CN113521003B - Ophthalmic composition and preparation method and application thereof - Google Patents
Ophthalmic composition and preparation method and application thereof Download PDFInfo
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- CN113521003B CN113521003B CN202110257378.XA CN202110257378A CN113521003B CN 113521003 B CN113521003 B CN 113521003B CN 202110257378 A CN202110257378 A CN 202110257378A CN 113521003 B CN113521003 B CN 113521003B
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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
- A61K9/10—Dispersions; Emulsions
- A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
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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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
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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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
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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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
- A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
- A61K47/186—Quaternary ammonium compounds, e.g. benzalkonium chloride or cetrimide
-
- 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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
-
- 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
- A61K47/44—Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
-
- 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
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/04—Artificial tears; Irrigation solutions
Abstract
The invention discloses an ophthalmic composition, a preparation method and application thereof, belongs to ophthalmic solutions, and relates to ophthalmic compositions. An ophthalmic composition comprising 0.001% -0.1% of a cationic agent by total mass of the composition, the cationic agent being cetyldimethylbenzylammonium chloride, 0.1% -1.0% of a first emulsion span by total mass of the composition, 0.1% -0.5% of a second emulsion by total mass of the composition, the second emulsion being octylphenol polyether-40, tyloxapol, or poloxamer 188, 0.1% -5% of an oil phase by total mass of the composition, 0.001% -0.25% of a pH regulator by total mass of the composition, and 0.5% -3% of an osmotic pressure regulator by total mass of the composition. The cationic agent CKC has excellent compatibility with the first and second emulsion compound emulsions, better stability and low eye irritation.
Description
Technical Field
The invention belongs to an ophthalmic solution, relates to an ophthalmic composition, and particularly relates to an ophthalmic composition, and a preparation method and application thereof.
Background
Dry eye disorders are largely divided into two types: firstly, dry eye is lachrymally deficient, i.e. decreased tear secretion and normal evaporation; the second is evaporative dry eye, i.e. the tears are secreted normally and evaporated too much, accounting for over 80% of dry eye people. Improving the quality and quantity of tears, forming a stable tear film, is a positive method for dry eye prevention and relief. The artificial tears are mainly used for treating mild xerophthalmia, and the main product on the market is sodium hyaluronate artificial tears, but the product has the defects of short retention time of tear film, 5-6 drops per day and poor patient compliance.
At present, oil-water emulsion artificial tears on the market are few, and part of reasons are that the emulsion has poor stability, so that the problem of layering demulsification is easily caused, and the defect of poor treatment effect is caused.
In order to solve the above problems of the prior art, the present inventors have developed an ophthalmic composition having better stability and less toxic and side effects.
Disclosure of Invention
The invention aims to provide a composition for forming a stable tear film and improving xerophthalmia, and the composition has the advantages of good stability, good curative effect and no toxic or side effect.
It is another object of the present invention to provide a process for the preparation of the above ophthalmic composition.
It is a further object of the present invention to provide the use of the above ophthalmic compositions.
The invention is realized by the following technical scheme:
an ophthalmic composition comprising:
0.001-0.1% of cationic agent cetyl dimethyl benzyl ammonium chloride (CKC) of the total mass of the composition,
0.1-1.0% of the total mass of the composition of a first emulsion span,
a second emulsion accounting for 0.1-0.8% of the total mass of the composition, wherein the second emulsion is octyl phenol polyether-40 (Octoxynol 40), Tyloxapol (Tyloxapol), or Poloxamer 188 (Poloxamer 188),
An oil phase accounting for 0.5 to 3 percent of the total mass of the composition,
0.001-0.25% of pH regulator based on the total weight of the composition,
an osmotic pressure regulator accounting for 0.5-3% of the total mass of the composition.
Further, the HLB value of the composition is 9.5-10.5.
The first emulsion is span-20, span-40, span-60, span-65, span-80 or span-85, wherein span-20 is preferred.
The oil phase comprises light mineral oil, and/or heavy mineral oil, and/or medium chain triglyceride.
The pH regulator is tromethamine.
The osmotic pressure regulator is glycerol, propylene glycol, sorbitol and/or mannitol.
The preparation method of the ophthalmic composition comprises the following steps: respectively heating the oil phase and the water phase of the emulsion to 70-85 deg.C, slowly pouring the oil phase into the water phase under rapid mechanical stirring, continuously stirring for 8-20 min, homogenizing and mixing for at least 30 min under high shear to reduce oil droplets as much as possible, and adding pH regulator to make the average particle size of colloid particles of the emulsion equal to or less than 100 nm.
The invention also discloses application of the ophthalmic composition as a medicine carrier in preparation of a medicine for xerophthalmia.
The invention also discloses application of the ophthalmic composition in preparing artificial tears.
The cationic agent in the composition uses hexadecyl dimethyl benzyl ammonium chloride, the number of the emulsion is two, the first emulsion is Span, the second emulsion selects Octoxynol 40 or Tyloxapol or Poloxamer 188, wherein Span and the cationic agent CKC are compounded to form a compact interfacial film, and the second emulsion can increase the acting force between the Span and the nonionic surfactant and enhance the emulsification effect, so that the emulsion system has good compatibility and the emulsion has stronger stability; by calculating HLB value (HLB = HLB)A*A%+ HLBBB%, wherein a% and B% represent the mass percentage of the two emulsions), stabilizing it at about 9.5-10.5, preferably 10,that is, the HLB value required for emulsification of the oil phase is matched, so that the composition forms a stable interfacial film to achieve the best emulsification effect. The eye composition combines the CKC, the span and the second emulsion, so that the eye composition achieves stable and uniform effect, is used as a medicine carrier or artificial tears, increases the stability of the tear film, protects the corneal epithelium, and has the advantages of good curative effect, quick response and no toxic or side effect.
Compared with the prior art, the invention has the following advantages:
(1) the cationic agent CKC has excellent compatibility with the first and second emulsion compound emulsion, and has better stability;
(2) No preservative is used, so that the eye irritation is reduced, and the compliance of patients is improved;
(3) can improve the solubility of ophthalmic medicine suitable for the system, and can be used as a carrier of ophthalmic medicine.
Detailed Description
Example 1
Compositions were prepared according to the components shown in table 1 to obtain three compositions of group 1, group 2, and group 3, respectively.
TABLE 1
| Components | Group 1 percent | Group 2 percent | Group 3 percent |
| Light mineral oil | 0.50% | 1.0% | 0.1% |
| Heavy mineral oil | 0.50% | 1.0% | 0 |
| Medium chain triglycerides | 0 | 0.50% | 0 |
| CKC | 0.002% | 0.05% | 0.08% |
| Span 20 | 0.30% | 0.64% | 0.90% |
| Octoxynol 40 | 0.10% | 0 | 0 |
| Tyloxapol | 0 | 0.36% | 0 |
| Poloxamer 188 | 0 | 0 | 0.10% |
| Tromethamine | 0.071% | 0.005% | 0.25% |
| Glycerol | 2.50% | 1% | 1.50% |
| Water (W) | Balance of | Balance of | Balance of |
The preparation method comprises the following steps:
1) dissolving span 20 and a second emulsion Octoxynol 40, Tyloxapol, or Poloxamer 188 in the oil phase;
2) dissolving CKC, an osmotic pressure regulator glycerol and tromethamine in an aqueous phase;
3) respectively heating the water phase and the oil phase to a proper temperature of 70-85 ℃, slowly pouring the oil phase into the water phase under the condition of rapid mechanical stirring, continuously stirring for 10 minutes, supplementing water for injection to the full amount, carrying out high-shear homogeneous mixing for at least 30 minutes to reduce oil drops as much as possible, and adjusting the pH value to 6.2 by using dilute hydrochloric acid.
Span 20 can be replaced by span-40, span-60, span-65, span-80 or span-85, it should be noted that since the HLB value of different types of spans is different, the HLB value of the mixture of the two emulsions should be calculated to stabilize it at 10, which matches the HLB value required for emulsification of the oil phase.
When a drug for dry eye is produced, the composition obtained by the above method is used as a drug carrier, an effective amount of a drug such as cyclosporin is added to the composition, and eye drops are prepared under autoclaving conditions.
When preparing an artificial tear, the composition obtained as described above is loaded into a suitable container and sterilized by autoclaving to prepare an artificial tear eye drop.
Example 2
Compositions were prepared according to the components shown in Table 2 to obtain three compositions of comparative group 1, comparative group 2 and comparative group 3, respectively.
TABLE 2
| Components | Comparative 1 percent | Comparative 2 percent | Comparative 3 percent |
| Light mineral oil | 0.50% | 1.0% | 0.1% |
| Heavy mineral oil | 0.50% | 1.0% | 0 |
| Medium chain triglycerides | 0 | 0.5% | 0 |
| CKC | 0.002% | 0.05% | 0.08% |
| Span 20 | 0 | 0.10% | 0 |
| Octoxynol 40 | 0 | 0 | 0.50% |
| Tyloxapol | 0.27% | 0 | 0 |
| Poloxamer 188 | 0.13% | 0 | 0 |
| Tromethamine | 0.071% | 0.005% | 0.25% |
| Glycerol | 2.50% | 1.0% | 3.0% |
| Water (W) | Balance of | Balance of | Balance of |
The above 6 compositions were subjected to a 3 month accelerated stability test and a rabbit eye Draize eye irritation test according to pharmacopoeia specifications, and the test data are shown in table 3:
TABLE 3
| Observation for 0 day | 3 month appearance | Irritation score | |
| Group 1 | Homogeneous emulsion | Homogeneous emulsion | 1.55 |
| Group 2 | Homogeneous emulsion | Homogeneous emulsion | 1.72 |
| Group 3 | Homogeneous emulsion | Homogeneous emulsion | 1.60 |
| Comparative group 1 | Homogeneous emulsion | Apparent delamination | 2.41 |
| Comparative group 2 | Homogeneous emulsion | Apparent delamination | 2.30 |
| Comparative group 3 | Homogeneous emulsions | Apparent delamination | 2.32 |
As can be seen from Table 3, the ionic agent CKC has excellent compatibility with the first and second emulsion compound emulsions, better long-term storage stability and lower eye irritation.
Example 3
Compositions were prepared according to the components shown in table 4 to obtain five compositions of group 4, group 5, group 6, group 7, and group 8, respectively.
TABLE 4
| Components | Group 4 percent | Group 5 percent | Group 6 percent | Group 7 percent | Group 8 percent |
| Light mineral oil | 0.50% | 2.0% | 1.0% | 1.0% | 0 |
| Heavy mineral oil | 0.50% | 1.0% | 1.0% | 1.0% | 0 |
| Medium chain triglycerides | 0 | 0 | 0 | 0 | 0.5% |
| CKC | 0.001% | 0.1% | 0.01% | 0.09% | 0.05% |
| Span 40 | 0.85% | 0 | 0 | 0 | 0 |
| Span 60 | 0 | 1.0% | 0 | 0 | 0 |
| Span 65 | 0 | 0 | 0.25% | 0 | 0 |
| Span 80 | 0 | 0 | 0 | 0.87% | |
| Span 85 | 0 | 0 | 0 | 0 | 0.10% |
| Octoxynol 40 | 0 | 0.67% | 0 | 0.63% | 0 |
| Tyloxapol | 0 | 0 | 0.80% | 0 | 0.40% |
| Poloxamer 188 | 0.15% | 0 | 0 | 0 | 0 |
| Tromethamine | 0.001% | 0.10% | 0.25% | 0.25% | 0.25% |
| Glycerol | 3.0% | 1.0% | 1.50% | 0.50% | 1.50% |
| Water (W) | Balance of | Balance of | Balance of | Balance of | Balance of |
The preparation method comprises the following steps:
1) dissolving span 40 or span 60 or span 65 or span 80 or span 85 and second emulsion Octoxynol 40 or Tyloxapol or Poloxamer 188 in the oil phase;
2) dissolving CKC, an osmotic pressure regulator glycerol and tromethamine in an aqueous phase;
3) heating the water phase and the oil phase to appropriate temperature of 70-85 deg.C respectively, slowly pouring the oil phase into the water phase under rapid mechanical stirring, continuously stirring for 10 min, adding water for injection to full volume, homogenizing and mixing for at least 30 min under high shear to reduce oil droplets as much as possible, and adjusting pH to 6.2 with dilute hydrochloric acid to obtain HLB value of 9.5-10.5.
The above 5 compositions were subjected to a stability test under an accelerated condition for 3 months according to pharmacopoeia regulations, and the measured experimental data are shown in table 5:
TABLE 5
| Observation for 0 day | 3 month appearance | |
| Group 4 | Homogeneous emulsion | Homogeneous emulsion |
| Group 5 | Homogeneous emulsion | Homogeneous emulsion |
| Group 6 | Homogeneous emulsion | Homogeneous emulsion |
| Group 7 | Homogeneous emulsion | Homogeneous emulsion |
| Group 8 | UniformityEmulsion and method of making | Homogeneous emulsion |
The compositions in tables 1 and 4 above can also be used as eye drop drug carriers as usual.
The above description is only for the preferred embodiment of the present invention, but the scope of the present invention is not limited thereto, and any person skilled in the art should be able to cover the technical scope of the present invention and the equivalent alternatives or modifications according to the technical solution and the inventive concept of the present invention within the technical scope of the present invention.
Claims (10)
1. An ophthalmic composition, comprising:
0.001 to 0.1 percent of cationic agent cetyl dimethyl benzyl ammonium chloride based on the total mass of the composition,
0.1 to 1.0 percent of the total mass of the composition of a first emulsifier span,
a second emulsifier accounting for 0.1-0.8% of the total mass of the composition, wherein the second emulsifier is octyl phenol polyether-40, tyloxapol or poloxamer 188,
An oil phase accounting for 0.5 to 3 percent of the total mass of the composition,
0.001-0.25% of pH regulator based on the total weight of the composition,
an osmotic pressure regulator accounting for 0.5 to 3 percent of the total mass of the composition,
the balance being water.
2. An ophthalmic composition as in claim 1, comprising: the HLB value of the composition is 9.5-10.5.
3. An ophthalmic composition according to claim 1 or 2, characterized in that the first emulsifier is span-20, span-40, span-60, span-65, span-80, or span-85.
4. An ophthalmic composition according to claim 1 or 2, wherein the first emulsifier is span 20.
5. An ophthalmic composition according to claim 1, wherein the oily phase comprises light mineral oil, and/or heavy mineral oil, and/or medium chain triglycerides.
6. An ophthalmic composition according to claim 1 or 2, wherein the pH adjusting agent is tromethamine.
7. An ophthalmic composition according to claim 1 or 2, wherein the tonicity modifier is glycerol, propylene glycol, sorbitol and or mannitol.
8. A process for the preparation of the ophthalmic composition according to any one of claims 1 to 7, comprising the steps of: respectively heating the oil phase and the water phase of the emulsion to 70-85 deg.C, slowly pouring the oil phase into the water phase under rapid mechanical stirring, continuously stirring for 8-20 min, homogenizing and mixing for at least 30 min under high shear to reduce oil droplets as much as possible, and adding pH regulator to make the average particle size of colloid particles of the emulsion equal to or less than 100 nm.
9. Use of the ophthalmic composition of any one of claims 1 to 7 as a pharmaceutical carrier in the manufacture of a medicament for dry eye.
10. Use of the ophthalmic composition according to any one of claims 1 to 7 for the preparation of artificial tears.
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| CN114588110B (en) * | 2022-03-25 | 2023-08-04 | 山西利普达医药科技有限公司 | Ophthalmic drug emulsion composition and preparation method and application thereof |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1879605A (en) * | 2005-06-17 | 2006-12-20 | 中国科学院上海药物研究所 | A micro-emulsion type artificial tear |
| CN101028240A (en) * | 2007-03-29 | 2007-09-05 | 中国科学院上海药物研究所 | Micro-emulsion/submicro-emulsion in-situ gel preparation for eyes and its making method |
| CN101653413A (en) * | 2009-09-25 | 2010-02-24 | 宋洪涛 | Tacrolimus ophthalmic emulsion and its preparation method |
| CN102223876A (en) * | 2008-09-26 | 2011-10-19 | 纳米生物公司 | Nanoemulsion therapeutic compositions and methods of using the same |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9144606B2 (en) * | 2008-04-21 | 2015-09-29 | Nanobio Corporation | Nanoemulsion influenza vaccine |
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1879605A (en) * | 2005-06-17 | 2006-12-20 | 中国科学院上海药物研究所 | A micro-emulsion type artificial tear |
| CN101028240A (en) * | 2007-03-29 | 2007-09-05 | 中国科学院上海药物研究所 | Micro-emulsion/submicro-emulsion in-situ gel preparation for eyes and its making method |
| CN102223876A (en) * | 2008-09-26 | 2011-10-19 | 纳米生物公司 | Nanoemulsion therapeutic compositions and methods of using the same |
| CN101653413A (en) * | 2009-09-25 | 2010-02-24 | 宋洪涛 | Tacrolimus ophthalmic emulsion and its preparation method |
Non-Patent Citations (4)
| Title |
|---|
| A novel eye drop of alpha tocopherol to prevent ocular oxidant damage: improve the stability and ocular efficacy;Xin Jiayu等;《Drug Development and Industrial Pharmacy》;20161231;第42卷(第2期);第525-534页 * |
| Development of loteprednol etabonate-loaded cationic nanoemulsified in-situ ophthalmic gel for sustained delivery and enhanced ocular bioavailability;Patel Nirav等;《Drug Delivery》;20161231;第23卷(第9期);第3712-3723页 * |
| 眼用微粒给药系统的研究进展;甘勇，等;《中国药学杂志》;20060731;第41卷(第13期);第967-970页 * |
| 眼部剂型研究进展;李骄，等;《中国中医眼科杂志》;20131031;第23卷(第5期);第381-383页 * |
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