CN113712908A - Composition for treating allergic conjunctivitis and preparation method thereof - Google Patents
Composition for treating allergic conjunctivitis and preparation method thereof Download PDFInfo
- Publication number
- CN113712908A CN113712908A CN202010446780.8A CN202010446780A CN113712908A CN 113712908 A CN113712908 A CN 113712908A CN 202010446780 A CN202010446780 A CN 202010446780A CN 113712908 A CN113712908 A CN 113712908A
- Authority
- CN
- China
- Prior art keywords
- cetirizine hydrochloride
- regulator
- pharmaceutical composition
- preservative
- parts
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Classifications
-
- 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
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
-
- 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
- A61K47/34—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
-
- 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
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61K47/38—Cellulose; Derivatives thereof
-
- 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
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
Abstract
The invention relates to the technical field of ophthalmic medicines, in particular to a composition for treating allergic conjunctivitis and a preparation method thereof, wherein the composition comprises the following components in parts by weight: 0.1-0.5% of cetirizine hydrochloride, an osmotic pressure regulator, a thickening agent, 4-8% of a pH regulator and 0.010.02% of a preservative; the above components have a pH of 7.0 to 7.8 and an osmolality of 280 to 310 mOsmol/kg. The invention effectively solves the problem of the compatibility of benzalkonium chloride and a plastic bottle in the existing cetirizine hydrochloride eye drops, related substances are obviously superior to the existing cetirizine hydrochloride eye drops, and the long-term stability is better; the consumption of the preservative is less, the environment is protected, and the consumption is low; the use population of contact lens patients is increased, and the medication compliance is increased.
Description
Technical Field
The invention relates to the technical field of ophthalmic medicines, and in particular relates to a cetirizine hydrochloride aqueous pharmaceutical composition and a preparation method thereof.
Background
The cetirizine hydrochloride eye drop original research reagent is sold as ZERVIATE, and is an ophthalmic medicine developed by Alcon company for relieving allergic conjunctivitis. The bacteriostatic agent used in the ZERVIATE is 0.01 percent of benzalkonium chloride, which belongs to quaternary ammonium surfactants, has moderate bactericidal strength, strong effect on gram-positive bacteria and no effect on pseudomonas aeruginosa, acid-fast bacillus and bacterial spores.
Benzalkonium chloride can cause allergic conjunctivitis, hypopsia, contact dermatitis, etc. Patients suffering from glaucoma, dry eye, infection and iritis are exposed to benzalkonium chloride containing eye drops too often and too long to cause damage. Their incidence of endothelial damage, epithelial edema and bullous keratopathy is high and, due to the severity of these diseases, may lead to neglect other minor hazards, especially in patients with epithelial defects or corneal ulceration.
Benzalkonium chloride has incompatibility with anionic surfactants, high concentrations of nonionic surfactants, hydrogen peroxide, aluminum metal, iodides, silver salts, nitrates, citrates, cotton, proteins, lanolin, fluorescein, zinc oxide, zinc sulfate, manganic acid, salicylic acid, hypromellose, kaolin, soaps, sulfa drugs, some rubber mixes, and some plastic mixes. The plastic bottles used for ZERVIATE also have the potential risk of reacting with benzalkonium chloride.
The notes in the ZERVIATE Specification clearly indicate that patients wearing contact lenses, if the eyes are congested, are advised not to wear contact lenses during the treatment period with the drug, because the preservative benzalkonium chloride in the drug can be absorbed by soft contact lenses. Patients who wear soft contact lenses and who are not engorged with eye are unable to reapply the contact lenses after at least 10 minutes of dropping the medication. The eye irritation symptoms caused by contact lenses cannot be treated with the present drug.
Disclosure of Invention
The invention provides a cetirizine hydrochloride aqueous pharmaceutical composition and a preparation method thereof in order to make up for the defects of the prior art.
The invention is realized by the following technical scheme:
a cetirizine hydrochloride aqueous pharmaceutical composition, which is characterized in that: comprises the following components in parts by weight: 15-18 parts of cetirizine hydrochloride, 50-55 parts of osmotic pressure regulator, 50-55 parts of thickening agent, 8-11 parts of pH regulator and 0.01-0.02 part of preservative; the above components have a pH of 7.0 to 7.8 and an osmolality of 250 to 290 mOsmol/kg.
Wherein the osmotic pressure regulator is sodium chloride.
Wherein the pH regulator is edetate disodium.
Wherein the preservative is polyhexamethylene biguanide.
Wherein the thickening agent is hydroxypropyl methylcellulose.
The specific formula is as follows:
the preparation method of the cetirizine hydrochloride aqueous pharmaceutical composition comprises the following steps:
(1) firstly, sequentially adding a pH regulator, an osmotic pressure regulator and cetirizine hydrochloride into a proper amount of water, and continuously stirring until the pH regulator, the osmotic pressure regulator and the cetirizine hydrochloride are dissolved;
(2) adding the thickening agent into a proper amount of water, continuously stirring until the thickening agent is uniformly dispersed, and adding the preservative;
(3) mixing the two solutions and then continuously stirring; dropwise adding sodium hydroxide to adjust the pH of the solution to 7.45, and then supplementing enough water for injection;
(4) packaging with lid after subpackaging.
The invention has the beneficial effects that: the polyhexamethylene biguanide has a wide application range, but is not reported as a bacteriostatic agent of eye drops. The invention effectively solves the problem of the compatibility of benzalkonium chloride and a plastic bottle in the existing cetirizine hydrochloride eye drops, related substances are obviously superior to the existing cetirizine hydrochloride eye drops, and the long-term stability is better; the consumption of the preservative is less, the environment is protected, and the consumption is low; the use population of contact lens patients is increased, and the medication compliance is increased. The invention also contains hydroxypropyl methylcellulose, which obviously improves the bacteriostatic effect of polyhexamethylene biguanide, and the drug combination leads the related substances to be obviously superior to the existing cetirizine hydrochloride eye drops, and has better long-term stability.
(IV) detailed description of the preferred embodiments
Example 1
Comprises the following components:
cetirizine hydrochloride 0.24 w/v%, edetate disodium 0.1 w/v%, sodium chloride 0.5 w/v%, polyhexamethylene biguanide 0.0001 w/v%, sodium hydroxide pH adjusted to 7.45, adding water for injection to volume 100%;
the cetirizine hydrochloride eye drops prepared according to the proportion comprises the following specific steps:
firstly, adding edetate disodium, stirring and dissolving, then adding polyhexamethylene biguanide, and continuously stirring;
adding sodium chloride into the solution, and stirring until the sodium chloride is dissolved;
adding cetirizine hydrochloride, and continuously stirring until the cetirizine hydrochloride is completely dissolved;
and fourthly, dropwise adding sodium hydroxide to adjust the pH value of the solution to 7.45, and then supplementing the solution to a sufficient amount of water for injection.
And fifthly, covering and packaging after subpackaging.
Example 2
Comprises the following components:
cetirizine hydrochloride 0.24 w/v%, edetate disodium 0.1 w/v%, sodium chloride 0.5 w/v%, polyhexamethylene biguanide 0.0002 w/v%, sodium hydroxide pH adjusted to 7.45, adding water for injection to 100% volume;
the preparation method is the same as that of example 1.
Example 3
Comprises the following components:
cetirizine hydrochloride 0.24 w/v%, edetate disodium 0.1 w/v%, sodium chloride 0.55 w/v%, polyhexamethylene biguanide 0.0001 w/v%, sodium hydroxide pH adjusted to 7.45, adding water for injection to volume 100%;
the preparation method is the same as that of example 1.
Example 4
Comprises the following components:
cetirizine hydrochloride 0.24 w/v%, edetate disodium 0.1 w/v%, sodium chloride 0.55 w/v%, polyhexamethylene biguanide 0.0002 w/v%, sodium hydroxide pH adjusted to 7.45, adding water for injection to 100% of volume;
the preparation method is the same as that of example 1.
Example 5
Comprises the following components:
cetirizine hydrochloride 0.24 w/v%, edetate disodium 0.1 w/v%, sodium chloride 0.5 w/v%, hypromellose poly 0.5 w/v%, polyhexamethylene biguanide 0.0001 w/v%, sodium hydroxide pH adjusted to 7.45, and water for injection added to 100% of volume;
the cetirizine hydrochloride eye drops prepared according to the proportion comprises the following specific steps:
firstly, sequentially adding disodium edetate, sodium chloride and cetirizine hydrochloride into a proper amount of water, and continuously stirring until the disodium edetate, the sodium chloride and the cetirizine hydrochloride are dissolved;
secondly, adding hydroxypropyl methylcellulose into a proper amount of water, continuously stirring until the hydroxypropyl methylcellulose is uniformly dispersed, and then adding polyhexamethylene biguanide;
mixing the two solutions and then continuously stirring; sodium hydroxide is added dropwise to adjust the pH of the solution to 7.45, and then sufficient water for injection is added.
Fourthly, the mixture is packaged with a cover after being subpackaged.
Example 6
Comprises the following components:
cetirizine hydrochloride 0.24 w/v%, edetate disodium 0.1 w/v%, sodium chloride 0.5 w/v%, hypromellose poly 0.5 w/v%, polyhexamethylene biguanide 0.0002 w/v%, sodium hydroxide pH adjusted to 7.45, adding water for injection to 100% of volume;
the preparation method is the same as in example 5.
Example 7
Comprises the following components:
cetirizine hydrochloride 0.24 w/v%, edetate disodium 0.1 w/v%, sodium chloride 0.55 w/v%, hypromellose poly 0.5 w/v%, polyhexamethylene biguanide 0.0001 w/v%, sodium hydroxide pH adjusted to 7.45, and water for injection added to 100% of volume;
the preparation method is the same as in example 5.
Example 8
Comprises the following components:
cetirizine hydrochloride 0.24 w/v%, edetate disodium 0.1 w/v%, sodium chloride 0.55 w/v%, hypromellose poly 0.5 w/v%, polyhexamethylene biguanide 0.0002 w/v%, sodium hydroxide pH adjusted to 7.45, and water for injection added to 100% of volume;
the preparation method is the same as in example 5.
Comparative example 1
Cetirizine hydrochloride 0.24 w/v%, edetate disodium 0.1 w/v%, sodium chloride 0.55 w/v%, polyhexamethylene biguanide 0.001 w/v%, sodium hydroxide pH is adjusted to 7.45, and water for injection is added to the volume of 100%;
the preparation method is the same as that of example 1.
Comparative example 2
0.24 w/v% of cetirizine hydrochloride, 0.1 w/v% of edetate disodium, 0.55 w/v% of sodium chloride, 0.5 w/v% of hydroxypropyl methylcellulose, 0.001 w/v% of polyhexamethylene biguanide, and sodium hydroxide, wherein the pH value is adjusted to 7.45, and water for injection is added to reach 100% of the volume;
the preparation method is the same as in example 5.
The experimental results of comparative example 1 and comparative example 2 are as follows:
the results show that all indexes of the eye drops prepared in the examples 1, 2, 3 and 4 are qualified, but the eye drops are unqualified in the examination of the bacteriostatic efficacy for 3 months, the cetirizine hydrochloride eye drops prepared in the examples 5, 6, 7 and 8 are qualified in the examination of the pH, the content and the bacteriostatic efficacy, and related substances of the cetirizine hydrochloride eye drops are obviously superior to those of ZERVIATE, so that the eye drops have better long-term stability. The indexes of the eye drops prepared in the comparative examples 1 and 2 are all qualified when the eye drops are zero, but the related substances and the bacteriostatic efficacy of 3 months are not qualified.
The present invention has been described above by way of example, but the present invention is not limited to the above-described specific embodiments, and any modification or variation made based on the present invention is within the scope of the present invention as claimed.
Claims (6)
1. A cetirizine hydrochloride aqueous pharmaceutical composition, which is characterized in that: comprises the following components in parts by weight: 15-18 parts of cetirizine hydrochloride, 50-55 parts of osmotic pressure regulator, 50-55 parts of thickening agent, 8-11 parts of pH regulator and 0.01-0.02 part of preservative; the above components have a pH of 7.0 to 7.8 and an osmolality of 250 to 290 mOsmol/kg.
2. The cetirizine hydrochloride aqueous pharmaceutical composition of claim 1, wherein: the osmotic pressure regulator is sodium chloride.
3. The cetirizine hydrochloride aqueous pharmaceutical composition of claim 1, wherein: the pH regulator is hydrochloric acid and sodium hydroxide.
4. The cetirizine hydrochloride aqueous pharmaceutical composition of claim 1, wherein: the preservative is polyhexamethylene biguanide.
5. The cetirizine hydrochloride aqueous pharmaceutical composition of claim 1, wherein: the thickening agent is hydroxypropyl methylcellulose.
6. The method for preparing a cetirizine hydrochloride aqueous pharmaceutical composition according to claim 1, characterized in that:
(1) firstly, sequentially adding a pH regulator, an osmotic pressure regulator and cetirizine hydrochloride into a proper amount of water, and continuously stirring until the pH regulator, the osmotic pressure regulator and the cetirizine hydrochloride are dissolved;
(2) adding the thickening agent into a proper amount of water, continuously stirring until the thickening agent is uniformly dispersed, and adding the preservative;
(3) mixing the two solutions and then continuously stirring; dropwise adding sodium hydroxide to adjust the pH of the solution to 7.45, and then supplementing enough water for injection;
(4) packaging with lid after subpackaging.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010446780.8A CN113712908A (en) | 2020-05-25 | 2020-05-25 | Composition for treating allergic conjunctivitis and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010446780.8A CN113712908A (en) | 2020-05-25 | 2020-05-25 | Composition for treating allergic conjunctivitis and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN113712908A true CN113712908A (en) | 2021-11-30 |
Family
ID=78671512
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202010446780.8A Pending CN113712908A (en) | 2020-05-25 | 2020-05-25 | Composition for treating allergic conjunctivitis and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN113712908A (en) |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20100240625A1 (en) * | 2009-03-17 | 2010-09-23 | Aciex Therapeutics, Inc. | Ophthalmic Formulations of Cetirizine and Methods of Use |
| CN101959509A (en) * | 2008-03-07 | 2011-01-26 | 金伯利-克拉克环球有限公司 | Alcohol antimicrobial skin sanitizing compositions including cationic compatible thickeners |
| CN102246793A (en) * | 2011-06-08 | 2011-11-23 | 江中药业股份有限公司 | Antimicrobial composition and use thereof |
| CN107875119A (en) * | 2017-11-22 | 2018-04-06 | 山东绅联药业有限公司 | A kind of emedastine difumarate aqueous pharmaceutical compositions and preparation method thereof |
| US20200030320A1 (en) * | 2017-02-13 | 2020-01-30 | Nitto Medic Co., Ltd. | Aqueous composition for eye drops and nasal drops |
-
2020
- 2020-05-25 CN CN202010446780.8A patent/CN113712908A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101959509A (en) * | 2008-03-07 | 2011-01-26 | 金伯利-克拉克环球有限公司 | Alcohol antimicrobial skin sanitizing compositions including cationic compatible thickeners |
| US20100240625A1 (en) * | 2009-03-17 | 2010-09-23 | Aciex Therapeutics, Inc. | Ophthalmic Formulations of Cetirizine and Methods of Use |
| CN102246793A (en) * | 2011-06-08 | 2011-11-23 | 江中药业股份有限公司 | Antimicrobial composition and use thereof |
| US20200030320A1 (en) * | 2017-02-13 | 2020-01-30 | Nitto Medic Co., Ltd. | Aqueous composition for eye drops and nasal drops |
| CN107875119A (en) * | 2017-11-22 | 2018-04-06 | 山东绅联药业有限公司 | A kind of emedastine difumarate aqueous pharmaceutical compositions and preparation method thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP2785328B1 (en) | Novel slow-releasing ophthalmic compositions comprising povidone iodine | |
| JP5394927B2 (en) | Self-preserving aqueous pharmaceutical composition | |
| EP2747772B1 (en) | Ophthalmic formulations | |
| US11376214B2 (en) | Compositions and methods for treatment of ocular diseases | |
| EP1395215B1 (en) | Quinolone carboxylic acid compositions and related methods of treatment | |
| WO2001047521A1 (en) | Use of ketotifen as ophthalmic agent | |
| WO2022012304A1 (en) | Ophthalmic pharmaceutical composition | |
| CN107875119B (en) | Emedastine fumarate aqueous pharmaceutical composition and preparation method thereof | |
| KR20100017168A (en) | N-halogenated amino acid formulations and methods for cleaning and disinfection | |
| CN113712908A (en) | Composition for treating allergic conjunctivitis and preparation method thereof | |
| JP2004315472A (en) | Ophthalmological preparation, eye lotion, artificial tear, contact lens care goods, eyewash and eye ointment | |
| JPWO2002040028A1 (en) | Antibacterial gel eye drops | |
| US20210290527A1 (en) | Compositions and Methods for Treatment of Ocular Conditions | |
| JP2007513951A (en) | Use of organic buffers to enhance the antimicrobial activity of pharmaceutical compositions | |
| AU2010236505B2 (en) | Aqueous ophthalmic compositions containing anionic therapeutic agents | |
| EP2800573B1 (en) | Ophthalmic composition | |
| CA2835013C (en) | Eye drops for treatment of conjunctivochalasis | |
| WO2022101821A1 (en) | Formulation based on polyhexamethylene biguanide for use in the treatment of acanthamoeba keratitis and/or fungal infections | |
| CN114306228A (en) | Diquafosol sodium eye drops and preparation method thereof | |
| CN115595214A (en) | Corneal contact lens nursing composition, preparation method and application thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20211130 |
|
| WD01 | Invention patent application deemed withdrawn after publication |