CN114224830A - Single-dose bacteriostatic-free ophthalmic preparation and preparation method thereof - Google Patents
Single-dose bacteriostatic-free ophthalmic preparation and preparation method thereof Download PDFInfo
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- CN114224830A CN114224830A CN202111598808.0A CN202111598808A CN114224830A CN 114224830 A CN114224830 A CN 114224830A CN 202111598808 A CN202111598808 A CN 202111598808A CN 114224830 A CN114224830 A CN 114224830A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/08—Solutions
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/196—Carboxylic acids, e.g. valproic acid having an amino group the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0048—Eye, e.g. artificial tears
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
Abstract
The invention belongs to the technical field of medicines, and particularly relates to a single-dose bacteriostatic-free ophthalmic preparation and a preparation method thereof, wherein the single-dose bacteriostatic-free ophthalmic preparation comprises the following components in parts by weight: 2-amino-3-benzoylphenylacetic acid derivatives having anti-inflammatory effects; a nonionic polymeric thickener; an antioxidant; a stabilizer; a pH value regulator; water for injection; s1: dispersing polyvinylpyrrolidone and polyoxyethylene sorbitan fatty acid ester in water for injection; s2: dissolving boric acid, borax and edetate disodium in water for injection, and adding dispersed polyvinylpyrrolidone solution and polyoxyethylene sorbitan fatty acid ester solution; packaging in single-dose plastic vials under aseptic conditions. The invention adopts single-dose small bottle package, avoids the pollution of eye preparations to liquid medicine caused by repeated use, simultaneously, because of single use, bacteriostatic agents are not needed in the prescription, the use safety of patients and the medication adaptability of special patients are improved.
Description
Technical Field
The invention relates to the technical field of medicines, in particular to a single-dose bacteriostatic-free ophthalmic preparation and a preparation method thereof.
Background
Bromfenac sodium is a 2-amino-3-benzoylphenylacetic acid derivative, is a non-steroidal anti-inflammatory drug with anti-inflammatory activity, and has an action mechanism of inhibiting cyclooxygenase 1 and 2 so as to block the synthesis of prostaglandin which is an inflammatory mediator. Is suitable for symptomatic treatment of inflammatory diseases of external and anterior eyes (conjunctivitis, scleritis, and postoperative inflammation).
At present, the common ophthalmic preparation is a multi-dose ophthalmic preparation which can be repeatedly used after being opened, but the common ophthalmic preparation can be continuously used for many times, and the situations of liquid medicine bacterial contamination or cross infection of patients and the like often occur, which can affect the safety and the effectiveness of the ophthalmic preparation in the using process. In order to ensure that microorganisms are prevented from growing after the eye drops are unsealed, bacteriostatic agents meeting bacteriostatic efficacy requirements need to be added into prescription compositions of the multi-dose ophthalmic preparation, and researches on the bacteriostatic agents show that the problems of toxicity, narrow bacteriostatic spectrum and poor effect of the bacteriostatic agents added into eye drops. Common bacteriostatic agents such as benzalkonium chloride (benzalkonium chloride), which can damage corneal epithelium and cause degeneration of corneal endothelial cells, have significant inhibitory effect on the growth of fibroblasts cultured in vitro and inhibit the recovery of ocular surface.
In order to solve the problems, the invention provides a single-dose bacteriostatic-free ophthalmic preparation and a preparation method thereof.
Disclosure of Invention
Objects of the invention
In order to solve the problems, the invention provides a safe and effective single-dose bacteriostatic-free ophthalmic preparation and a preparation method thereof. The invention adopts single-dose small bottle package, avoids the pollution of eye preparations to liquid medicine caused by repeated use, simultaneously, because of single use, bacteriostatic agents are not needed in the prescription, the use safety of patients and the medication adaptability of special patients are improved.
(II) technical scheme
In order to solve the problems, the invention provides a single-dose bacteriostatic-free ophthalmic preparation which comprises the following components in parts by weight:
2-amino-3-benzoylphenylacetic acid derivatives having anti-inflammatory effects;
a nonionic polymeric thickener;
an antioxidant;
a stabilizer;
a pH value regulator;
water for injection.
Preferably, the 2-amino-3-benzoyl phenylacetic acid derivative with the anti-inflammatory effect is bromfenac sodium.
Preferably, the nonionic polymer thickener is composed of one or more of polyvinylpyrrolidone, sorbitan fatty acid ester, polyoxyethylene sorbitan fatty acid ester, and polyoxyethylene polyoxypropylene copolymer.
Preferably, the antioxidant is sodium sulfite.
Preferably, the stabilizer is edetate disodium.
Preferably, the pH value regulator is one or more of boric acid, borax, hydrochloric acid and sodium hydroxide.
Preferably, the composition comprises the following components in parts by weight: 0.9-1.1 parts of bromfenac sodium; 9-11 parts of boric acid; 9-11 parts of borax; 18-22 parts of polyvinylpyrrolidone; 1.35-1.65 parts of polyoxyethylene sorbitan fatty acid ester; 1.8-2.2 parts of anhydrous sodium sulfite; 0.18-0.22 parts of edetate disodium; 1000 parts of water for injection;
the pH value regulator is sodium hydroxide, and the pH value is regulated to 8.2-8.5.
Preferably, the composition comprises the following components in parts by weight: 270-330 parts of bromfenac sodium; 2970-3630 parts of boric acid; 2970-3630 parts of borax; 5400-6600 parts of polyvinylpyrrolidone; 405-495 parts of polyoxyethylene sorbitan fatty acid ester; 540-660 parts of anhydrous sodium sulfite; 54-66 parts of edetate disodium; 3-15 parts of benzalkonium chloride; 300000 parts of water for injection;
the pH value regulator is sodium hydroxide, and the pH value is regulated to 8.2-8.5.
A method for preparing a single dose of an ophthalmic formulation without bacteriostatic agent, comprising the following preparation steps:
s1: dispersing polyvinylpyrrolidone and polyoxyethylene sorbitan fatty acid ester in water for injection;
s2: dissolving boric acid, borax and edetate disodium in water for injection, and adding dispersed polyvinylpyrrolidone solution and polyoxyethylene sorbitan fatty acid ester solution;
s3: dissolving bromfenac sodium into the solution obtained in the step S2, fixing the volume, and adjusting the pH value of the solution to 8.2-8.5 by using sodium hydroxide;
s4: and (4) filtering the solution obtained in the step (S3) by using a 0.45-micron + 0.22-micron three-level filter element, then feeding the filtered solution into a three-in-one blowing and filling device, and filling the filled solution into a single-dose plastic vial under an aseptic condition to obtain the product.
Preferably, the preparation temperature of the S1-S4 is 20-50 ℃.
The technical scheme of the invention has the following beneficial technical effects:
the invention provides a safe and effective single-dose bacteriostatic-free ophthalmic preparation and a preparation method thereof. The invention adopts single-dose small bottle package, avoids the pollution of eye preparations to liquid medicine caused by repeated use, simultaneously, because of single use, bacteriostatic agents are not needed in the prescription, the use safety of patients and the medication adaptability of special patients are improved.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention will be described in further detail with reference to specific embodiments. It should be understood that the description is intended to be exemplary only, and is not intended to limit the scope of the present invention. Moreover, in the following description, descriptions of well-known structures and techniques are omitted so as to not unnecessarily obscure the concepts of the present invention.
Example 1
Prescription: 0.9g of bromfenac sodium, 9g of boric acid, 9g of borax, 18g of polyvinylpyrrolidone, 1.35g of polyoxyethylene sorbitan fatty acid ester, 1.8g of anhydrous sodium sulfite, 0.18g of edetate disodium, pH value adjustment of sodium hydroxide to 8.2, and addition of water for injection to 1000 ml.
The preparation method comprises the following steps: (1) dispersing polyvinylpyrrolidone and polyoxyethylene sorbitan fatty acid ester in water for injection at a temperature below 50 ℃, (2) dissolving boric acid, borax, disodium edetate and anhydrous sodium sulfite in the water for injection, and adding the dispersed polyvinylpyrrolidone solution and polyoxyethylene sorbitan fatty acid ester solution; (3) and (3) dissolving bromfenac sodium into the solution obtained in the step (2), fixing the volume, and adjusting the pH value of the solution to 8.2 by using sodium hydroxide to obtain the bromfenac.
Example 2
Prescription: 1.0g of bromfenac sodium, 10g of boric acid, 10g of borax, 20g of polyvinylpyrrolidone, 1.50g of polyoxyethylene sorbitan fatty acid ester, 2.0g of anhydrous sodium sulfite, 0.20g of edetate disodium, pH value adjustment of sodium hydroxide to 8.4 and addition of water for injection to 1000 ml.
The preparation method comprises the following steps: (1) dispersing polyvinylpyrrolidone and polyoxyethylene sorbitan fatty acid ester in water for injection at a temperature below 50 ℃, (2) dissolving boric acid, borax, disodium edetate and anhydrous sodium sulfite in the water for injection, and adding the dispersed polyvinylpyrrolidone solution and polyoxyethylene sorbitan fatty acid ester solution; (3) and (3) dissolving bromfenac sodium into the solution obtained in the step (2), fixing the volume, and adjusting the pH value of the solution to 8.4 by using sodium hydroxide to obtain the bromfenac.
Example 3
Prescription: 1.1g of bromfenac sodium, 11g of boric acid, 11g of borax, 22g of polyvinylpyrrolidone, 1.65g of polyoxyethylene sorbitan fatty acid ester, 2.2g of anhydrous sodium sulfite, 0.22g of edetate disodium, pH value adjustment of sodium hydroxide to 8.5, and addition of water for injection to 1000 ml.
The preparation method comprises the following steps: (1) dispersing polyvinylpyrrolidone and polyoxyethylene sorbitan fatty acid ester in water for injection at a temperature below 50 ℃, (2) dissolving boric acid, borax, disodium edetate and anhydrous sodium sulfite in the water for injection, and adding the dispersed polyvinylpyrrolidone solution and polyoxyethylene sorbitan fatty acid ester solution; (3) and (3) dissolving bromfenac sodium into the solution obtained in the step (2), fixing the volume, and adjusting the pH value of the solution to 8.5 by using sodium hydroxide to obtain the bromfenac.
Example 4
Prescription: 270g of bromfenac sodium, 2970g of boric acid, 2970g of borax, 5400g of polyvinylpyrrolidone, 405g of polyoxyethylene sorbitan fatty acid ester, 540g of anhydrous sodium sulfite, 54g of edetate disodium, sodium hydroxide for adjusting the pH value to 8.2, and adding 300L of water for injection.
The preparation method comprises the following steps: (1) dispersing polyvinylpyrrolidone and polyoxyethylene sorbitan fatty acid ester in water for injection at a temperature below 50 ℃, (2) dissolving boric acid, borax, disodium edetate and anhydrous sodium sulfite in the water for injection, and adding the dispersed polyvinylpyrrolidone solution and polyoxyethylene sorbitan fatty acid ester solution; (3) dissolving bromfenac sodium in the solution obtained in the step (2), fixing the volume, and adjusting the pH value of the solution to 8.2 by using sodium hydroxide; (4) and (3) filtering the solution obtained in the step (3) by using a 0.45 mu m +0.22 mu m three-stage filter element, then feeding the filtered solution into a three-in-one blowing and filling device, and filling the filled solution into a single-dose plastic vial under an aseptic condition to obtain the product.
Example 5
Prescription: 300g of bromfenac sodium, 3300g of boric acid, 3300g of borax, 6000g of polyvinylpyrrolidone, 450g of polyoxyethylene sorbitan fatty acid ester, 600g of anhydrous sodium sulfite, 60g of edetate disodium, pH value of sodium hydroxide is adjusted to 8.4, and 300L of water for injection is added.
The preparation method comprises the following steps: (1) dispersing polyvinylpyrrolidone and polyoxyethylene sorbitan fatty acid ester in water for injection at a temperature below 50 ℃, (2) dissolving boric acid, borax, disodium edetate and anhydrous sodium sulfite in the water for injection, and adding the dispersed polyvinylpyrrolidone solution and polyoxyethylene sorbitan fatty acid ester solution; (3) dissolving bromfenac sodium in the solution obtained in the step (2), fixing the volume, and adjusting the pH value of the solution to 8.4 by using sodium hydroxide; (4) and (3) filtering the solution obtained in the step (3) by using a 0.45 mu m +0.22 mu m three-stage filter element, then feeding the filtered solution into a three-in-one blowing and filling device, and filling the filled solution into a single-dose plastic vial under an aseptic condition to obtain the product.
Example 6
Prescription: 330g of bromfenac sodium, 3630g of boric acid, 3630g of borax, 6600g of polyvinylpyrrolidone, 495g of polyoxyethylene sorbitan fatty acid ester, 660g of anhydrous sodium sulfite, 66g of edetate disodium, sodium hydroxide for adjusting the pH value to 8.5, and adding 300L of water for injection.
The preparation method comprises the following steps: (1) dispersing polyvinylpyrrolidone and polyoxyethylene sorbitan fatty acid ester in water for injection at a temperature below 50 ℃, (2) dissolving boric acid, borax, disodium edetate and anhydrous sodium sulfite in the water for injection, and adding the dispersed polyvinylpyrrolidone solution and polyoxyethylene sorbitan fatty acid ester solution; (3) dissolving bromfenac sodium in the solution obtained in the step (2), fixing the volume, and adjusting the pH value of the solution to 8.5 by using sodium hydroxide; (4) and (3) filtering the solution obtained in the step (3) by using a 0.45 mu m +0.22 mu m three-stage filter element, then feeding the filtered solution into a three-in-one blowing and filling device, and filling the filled solution into a single-dose plastic vial under an aseptic condition to obtain the product.
Comparative example 1
Prescription: 300g of bromfenac sodium, 3300g of boric acid, 3300g of borax, 6000g of polyvinylpyrrolidone, 450g of polyoxyethylene sorbitan fatty acid ester, 600g of anhydrous sodium sulfite, 60g of edetate disodium, 3g of benzalkonium chloride, pH value of sodium hydroxide adjusted to 8.4, and 300L of water for injection.
The preparation method comprises the following steps: (1) dispersing polyvinylpyrrolidone and polyoxyethylene sorbitan fatty acid ester in water for injection at below 50 deg.C, and dispersing benzalkonium chloride in water for injection at below 50 deg.C; (2) dissolving boric acid, borax, disodium edetate and anhydrous sodium sulfite in water for injection, and adding dispersed polyvinylpyrrolidone solution, polyoxyethylene sorbitan fatty acid ester solution and benzalkonium chloride solution; (3) dissolving bromfenac sodium in the solution obtained in the step (2), fixing the volume, and adjusting the pH value of the solution to 8.4 by using sodium hydroxide; (4) and (4) filtering the solution obtained in the step (3) by using a 0.45 mu m +0.22 mu m three-stage filter element, then feeding the filtered solution into a three-in-one blowing and filling device, and filling the filled solution into a multi-dose plastic vial under an aseptic condition to obtain the multi-dose plastic vial.
Comparative example 2
Prescription: 300g of bromfenac sodium, 3300g of boric acid, 3300g of borax, 6000g of polyvinylpyrrolidone, 450g of polyoxyethylene sorbitan fatty acid ester, 600g of anhydrous sodium sulfite, 60g of edetate disodium, 9g of benzalkonium chloride, pH value of sodium hydroxide adjusted to 8.4, and 300L of water for injection.
The preparation method comprises the following steps: (1) dispersing polyvinylpyrrolidone and polyoxyethylene sorbitan fatty acid ester in water for injection at below 50 deg.C, and dispersing benzalkonium chloride in water for injection at below 50 deg.C; (2) dissolving boric acid, borax, disodium edetate and anhydrous sodium sulfite in water for injection, and adding dispersed polyvinylpyrrolidone solution, polyoxyethylene sorbitan fatty acid ester solution and benzalkonium chloride solution; (3) dissolving bromfenac sodium in the solution obtained in the step (2), fixing the volume, and adjusting the pH value of the solution to 8.4 by using sodium hydroxide; (4) and (4) filtering the solution obtained in the step (3) by using a 0.45 mu m +0.22 mu m three-stage filter element, then feeding the filtered solution into a three-in-one blowing and filling device, and filling the filled solution into a multi-dose plastic vial under an aseptic condition to obtain the multi-dose plastic vial.
Comparative example 3
Prescription: 300g of bromfenac sodium, 3300g of boric acid, 3300g of borax, 6000g of polyvinylpyrrolidone, 450g of polyoxyethylene sorbitan fatty acid ester, 600g of anhydrous sodium sulfite, 60g of edetate disodium, 15g of benzalkonium chloride, pH value of sodium hydroxide adjusted to 8.4, and 300L of water for injection.
The preparation method comprises the following steps: (1) dispersing polyvinylpyrrolidone and polyoxyethylene sorbitan fatty acid ester in water for injection at below 50 deg.C, and dispersing benzalkonium chloride in water for injection at below 50 deg.C; (2) dissolving boric acid, borax, disodium edetate and anhydrous sodium sulfite in water for injection, and adding dispersed polyvinylpyrrolidone solution, polyoxyethylene sorbitan fatty acid ester solution and benzalkonium chloride solution; (3) dissolving bromfenac sodium in the solution obtained in the step (2), fixing the volume, and adjusting the pH value of the solution to 8.4 by using sodium hydroxide; (4) and (4) filtering the solution obtained in the step (3) by using a 0.45 mu m +0.22 mu m three-stage filter element, then feeding the filtered solution into a three-in-one blowing and filling device, and filling the filled solution into a multi-dose plastic vial under an aseptic condition to obtain the multi-dose plastic vial.
The samples of example 5 and comparative example 2 are compared and investigated under the conditions of acceleration (40 ℃ +/-2 ℃, 25% RH +/-5% RH) and long-term (25 ℃ +/-2 ℃, 40% RH +/-5% RH), and the research result shows that the sample without the bacteriostatic agent in example 5 meets the requirements of all quality standards under the conditions of acceleration and long-term investigation, and can ensure the sterility in the shelf life and the quality of other products. The investigation result of the product added with the bacteriostatic agent in the comparative example 2 shows that the bacteriostatic agent has the tendency of decreasing along with the increase of the investigation time, but the bacteriostatic effect still meets the pharmacopoeia requirement within 24 months, but the change of the bacteriostatic dose can generate certain risk to the bacteriostatic effect to a certain extent. In summary, the bacteriostatic-free eye drops described in this patent reduce the risk of sterility in the course of use of the drug due to changes in the content and potency of the bacteriostatic agent. The results are shown in the following table.
NA is not applicable
The invention provides a safe and effective single-dose bacteriostatic-free ophthalmic preparation and a preparation method thereof. The invention adopts single-dose small bottle package, avoids the pollution of eye preparations to liquid medicine caused by repeated use, simultaneously, because of single use, bacteriostatic agents are not needed in the prescription, the use safety of patients and the medication adaptability of special patients are improved.
The foregoing shows and describes the general principles, essential features, and advantages of the invention. It will be understood by those skilled in the art that the present invention is not limited to the embodiments described above, and the preferred embodiments of the present invention are described in the above embodiments and the description, and are not intended to limit the present invention.
Claims (10)
1. A single-dose bacteriostatic-free ophthalmic preparation is characterized by comprising the following components in parts by weight:
2-amino-3-benzoylphenylacetic acid derivatives having anti-inflammatory effects;
a nonionic polymeric thickener;
an antioxidant;
a stabilizer;
a pH value regulator;
water for injection.
2. A single dose bacteriostatic agent-free ophthalmic formulation according to claim 1, wherein said anti-inflammatory 2-amino-3-benzoylphenylacetic acid derivative is bromfenac sodium.
3. The ophthalmic formulation of claim 1, wherein the non-ionic polymeric thickener is one or more of polyvinylpyrrolidone, sorbitan fatty acid ester, polyoxyethylene sorbitan fatty acid ester, and polyoxyethylene polyoxypropylene copolymer.
4. A single dose bacteriostatic free ophthalmic formulation according to claim 1 wherein said antioxidant is sodium sulfite.
5. The single dose bacteriostatic-free ophthalmic formulation according to claim 1, wherein said stabilizer is edetate disodium.
6. The ophthalmic preparation of claim 1, wherein the pH regulator is one or more selected from boric acid, borax, hydrochloric acid, and sodium hydroxide.
7. A single dose bacteriostatic agent-free ophthalmic formulation according to any one of claims 1 to 6, characterized by comprising the following components in parts by weight: 0.9-1.1 parts of bromfenac sodium; 9-11 parts of boric acid; 9-11 parts of borax; 18-22 parts of polyvinylpyrrolidone; 1.35-1.65 parts of polyoxyethylene sorbitan fatty acid ester; 1.8-2.2 parts of anhydrous sodium sulfite; 0.18-0.22 parts of edetate disodium; 1000 parts of water for injection;
the pH value regulator is sodium hydroxide, and the pH value is regulated to 8.2-8.5.
8. A single dose bacteriostatic agent-free ophthalmic formulation according to any one of claims 1 to 6, characterized by comprising the following components in parts by weight: 270-330 parts of bromfenac sodium; 2970-3630 parts of boric acid; 2970-3630 parts of borax; 5400-6600 parts of polyvinylpyrrolidone; 405-495 parts of polyoxyethylene sorbitan fatty acid ester; 540-660 parts of anhydrous sodium sulfite; 54-66 parts of edetate disodium; 3-15 parts of benzalkonium chloride; 300000 parts of water for injection;
the pH value regulator is sodium hydroxide, and the pH value is regulated to 8.2-8.5.
9. A method for preparing a single dose of an ophthalmic preparation without bacteriostatic agent, which is characterized by comprising the following preparation steps:
s1: dispersing polyvinylpyrrolidone and polyoxyethylene sorbitan fatty acid ester in water for injection;
s2: dissolving boric acid, borax and edetate disodium in water for injection, and adding dispersed polyvinylpyrrolidone solution and polyoxyethylene sorbitan fatty acid ester solution;
s3: dissolving bromfenac sodium into the solution obtained in the step S2, fixing the volume, and adjusting the pH value of the solution to 8.2-8.5 by using sodium hydroxide;
s4: and (4) filtering the solution obtained in the step (S3) by using a 0.45-micron + 0.22-micron three-level filter element, then feeding the filtered solution into a three-in-one blowing and filling device, and filling the filled solution into a single-dose plastic vial under an aseptic condition to obtain the product.
10. The method for preparing a single dose of an ophthalmic preparation without bacteriostatic agent according to claim 9, wherein the preparation temperature of S1-S4 is 20-50 ℃.
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2021
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| WO2019117252A1 (en) * | 2017-12-14 | 2019-06-20 | 参天製薬株式会社 | Eye drop containing 2-amino-3-(4-bromobenzoyl) phenylacetic acid or salt thereof |
| WO2021126874A1 (en) * | 2019-12-16 | 2021-06-24 | Sydnexis, Inc. | Ophthalmic compositions comprising d2o |
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