TWI243679B - Compositions including antibiotics and methods for using same - Google Patents

Abstract

Compositions including a quinolone component, such as ofloxacin, having fungistatic activity in the compositions, present in an amount effective as an antibiotic when the composition is placed in a mammalian eye, a NSAID component present in an amount to reduce inflammation or pain when the composition is placed in the eye, and a carrier component in an amount effective to act as a carrier for the quinolone component and NSAID component are provided. Methods of using the present compositions, for example, to resolve microbial infections and/or to reduce inflammation and/or pain in a mammalian eye are included within the scope of the present invention. Methods for treating corneal injuries are also included.

Description

1243679 A7 B7 V. Description of the Invention (i) The present invention relates to antibiotic-containing compositions and methods of using the same. More specifically, the present invention relates to an antibiotic-containing composition that can increase protection against tadpole contamination, reduce inflammation or pain, and / or can be used to treat corneal ulcers. Various antibiotic ingredients have been applied to the eye, for example, to control or treat or prevent eye infections and the like. In addition, antibiotic ingredients, such as tobramycin, have been suggested for use in combination with other materials, such as ophthalmia, and amphoteric non-steroidal anti-inflammatory drugs or NSAIDs. See, for example, ' Fu et al., U.S. Patent No. 5,414,010, the entire disclosure of which is incorporated herein by reference. Quinolones, such as uroxacin, have been used in compositions for treating eye infections. These antibiotic compositions include one or more additional ingredients that act as preservatives, such as benzyl alkali metal chloride (BAK) or organic mercury compounds. Antibiotic compositions, even in combination with preservatives, are sensitive to microbial properties, such as phytotoxicity. In addition, when a preservative-containing composition is administered to a patient, the preservative may cause irritation, allergic reactions, and / or other adverse side effects. Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs -I It I ^ ----------- (Please read the phonetic on the back? Matters before filling out this page). Therefore, if antibiotic compositions can be provided, And the use of these compositions, which can improve the protection against microbial contamination, and / or contain relatively low concentrations of preservatives will help. Corneal damage 'such as corneal ulcers and other corneal symptoms are contagious or may become contagious if left untreated, painful and sometimes require a long period of time to heal. If provided, for example, during the healing of these injuries,

This paper size applies the Chinese national standard (¾¾ (21Q x 297 Public Love J 1243679 A7 B7) V. Description of the invention (Combination of benefits to effectively alleviate the pain of these corneal injuries. Wanfa's summary description of the invention will be Novel antibiotic compositions have been found, such as: preferably, the human eye, and the :::: compounds of these compositions are applied to humans or animals' for example, to humans or animals; Shao, can provide Desired curative effect, such as m shellfish (eye biological infection, reducing inflammation and / or pain,:; =, irritation of the eyes and the like, etc.) In order to have improved anti-microbial properties, for example: _: protection ::: provides the user with the composition without greater assurance. This characteristic may allow the concentration of preservatives in the composition to be reduced, and therefore beneficial to reduce These adverse side effects are caused when the composition is administered to a patient. The composition can be easily manufactured, for example, using conventional techniques and can be conveniently used, for example, using traditional methods of administration. In one aspect of the present invention, the composition contains 4 kinds of Ruolong ingredients, an NSMD ingredient, and a carrier ingredient. The "Kueluo Long" ingredients exist as an effective amount of antibiotics when the composition is placed on the eyes of the dairy. In specific examples, the quinolonium component in the composition has bacteriostatic activity. That is, the quinolonium component in the composition has sufficient antibacterial properties or is active to substantially prevent the number of bacterial bacteria. Increased in other compositions. In fact, the presence of the hydrazone component in this composition is an effective preservative against the growth or staining of bacterium. The bacteriostatic activity of the effective quinolonium component present in the composition provides Benefits, for example, to explain elsewhere in this article, it is beyond the paper standard to apply the Chinese National Standard (CNS) A4 specification (〗 1G_X Norway Public Love 1243679 Printed by the Consumers ’Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs A7 V. Description of the invention (3 Expected and substantial. NSAID ingredients are present in an effective amount that reduces at least one of inflammation and pain by placing the composition in a mammalian eye. The carrier ingredient is used as a quinolonium ingredient in the composition An effective amount of a carrier of the NSAID component is present, and is preferably ocularly acceptable. The composition preferably contains a tritiated, more preferably a fluorinated quinolonium component. When the quinolonium component is Eurodol When using saxin ingredients, extremely useful compositions and results can be obtained. Although any NS AID ingredient can be used, the ingredients in this composition are preferably carboxyl (_C00H) NSAm ingredients. Even better, the NSAID ingredients Pyrrole Pyrrole, still better is Kentolac (ketorolac). This carrier component may contain one or more medicinal or ophthalmically acceptable materials such as: strength adjusting ingredients, buffer ingredients, viscosity ingredients, lubricating ingredients; interfacial activity Agent ingredients, preservative ingredients, and the like are conveniently used in the ophthalmic formulations. Preferably, the composition has a range of human physiology, for example, in the range of about 4 to about δ5. Two-in-one: can be in any form suitable for effective application to the human or animal being treated. For the best, the composition is selected from the group consisting of a solution, a body, an ointment, a solid, and other very effective ocular administration formulas. 2 = parts can be easily selected and / or synthesized to make the composition The method of presenting the desired use of such compositions includes the method of treating humans or animals, preferably Wu Yue <Qianwei. These amounts of the composition described herein. This == Therapeutic effective Shou Wan 忐 For the treatment of this paper based on these methods, discuss the outline J Ί --------------- ^ ---------. (Please (Please read the notes on the back before filling this page) 1243679 A7 B7 Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs 5. Description of the invention (4) The human or animal being treated provides one or more benefits. For example, these benefits include the prevention 'treatment or treatment of microbial infections, and the reduction of inflammation and / or pain. In another aspect of the invention, a method is provided for treating corneal damage to the eye. In this case, the term "corneal injury" refers to damage to the cornea that is infected with harmful and / or undesired microorganisms or that may become infected for an untreated period of time, for example, before the damage. Corneal ulcer is an example of corneal injury. These methods include administering a therapeutically effective amount of a composition to a mammalian eye with corneal damage, which contains a quinolonium component to be present as an effective amount of an antibiotic in a mammalian eye and an NSAID component in an effective amount to be mixed with The combination of swollen ingredients to alleviate the pain caused by corneal injury. Such a pain-reducing and antibiotic effect of the useful composition can reduce the discomfort of patients with corneal injury and promote or accelerate the healing of the injury. The useful composition preferably includes a carrier in the useful composition, which is present in an effective amount that can be used as a carrier for the p-quinolone component and the NS AID component. Any and all characteristics described herein and compositions of such characteristics are included in the scope of the present invention 'provided that the characteristics of any such composition do not contradict each other. These and other aspects and advantages of the present invention are described in the following detailed description and examples. Detailed description This composition contains a quinolonium ingredient, an NSAID ingredient, and a carrier ingredient. More preferably, the quinolonium component in the composition exhibits antibacterial properties. That is, it is preferred that the siruprol component in this composition has the size of this paper that is suitable for the Chinese National Standard (CNS) A4 (210 X 297 mm) — tll-llllm -------- ^ * — — — — — 1 — (Please read the notes on the back before filling this page) 1243679 A7

Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs

The sleepy activity can be used in the composition as a preservative against cold-spinning fungi. The mouthpieces of this group include an antibiotic effective amount of quinololone. The amount depends on, for example, the specific type of composition used, the specific composition used, the quinolones, and the specific characteristics of the composition. A w open application, the frequency of use of the composition and similar factors are quite wide Differences in scope. In many cases, the present composition can include quinolithone wounds with a sigmoidal circumference of 0.03% (w / v) or less to about 3% (w / v) or more. More preferably, the present composition includes a 4 Ruo Long component in an amount ranging from about (W / V) to about 0.5% (w / v) or about 1.1% (w / v). The 4 Ruolong component may be any Jun Ruolong derivative that is acceptable or suitable for her use in the eye and its antibiotic efficacy in the composition administered to mammalian eye parts is at least the basis of the 4 Ruolong—part Serving, preferably at least about 50%. Originally, quinolones can be derived from Junruolong itself or 4 Ruolong hydrates or acceptable salts of Junruolong, such as: including acid addition salts such as hydrogen chloride, cisbutadiene Acid esters, pamoates and the like, and alkali metal salts such as sodium and potassium salts, and = mixtures and the like. 〃 The composition includes an NSAID, which is present in an effective amount that reduces inflammation and / or pain when the composition is administered to mammalian eyes, for example, to prevent or treat the inflammatory process or pain caused, associated or accompanied Disease

The remaining symptoms include glaucoma, cystic edema, uveitis, diabetic A retinopathy, combined meningitis, or any injury caused by eye surgery or injury. The components of the NSAID may or may not include a carboxy (_coon) ring or moiety, or a derivatized group or moiety. In a specific example, the NSAID component ^ system = -9- This paper size applies the Chinese National Standard (CNS) A4 specification (21 × 297 mm) I ^ --- (Please read the precautions on the back before filling (This page) 1111!

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V. Description of the invention (9) Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs: and the pH range of acceptable acceptability, which is more preferably in the range of about 4 to about 10, and still more preferably about 6 to About 8, and especially about 6.8 to about 8. The surface-active ingredients to be used in the composition of the present invention include, but are limited to: lipoprotein cleaners, which when present in the composition, can reduce the surface strength between the combined pupae and the eye (tears) fluid. It is preferable to use a nonionic surfactant. As needed, the viscosity agent used in the composition of the present invention includes, but is not limited to, cellulose derivatives, such as: methyl methyl cellulose, #methyl fiber: sodium, polyethyl cellulose, other viscosity agents including available Substances and the like in ophthalmic formulations. ☆ If necessary, the lubricating ingredients of the composition of the present invention include, but are not limited to, polyvinyl alcohol, polyvinylpyrrolidone, carbopol, and the like. P. The antiseptic ingredients used in the composition of the present invention as needed include, but not limited to, horses: = BAK, organic mercury agents, such as: sodium ethylthiomersalate and acetic acid and phenylmercury nitrate, quaternary ammonium compounds, Methyl and propyl p-hydroxybenzene, benzyl alcohol, phenethyl alcohol and the like. Due to the antifungal activity of the cymbalone component of the composition, if the concentration of the preservative in the composition can be, and preferably reduced, the analogous composition Ingredients are not preservative of such bacteriostatic activity, but still have effective preservative power (for example: adequate preservative antibiotics that can pass applicable US and / or European preservative efficacy tests) are replaced by at least about 1 〇% or at least lower. Mouth products in this group may contain effective amounts of chelating or sequestering ingredients, such as ethylene diamine tetraacetate I (EDTA), citric acid, tartaric acid, and the like. — H. -------- Order --------- (Please read the notes on the back before filling out this page) 12- 1243679 A7 B7 10 V. Description of the invention (others, need to be used in The excipients in the composition include money agents, such as: anti-emulsification QI 1, such as: metal meta acid sulfite, ascorbic acid and the like. Eight types of h can be used in many types. In the specific example, The carrier component comprises a liquid, and the composition may be a solution or suspension. In another case, the carrier may simply contain water and one or more auxiliary ingredients as specified elsewhere herein. 2 The composition may be Any type that is effective for application to the eye. These types include: suspensions, ointments, colloids, solids, and the like. Ointments are intermediate between suspensions and colloids. These compositions of this composition may be It is prepared using techniques and procedures that are commonly known in this technology. In another specific example, the carrier component may be in the form of a transparent substance that forms a semi-solid "colloid" at human body temperature. Many are commonly used in this technology And :: know that different polymers are included here In order to make the composition gelatinous in the body, for example, it is possible to use an alkylene diamine-containing tetra-substituent (in about 40,000 / 0 to about 80/0 ethoxylated units and about 20% to about 6). 0% polyoxypropylene units replace the polymer system. The molecular weight of the polymer used is preferably at least about 7,000 and up to about 50%, more preferably between about 7, and about 30,000. If any colloid-forming component is present, it is present in an effective amount that enables the main colloid type of the mouth. For example, these colloid-forming components may account for about 10% or less of the total weight of the f 豊 component. It is present in a content range of about 50% or more. The composition may also be in the form of a solid insert, such as a solid dosage form suitable for insertion into a mammalian eye depression. For this purpose, the composition ingredient --r W-- I ---- I ---------- Order --------- (Please read the note on the back? Matters before filling out this page) Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs -13- 1243679 A7 printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs -----------_ §1 V. Description of the invention (12) Long ingredients for breastfeeding An effective amount of antibiotics can be present in the eyes and an NSAID component can be used in combination with an effective amount of Xiaojun Ruolong to reduce pain caused by corneal contusions. The pain relief and antibiotic effects of this useful composition can reduce corneal cornea Discomfort to injured patients and promote or accelerate injury &lt; healing. Corneal injuries include, but are not limited to, exfoliation, rupture, scratches, outside surgery, extraordinary or accidental injuries, bruises and similar corneal infections or may cause mammals Those suffering from pain. The useful corneal injury treatment composition preferably contains a carrier component, which is present in the useful composition in an effective amount as a quinolonium component and an NsAID component. The quinololone component, NSAID component and carrier component used to treat corneal injury are preferably the same as those described elsewhere herein. The useful composition can be in any suitable form effective for treating corneal injury, preferably in the same form as described elsewhere herein. This method of use &lt; may be considered therapeutic and / or preventive when used before surgery or after trauma occurs, before the microbiological sensation is extended, or until inflammation and / or pain occurs. The method used is effective in reducing the risk of these infections and reducing the severity of any worsening inflammation or pain. The method used in this method, including the generally used method and the method of treating corneal ulcer, may include any one of the compositions which can provide an effective amount to the mammalian eye &lt; an appropriate application step (one or more steps). These methods of application may include, but are not limited to, 'typical ocular application, instillation into the eye, placement of the insert in the depression (space) and the like between the eyeball and eyelid. Other common methods of applying the composition to the eye can be used, provided that the composition applied by this method can provide the desired benefits. This paper size applies Chinese National Standard &amp; NS) A4 specification (210 X 297 public love) -----. ^ T --------- (Please read the precautions on the back before filling this page) 1243679 A7

The dosage of the substance will of course depend on the specific active ingredients used due to t ′, the composition: the specific severity of the inflammation / pain / corneal ulcer used, and the nature: the degree of roll: should be determined. This dose and the measurement of the individual E of the treatment can be easily achieved by routine and well-known techniques in the following individual patients to achieve the desired results. The examples are illustrative of certain aspects of the invention. Group: 1 :::: — Mixed together to prepare compositions 1 to &quot; ... This temple composition has the following chemical composition. -16 The size of this paper is applicable to China National Standard (CNS) A4 (210 X 297 mm) --- --- Mo Yi --------------- ----- (Please read the precautions on the back before filling out this page) Oloxacin NaCl 0.6 w / v% 0.79 w / y% pH water composition 2 6.4 qs 100% Oloxacin 1.0 w / v % NaCl 0.79 w / v% pH 6.4 Aqueous composition 3 qs 100% Oloxacin 0.6 w / v% NaCl 0.3 w / v% EDTA 0.1 w / v% Boric acid 1.0 w / v% pH 6.4 Water qs 100% Economic Printed by the Consumer Property Cooperative of the Ministry of Intellectual Property Bureau 1243679 A7 B7 V. Description of the Invention (14) Printed Composition of the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs 4 Oroxacin 1.0 w / v% NaCl 0.3 w / v% EDTA 0.1 w / v% Boric acid 1.0 w / v% pH 6.4 Water composition 5 qs 100% Kentola 0.5 w / v% Oloxacin 0.6 w / v% NaCl 0.79 w / v% pH 6.4 Water composition 6 qs 100% Kent Roller 0.5 w / v% Oloxacin 1.0 w / v% NaCl 0.79 w / v% pH 6.4 Water composition 7 qs 100% Kentola 0.5 w / v% Oloxacin 0.6 w / v% NaCl 0.3 w / v% EDTA 0.1 w / v% boric acid 1.0 w / v% pH 6.4 Water qs 100% 11 ^-^ ---------------- Order --------- (Please read the precautions on the back before filling this page)- 17- This paper size applies Chinese National Standard (CNS) A4 (210 X 297 mm) 1243679 A7 B7 V. Description of the invention (15) Composition printed by employees' cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs 8 Kentola 0.5 w / v % Oroxacin 1.0 w / v% NaCl 0.3 w / v% EDTA 0.1 w / v% Boric acid 1.0 w / v% pH 6.4 Water composition 9 qs 100% Kentola 0.5 w / v% Oroxacin 0.3 w / v% NaCl 0.79 w / v% BAK 0.005 w / v% L-Arginine 0.28 w / v% pH 6.4 Aqueous composition 1 0 qs 100% Kentola 0.5 w / v% Oracoxacin 0.3 w / v % NaCl 0.79 w / v% BAK 0.005 w / v% METHOCEL® &gt; ⑴ 1 w / v% Carbopol ⑺ 0.2 w / v% pH 6.4 water-18- qs 100% --1 --- ^ ---- ------------ Order ----------------_--- t (Please read the precautions on the back before filling this page) This paper size Applicable to China National Standard (CNS) A4 specification (210 X 297 mm) 1243679 A7 —____ B7 V. Description of the invention (16) Composition 1 1 Oroxacin 0. 3 w / y% BAK 0.005 w / v% METHOCEL® ⑴ 0.1 w / v% Carbopol ⑺ 0.225 w / v% Glycerin 2.6 w / v% PH 6.5 Water qs 100% Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs (1 ) Methylcellulose (2) — a series of 2-propadienoic acid polymers cross-linked with pentitol. The individual simple preservative efficacy test of this composition uses S. aureus ATCC 6538 and A. niger ATCC 16404 as test strains. The test of this composition is compared with Ph Eur-A / B and USP standards according to ARM T_005. Take 10 ml of the individual composition and add about 105 cfu / ml of the test strain. At appropriate time intervals, Dey Engley's medium (DE) was used as a neutralizing medium to calculate the survival rate of bacteria and fungi. DE and filtration are sufficient to neutralize the antimicrobial substance in the composition. Dilute the sample in 9 ml to 9 ml in DE. Take 1 ml of this 1:10 dilution and filter through a 0.45 micron filter and wash with 100 ml of saline / TWEEN® 80. After washing the filter membrane again with 100 ml of saline / TWEEN (R) 80, the filtrate was placed on a TSA plate for bacteria and a SAB plate for fungi. The above steps can be used for the composition 1 1 (which is in the form of a colloid) except that the product is subjected to filtration before filtration. 丨 · 100— l ..---------- ΦM ---- l · --- Order --------- (Please read the notes on the back before filling out this page) -19- This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) A7 1243679 B7 Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs. 5. Dilution of the invention description (17) (0.1 ml of the product is added to the liter of DE). The results of these anti-corrosion efficacy tests are summarized as follows: Composition USP Ph Eur-A Ph Eur-B 1 Pass or fail to pass 2 Pass or fail to pass 3 Pass or fail to pass 4 Pass or fail 5 Pass or fail 6 pass no pass 7 pass pass barely pass 8 pass pass pass 9 pass pass 10 pass 11 pass pass Preservative efficacy test The detailed results are as follows: Composition 1 2 3 4 5 6 Test strain inoculation test period S. aureus ATTC 6538 4 xlO5 6 hours 2X 105 9X104 1X105 8X104 8x 104 1X105 24 hours 7X 104 3X104 6X104 &lt; 10 8X 103 2X103 7 days &lt; 10 &lt; 10 &lt; 10 1X101 &lt; 10 &lt; 10 14 days &lt; 10 &lt; 10 &lt; 10 &lt; 10 &lt; 10 &lt; 10 28 days &lt; 10 &lt; 10 &lt; 10 &lt; 10 &lt; 10 &lt; 10 A. niger ATCC 16404 lxlO5 7 days 8X104 8X104 4X103 1X103 7X104 7X104 14 days 2X 104 3X104 2X103 1X103 9X 104 9X104 28 days 1X104 3X104 2X103 8X102 2x 104 1X104 -20-(Please read the precautions on the back before filling this page) This paper Standards are applicable to China National Standard (CNS) A4 specifications (210 X 297 mm) 1243679 A7 B7 Printed Compositions of Employees' Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs 7 8 9 10 11 Test Strain Testing ----6 hours during inoculation period 1 X 1〇5 1 X 105 (&lt; 10 &lt; 10 &lt; 10 S. aureus 24 hours 3χ 103 1 X 104 &lt; 10 &lt; 10 &lt; 10 ATTC 6538 7 days &lt; 10 &lt; 10 &lt; 10 &lt; 10 \ 1 V / &lt; 10 4x 105 14 days &lt; 10 &lt; 10 &lt; 10 &lt; 10 &lt; 10 28 days &lt; 10 &lt; 10 &lt; 10 &lt; 10 &lt; 10 A. niger 7 days 2x 104 3X 103 1 X 101 &lt; 10 1 X 101 ATCC 16404 14 days 2x 104 7x 103 &lt; 10 &lt; 10 &lt; 10 1X105 28 days 4x 102 1X102 &lt; 10 &lt; 10 &lt; 1 V. Description of the invention ( 18) All compositions passed USPET very effectively. In particular, the fact that compositions 1 to 8 'did not contain ingredients known to have antiseptic properties passed unexpectedly through USPET, especially because the prior art compositions already included a quinolones such as urosaxin , Already includes preservatives, such as: BAK. In addition, Compositions 1 to 8 have sufficient anti-bacillus activity that can prevent the proliferation of A. niger. Therefore, the urosauron and urosaxin contained in these compositions have sufficient bacteriostatic activity as a preservative to prevent the composition from being contaminated by A. niger. Examples 1 2 to 2 3 Another series of compositions 12 to 24 were prepared by mixing different ingredients together. These compositions have the following chemical composition. Each composition includes a sufficient amount of water to make the total amount 100% by weight. Example number Concentration of active ingredient, w / v% 12 Ketorolac 0.5 Ofloxacin 0.3 NaCl 0.79 pH 6.4 -21-This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) ) 11J. -------- Order --------- (Please read the notes on the back before filling out this page) 1243679 Δ7 Α7 Β7 V. Description of Invention (19) Intellectual Property Bureau of the Ministry of Economic Affairs Employee Consumer Cooperative Co., Ltd. printed example number Active ingredient concentration, w / v% 13 Ketorolac 0.5 Ofloxacin 0.3 NaCl 0.30 EDTA 0.1 Boric acid 1.0 pH 6.4 14 Ketorolac 0.5 Ofloxacin 0.3 NaCl 0.79 BAK 0.005 pH 6.4 15 Ketorolac 0.5 Ofloxacin 0.3 NaCl 0.79 pH 7.4 16 Ketorloac 0.5 Ofloxacin 0.3 NaCl 0.79 BAK 0.005 pH 7.6 17 Ketorolac 0.5 Ofloxacin 0.3 NaCl 0.79 BAK 0.005 Octoxynol (3) 0.007 pH 6.4 -22- I ---- Leak ---------------- -Order --------- (Please read the notes on the back before filling in this page) This paper size is applicable to China National Standard (CNS) A4 (210 X 297 mm) A7 1243679 _B7 V. Description of the invention (20) Economy Intellectual Property Bureau Employee Consumer Cooperative Printed Example Number Active ingredient concentration, w / v% 18 Ketorolac 0.5 Ofloxacin 0.3 NaCl 0.79 BAK 0.005 Octoxynol (3) 0.007 pH 7.6 19 Ketorolac 0.5 Ofloxacin 0.3 NaCl 0.79 BAK 0.005 Cyclodextrin ⑷ 0.1 pH 6.4 20 Ketorolac 0.5 Ofloxacin 0.5 NaCl 0.79 BAK 0.005 Cyclodextrin (4) 0.1 pH 7.6 21 Ketorolac 0.5 Ofloxacin 0.3 NaCl 0.79 Purite (5) 0.007 pH 7.6 22 Ketorolac 0.5 Ofloxacin 0.3 NaCl 0.79 Purite (5) 0.007 Octoxynol (3) 0.007 pH 7.6 -23- --11 — ^ ---------------- Order --------- (Please read the notes on the back before filling this page) This paper size is applicable to China Standard (CNS) A4 specification (210 X 297 mm) Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economy 1243679 Δ7 Α7 __ Β7 V. Description of the invention (21) Example number Active ingredient concentration, w / v% 23 Ketorolac 0.5 Ofloxacin 0.3 NaCl 0.79 Purite (5) 0.007 Cyclodextrin (4) 0.1 pH 7.6 (3) Polyethylene glycol mono (butylphenyl) ether (4) 7-sulfobutyl ether-/?-Cyclodextrin ( 5) Stabilized chlorine dioxide. These samples were tested for corrosion resistance according to ARM T-005, against Ph Eur-A / B and USP standards. Take 10 ml of the sample and add about 105 cfu / mg of the test strain. Test strains include S. aureus ATCC 6538, P. aeruginosa ATCC 9027, E. coli ATCC 8739, C, albicans ATCC 10231, and A. niger ATCC 16404. At appropriate time intervals, DE was used as a neutralizing medium to analyze the survival of bacteria and tadpoles. DE, and filtering is sufficient to neutralize the antimicrobial substance in the composition. Dilute 1 ml of sample into 9 ml DE. 10 ml of the whole was filtered through a 0.45 micron filter and washed with 100 ml of phosphate buffered saline, pH 5.4. After washing the filter with 100 ml of phosphate buffered saline / TWEEN® 80 again, the filter was placed on a blood agar plate for bacteria and a SAB for maggots. The results are rounded off in the table below. -24- This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) —1 ^ — ^ --------------- Order ------- --------- 1— t (Please read the note 3 on the back before filling this page) 1243679 A7 V. Description of the invention (22 Printed sample number USP Ph Eur by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs -A Ph Eur-B 12 pass no pass no pass 13 pass no pass no pass 14 pass no pass 15 pass no pass 16 pass pass 17 pass pass 18 pass pass 19 pass no pass 20 pass pass 21 Pass or fail 22 Pass or fail 23 Pass or fail 23 The detailed results of the preservative efficacy test of compositions 12 to 17 are as follows Composition 12 13 14 15 16 17 Test strain inoculation amount test period S. aureus ATCC 6538 5X 105 6 hours 2 × 105 2x 105 4 3 × 105 &lt; 10 1 24 hours 2 × 105 2 × 105 &lt; 10 3x 105 &lt; 10 &lt; 10 7 days &lt; 10 2x 101 &lt; 10 &lt; 10 &lt; 10 &lt; 10 14 days &lt; 10 &lt; 10 &lt; 10 &lt; 10 &lt; 10 &lt; 1 0 28 days &lt; 10 &lt; 10 &lt; 10 &lt; 10 &lt; 10 &lt; 10 P. aeruginosa ATCC 9027 3x 105 6 hours &lt; 10 &lt; 10 &lt; 10 &lt; 10 &lt; 10 &lt; 10 24 hours &lt; 10 &lt; 10 &lt; 10 &lt; 10 &lt; 10 &lt; 10 7 days &lt; 10 2 × 101 &lt; 10 &lt; 10 &lt; 10 &lt; 10 14 days &lt; 10 &lt; 10 &lt; 10 &lt; 10 &lt; 10 &lt; 10 28 days &lt; 10 &lt; 10 &lt; 10 &lt; 10 &lt; 10 &lt; 10 -25---------------------- ^ --------- Φ (Please read the precautions on the back before filling this page) This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) 1243679 A7 B7 Intellectual Property of the Ministry of Economic Affairs Bureau Consumer Consumption Cooperative Printed Composition 12 13 14 15 16 17 Test strain inoculation volume E. coli ATCC 8739 5x 105 6 hours 6x 101 5X101 &lt; 10 5X 101 &lt; 10 — ~~ — &lt; 10 24 hours 5X 102 &lt; 10 &lt; 10 &lt; 10 &lt; 10 &lt; 10 7 days &lt; 10 &lt; 10 &lt; 10 &lt; 10 &lt; 10 &lt; 10 14 days &lt; 10 &lt; 10 &lt; 10 &lt; 10 &lt; 10 ------ &lt; 10 28 days &lt; 10 &lt; 10 &lt; 10 &lt; 10 &lt; 10 &lt; 10 C. albicans ATCC 10231 3x 105 7 days 1X105 2X105 &lt; 10 3x 105 &lt; 10 &lt; 10 14 days 1X105 2X105 &lt; 10 1X105 &lt; 10 &lt; 10 &lt; 10 ΤχΤ〇ϊ ^ 28 days 8X104 9X104 &lt; 10 9X104 &lt; 10 A. niger ATCC 16404 1X105 7 days 6X104 6X104 3X101 7X 104 &lt; 10 — 14 days 4X 104 3X104 4 6X 104 1X102 &lt; 10 28 days 3x 104 3X104 &lt; 10 5X104 &lt; 10 &lt; 10 — V. Description of the invention (23 All compositions passed USPET. Compositions 12 to 15 do not contain ingredients known to have a preservative effect. Although compositions 12 and 15 did not pass the European preservative efficacy test, they did have anti-bacillus activity to prevent the proliferation of C. albicans and A, niger. The quinololon and urosaxin contained in these compositions have bacteriostatic activity as a preservative of the composition to prevent the contamination of C .. albicans &amp; Example 2 4 to 4 1 Compositions 5 to 10 and 12 to 23 were both applied to the human eye that had suffered surgical injury. Before the application, each pair of eyes developed some degree of inflammation and it was the source of some degree of pain. Each solution composition is applied to the eye in an amount of about 1 to 2 drops per eye, each drop containing about 25 to 50 microliters. Apply 3 to 4 times daily. Each of the colloidal compositions is applied 3 to 4 times a day by placing about 500 to 100 microliters of the composition between the eyelids and the eyeballs. _ _ -26- This paper size applies to China National Standard (CNS) A4 (21〇X 297 public love) in! --------------- Order ------ --- ΜΨ (Please read the note on the back? Matters before filling out this page) 1243679

V. Description of the invention (24) After one week of such application, each and every treated eye has no inflammation and is not a source of pain. In addition, each eye is still free of microbial infections. ^ JH4 2 &gt; 5 9 Compositions 5 to 10 and 12 to 23 were applied to the eyes of a human who had suffered a surgical injury. Before the application, each pair of eyes developed some degree of inflammation and it was the source of some degree of pain. Each solution composition is applied to the eye in an amount of about 1 to 2 drops per eye, each drop containing about 25 to 50 microliters. Apply once every 30 minutes. Each of the colloidal compositions is applied every 30 minutes by placing about 50 to 100 microliters of the composition between the eyelid and the eyeball. Within a day of starting the application, the pain caused by corneal ulcers was substantially reduced. After two weeks of such application, all corneal ulcers were substantially cured and no more pain was felt at the ulcers. In addition, each eye remains free of microbial infections. Although the present invention has been described with regard to various specific examples and specific examples, it should be understood that the present invention is not limited thereto and that it can perform various exercises within the scope of the following patent applications. — 11 — ^ --------------- Order --------- ^^ 1 (Please read the notes on the back before filling out this page) Intellectual Property Bureau, Ministry of Economic Affairs Printed by Employee Consumer Cooperatives -27- This paper

Claims (1)

A B c D Chinese Patent Application No. 12187 Amendment to the Chinese Patent Application Range (May 91) VI. Patent Application Sentence 6 1. A pharmaceutical composition for treating mammalian eyes, which contains as an active ingredient: If a quinolone component is present in an amount of 0.03 to 3% w / v, the quinolonium component in the composition has antifungal activity, and an NSAID component, which has a content of 0.0001% w / v V 彡 10% W / v is present; and an ophthalmically acceptable carrier component. 2. The pharmaceutical composition according to item 1 of the scope of patent application, wherein the NSAID component is an NS AID component containing several bases. 3. The pharmaceutical composition according to item 1 of the scope of patent application, wherein the carrier component is selected so that the composition exhibits a type selected from the group consisting of a solution, a suspension 'colloid' paste and a solid. 4 · The pharmaceutical composition according to item 1 of the scope of the patent application, in which the 4 Ruolong ingredients are painted and drawn. 5. The pharmaceutical composition according to item 4 of the scope of patent application, wherein the NS AID component is a NSAID component containing a carboxyl group. 6. The pharmaceutical composition according to item 1 of the scope of patent application, wherein the quinolonium component is a fluorinated quinolonium component. 7 ♦ The pharmaceutical composition according to item 6 of the scope of patent application, wherein the NSAID component is a NSAID component containing a carboxyl group. 8. The pharmaceutical composition according to item 1 of the scope of the patent application, in which p-Quiron is a type of ofioxacin. 9. The pharmaceutical composition according to item 8 of the scope of the patent application, in which the NS AID is applied to the national standard of country f (c μ specification (21〇χ297297) 1243679 Ingredients are NS AID ingredients containing carboxyl groups. Among them, NSAID is selected among them, suspension, glue, among which quinolonium is formed, among them, quinolonium, among which quinolonium 10. The pharmaceutical composition according to item 1 of the scope of patent application, the ingredients are ketorolac ingredients. 1L According to the pharmaceutical composition under the scope of the patent application No. 10, the body composition can make the composition exhibit a type selected from the group consisting of a solution 'T shape and a solid. 12. The pharmaceutical composition according to item 10 of the scope of the patent application, the portion is a self-chemicalized quinolonium ingredient. 13. The composition of the pharmaceutical composition according to item 10 of the scope of patent application is a fluorinated quinolonium component. 14. The composition of the pharmaceutical composition according to the scope of the patent application No. 丨 0 The ingredient is an oxalicin ingredient. 15. Root pain According to the pharmaceutical composition in the first patent application scope, 1 Dan provides effective antibiotics in mammalian eyes σ, and reduces inflammation and pain in mammalian eyes. Its inflammation or pain in mammalian eyes 16, according to the patent application. The pharmaceutical composition of scope item 3 can provide effective antibiotics and reduce mammalian eye pain. 0 Π. According to the patent application of scope of claim 4, the pharmaceutical composition can provide effective antibiotics in mammalian eyes and reduce mammalian eye area. Inflammation or pain. 18, The pharmaceutical composition according to item 8 of the scope of patent application, which can provide effective antibiotics in mammalian eyes, and reduce inflammation or pain in mammalian eyes 0 -2- 1243679 A8 B8-C8 ------ 19. According to the pharmaceutical composition of item 10 of the scope of claim, it can provide effective antibiotics in mammalian eyes and reduce inflammation or pain in mammalian eyes. &amp; — '20. According to: The pharmaceutical composition according to item 14 of the patent, which can promote the supply of effective biotin in mammalian eyes and reduce inflammation or pain in mammalian eyes. ^; A pharmaceutical composition for reducing eye pain in mammals, which contains a quinolonium ingredient as an active ingredient, which is present in an amount of 0.03: ^ v to 30 / 〇W / V, and an NSAID ingredient, It is present in an amount of 0.001% ~ / 乂 to 10%; ¥ ~. 22. The pharmaceutical composition according to claim 21, wherein the quinolonium component in the composition has antifungal activity. 23. The pharmaceutical composition according to item 21 of the application, wherein the quinolonium component is a quinolonium component. 24. The pharmaceutical composition according to item 2 of the patent application scope, wherein the quinolonium component is a fluorinated quinolonium component. 25. The pharmaceutical composition according to item 21 of the scope of patent application, in which the content of $ Ruolong is oroxacin. 26. The pharmaceutical composition according to item 21 of the application, which is a NS AID component containing a carboxyl group. 27. The pharmaceutical composition according to item 2i of the patent application scope, wherein &lt; nsaid is a Kentvila ingredient. 28. The pharmaceutical composition according to the scope of application for item 25, wherein iNSAID is a kind of Kentrola ingredient. -3-This paper size is in accordance with Chinese National Standard (CNS) A4 (210 X 297 mm) AB c D 1243679 6. Application for patent scope 29 · —A pharmaceutical composition for treating corneal injury, which contains a quinoline Long component 'which is present in an amount of 0.3% w / v to 3% w / v, and an NSAID component which is present in an amount of 0.00lw / v to 10% w / v. 30. The pharmaceutical composition according to item 29 of the patent application, wherein the corneal injury is a corneal ulcer. 31. The pharmaceutical composition according to item 29 of the patent application scope, wherein the quinolonium component is a quinolonium component. 32. The pharmaceutical composition according to item 29 of the scope of application for patents, wherein the π-quinolone formation is a fluorinated α-quinolone component. 33. The pharmaceutical composition according to item 29 of the scope of application for patent, wherein the quinolonium component is uroxacin. 34. The pharmaceutical composition according to item 33 of the scope of patent application, wherein the corneal injury is a corneal ulcer. 35. The pharmaceutical composition according to item 29 of the application, wherein the NSAID is a NS AID component containing a carboxyl group. 36. The pharmaceutical composition according to item 29 of the application, wherein the NS AID is a Kentrola ingredient. 37. The pharmaceutical composition according to item 36 of the application, wherein the corneal injury is a corneal ulcer. 38. The pharmaceutical composition according to item 33 of the application, wherein the NS AID is a Kentola ingredient. 39. The pharmaceutical composition according to item 38 of the patent application, wherein the corneal injury is a corneal ulcer. -4- This paper size is applicable to China National Standard (CNS) A4 (21〇 x 297mm)