of water and about 80 ml of purified water, and then cooled to room temperature to dissolve. Sodium chloride, sodium acetate and benzalkonium chloride were added to and dissolved in this solution, and 0.1N hydrochloric acid was added to adjust the pH to 5. Sulfamonomethoxine was added and uniformly suspended by a mill. Add purified water to 100
The volume was adjusted to ml to prepare a sulfamonomethoxine suspension eye drop.

Example 6 Nasal drops Hydrocortisone acetate 0.1 g Hydroxypropyl methylcellulose 0.0008 g Sodium dihydrogen phosphate 0.1 g Methyl paraoxybenzoate 0.026 g Propyl paraoxybenzoate 0.014 g Concentrated glycerin 2.6 g 0.1N Sodium hydroxide: Proper amount (pH 7.0) Purified water 100 ml Total To about 80 ml of purified water, methyl paraoxybenzoate and propyl paraoxybenzoate were heated and dissolved. After hydroxypropylmethyl cellulose was dispersed in this solution, it was cooled to room temperature and dissolved, and then concentrated glycerin and sodium dihydrogen phosphate were added and dissolved. The pH was adjusted to 7 by adding 0.1N sodium hydroxide. Hydrocortisone acetate was added and uniformly suspended by a mixer. Purified water was added to 100 ml to prepare a hydrocortisone acetate suspension nasal drop.

Example 7 Injection Estradiol benzoate 5.0 g Hydroxypropylcellulose 0.03 g Chlorobutanol 0.3 g Sodium chloride 0.9 g Purified water 100 ml Purified water About 80 ml was heated with chlorobutanol. Melted After hydroxypropyl cellulose was dispersed in this solution, it was cooled to room temperature and dissolved. Sodium chloride was added and dissolved, estradiol benzoate was added, and the mixture was uniformly suspended by a homogenizer. Add purified water 10
The suspension was adjusted to 0 ml to prepare an estradiol benzoate suspension injection.

Example 8 Oral drug Mefenamic acid 3.0 g Methylcellulose 0.01 g Sorbitol 20 g 5% ethyl paraoxybenzoate solution 1 ml Purified water 100 ml After dispersing methylcellulose in about 50 ml of purified water,
It was cooled to room temperature and melted. To this solution, sorbitol and a 5% ethyl paraoxybenzoate solution were added and dissolved. Mefenamic acid was added and uniformly suspended by a homogenizer. Purified water was added to 100 ml to prepare an estradiol benzoate suspension oral preparation.

Example 9 Lotion Agent Indomethacin 7.5 g Hydroxypropylcellulose 0.04 g dl Camphor 0.1 g Purified water Total 100 ml Disperse hydroxyprocellulose in about 50 ml of purified water, then cool to room temperature and dissolve. It was Dl camphor was added to this solution and dissolved. Indomethacin was added and ultrasonically suspended. Purified water was added to 100 ml to prepare an indomethacin suspension lotion.

[0037]

INDUSTRIAL APPLICABILITY Since the aqueous suspension of the present invention has good redispersibility, it can be used as an excellent aqueous suspension such as eye drops, nasal drops, injections, oral preparations and lotions.

[Brief description of drawings]

FIG. 1 is a graph showing the influence of H on surface tension and redispersion time in a 0.1 w / v% fluorometholone suspension in Test Example 1.
The relationship of the concentration of PMC is shown. -●-in the figure indicates the surface tension,
-◆-indicates redispersion time.

─────────────────────────────────────────────────── ─── Continuation of the front page (72) Inventor Katsuhiro Inada 1-3-401, 1-2-2 Ibukidaihigashi-cho, Nishi-ku, Kobe-shi, Hyogo (56) Reference JP-A-8-295622 (JP, A) 60-161915 (JP, A) JP-A-4-288013 (JP, A) JP-A-8-151332 (JP, A) JP-A-3-135924 (JP, A) (58) Fields investigated (Int .Cl. ⁷ , DB name) A61K 9/00-9/72 A61K 47/00-47/48 A61K 31/57

Claims (9)

(57) [Claims] 1. Fluorometholone and hydroxypropyl
Methylcellulose, methylcellulose, hydroxyethyl
From cellulose and hydroxypropyl cellulose
An aqueous suspension containing <br/> and at least one water soluble cellulose derivative selected, the concentration of water-soluble cellulose derivative is in the concentration range of 0.0001 to 0.01 w / v% An aqueous suspension agent having a good redispersibility of fluorometholone-dispersed particles, wherein the ratio of the fluorometholone to the water-soluble cellulose derivative is 0.0005 to 0.1 part by weight to 1 part by weight of fluorometholone. 2. Aqueous suspension according to claim 1, wherein the water-soluble cellulose derivative is hydroxypropyl methylcellulose or methylcellulose. 3. Aqueous suspension according to claim 1 or 2 is eye drops. 4. A nasal agent an aqueous suspension according to claim 1 or 2. 5. An aqueous suspension ophthalmic solution containing fluorometholone and hydroxypropylmethyl cellulose,
Hydroxypropyl methylcellulose is 0.0001-
Re-dispersion of fluorometholone-dispersed particles in the concentration range of 0.01 w / v% and the proportion of fluorometholone and hydroxypropylmethylcellulose being 0.0005 to 0.1 part by weight of hydroxypropylmethylcellulose to 1 part by weight of fluorometholone. Aqueous suspension eye drops with good dispersibility. 6. An aqueous suspension eye drop containing fluorometholone and methylcellulose, wherein methylcellulose is in a concentration range of 0.0001 to 0.01 w / v%.
In addition, the ratio of fluorometholone to methylcellulose is 0.001% by weight of methylcellulose to 1 part by weight of fluorometholone.
An aqueous suspension ophthalmic solution having good redispersibility of fluorometholone-dispersed particles in an amount of 05 to 0.1 part by weight. 7. Fluorometholone and hydroxypropyl
Methylcellulose, methylcellulose, hydroxyethyl
From cellulose and hydroxypropyl cellulose
In aqueous suspension containing a <br/> and at least one water soluble cellulose derivative is selected, from 0.0001 to 0.
Add the water-soluble cellulose derivative so as to be within the concentration range of 01 w / v%, and prepare so that the ratio of the water-soluble cellulose derivative is 0.0005 to 0.1 part by weight to 1 part by weight of fluorometholone. To improve the redispersibility of fluorometholone-dispersed particles in an aqueous suspension. 8. In an aqueous suspension of fluorometholone, hydroxypropylmethylcellulose is 0.00
In an aqueous suspension ophthalmic solution, the concentration of hydroxypropylmethylcellulose is adjusted to be 0.0005 to 0.1 part by weight to 1 part by weight of fluorometholone within a concentration range of 01 to 0.01 w / v%. Of improving the redispersibility of the fluorometholone-dispersed particles. 9. In an aqueous suspension of fluorometholone, methylcellulose is contained in an amount of 0.0001 to 0.01 w /
Redispersion of fluorometholone-dispersed particles in an aqueous suspension ophthalmic solution by adjusting the concentration of methylcellulose to 0.0005 to 0.1 part by weight per 1 part by weight of fluorometholone within the concentration range of v%. How to improve your sex.