CN105997856A - Oxymetazoline hydrochloride eye drops and preparing method thereof - Google Patents
Oxymetazoline hydrochloride eye drops and preparing method thereof Download PDFInfo
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- CN105997856A CN105997856A CN201610473276.0A CN201610473276A CN105997856A CN 105997856 A CN105997856 A CN 105997856A CN 201610473276 A CN201610473276 A CN 201610473276A CN 105997856 A CN105997856 A CN 105997856A
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- oxymetazoline hydrochloride
- acid
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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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4174—Arylalkylimidazoles, e.g. oxymetazolin, naphazoline, miconazole
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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
-
- 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
-
- 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
- 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
- A61K47/46—Ingredients of undetermined constitution or reaction products thereof, e.g. skin, bone, milk, cotton fibre, eggshell, oxgall or plant extracts
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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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/08—Solutions
Abstract
The invention discloses oxymetazoline hydrochloride eye drops and a preparing method thereof. The oxymetazoline hydrochloride eye drops are light in irritation to eyes, comfortable in use, stable in quality and more durable in efficacy.
Description
Technical field
The present invention relates to technical field of medicine, concrete, the present invention relates to oxymetazoline hydrochloride eye drop and preparation side thereof
Method.
Background technology
Oxymetazoline hydrochloride is the sympathomimetic drug with vasoconstrictive effect, and its effect is directly to stimulate vascular smooth muscle
On α 1 receptor.Oxymetazoline hydrochloride eye drop is used clinically for alleviating anaphylaxis conjunctivitis, non-infectious conjunctivitis
Eye symptom and release allergy, eye that xerophthalmia, swimming, smog, the factor such as contact lens, eyestrain of wearing cause congested.
The oxymetazoline hydrochloride eye drop specification listed is 5ml:1.25mg and 10ml:2.5mg.Usage and dosage is: instill in eyelid,
One time 1～2,2～4 times on the one.
But, current oxymetazoline hydrochloride eye drop and preparation method thereof still haves much room for improvement.
Summary of the invention
It is contemplated that one of technical problem solved the most to a certain extent in correlation technique.To this end, the one of the present invention
Purpose be to propose a kind of little to Ocular irritation, use hydrochloric acid hydroxyl first comfortable, that drug quality is stable, curative effect is more lasting
Oxazoline eye drop.
In one aspect of the invention, the invention provides a kind of oxymetazoline hydrochloride eye drop.According to embodiments of the invention,
This oxymetazoline hydrochloride eye drop includes: oxymetazoline hydrochloride；And pharmaceutically acceptable adjuvant.Inventor finds, this
The oxymetazoline hydrochloride eye drop of invention is little to Ocular irritation, side effect is little, it is comfortable to use, drug quality is stable, it is possible to
Maintain medicine effective concentration time length, curative effect more lasting, and preparation technology is simple, low cost, is suitable for industrialized production.
According to embodiments of the invention, described pharmaceutically acceptable adjuvant is selected from osmotic pressure regulator, thickening agent, refrigerant
At least one of agent, antibacterial, acid-base modifier and ethanol.
According to embodiments of the invention, described osmotic pressure regulator is selected from sodium chloride, potassium chloride, disodium hydrogen phosphate, phosphoric acid
At least one in sodium dihydrogen, boric acid, Borax, glycerol, glucose, the consumption of described osmotic pressure regulator is with reference to ophthalmology system
Agent standard.According to a particular embodiment of the invention, the most described osmotic pressure regulator is selected from sodium chloride.Thereby, it is possible to change
Kind medicine, to Ocular irritation, the comfortableness of raising drug use further, improves the quality stability of medicine, obtains curative effect
More lasting oxymetazoline hydrochloride eye drop.
According to embodiments of the invention, described thickening agent is selected from polyvinyl alcohol, hypromellose, hyaluronic acid sodium, poly-dimension
At least one in ketone, Polyethylene Glycol.According to a particular embodiment of the invention, the most described thickening agent be selected from polyvinyl alcohol,
At least one in hypromellose, Polyethylene Glycol.Thereby, it is possible to improve medicine to Ocular irritation, improve further
The comfortableness of drug use, improves the quality stability of medicine, obtains the oxymetazoline hydrochloride eye drop that curative effect is more lasting.
According to embodiments of the invention, described freshener be selected from Herba Menthae, Borneolum Syntheticum at least one.Concrete according to the present invention
Embodiment, the most described freshener is the combination selected from Borneolum Syntheticum and Herba Menthae.Thereby, it is possible to improve medicine to Ocular irritation,
Improve the comfortableness of drug use further, improve the quality stability of medicine, obtain the hydrochloric acid hydroxymethyl thiazole that curative effect is more lasting
Quinoline eye drop.
According to embodiments of the invention, described antibacterial is selected from Benasept, ethyl hydroxybenzoate, ethyl hydroxybenzoate, trichlorine uncle
At least one in butanol, benzalkonium chloride, benzalkonium bromide, sorbic acid, benzoic acid.According to a particular embodiment of the invention,
Described antibacterial is at least one in benzalkonium bromide, sorbic acid.Thereby, it is possible to improve medicine to Ocular irritation,
Improve the comfortableness of drug use further, improve the quality stability of medicine, obtain the hydrochloric acid hydroxymethyl thiazole that curative effect is more lasting
Quinoline eye drop.
According to embodiments of the invention, described acid-base modifier be selected from hydrochloric acid, boric acid, citric acid, sodium hydroxide, Borax,
At least one in sodium citrate.According to a particular embodiment of the invention, described acid-base modifier is selected from sodium hydroxide.By
This, it is possible to improve medicine to Ocular irritation, the comfortableness that improves further drug use, improve medicine quality stability,
Obtain the oxymetazoline hydrochloride eye drop that curative effect is more lasting.
According to embodiments of the invention, according to parts by weight, the prescription composition of described oxymetazoline hydrochloride eye drop may include that
Described oxymetazoline hydrochloride 2.5 weight portion, described osmotic pressure regulator 90 weight portion, described thickening agent 10-100 weight portion,
Described freshener 1-2 weight portion, described antibacterial 0.5-1 weight portion, described acid-base modifier is appropriate, described appropriate amount of ethanol.
Thereby, it is possible to improve medicine to Ocular irritation, the comfortableness of raising drug use further, the steady quality of raising medicine
Property, obtain the oxymetazoline hydrochloride eye drop that curative effect is more lasting.
Inventor tests through substantial amounts of eye comfortableness and Ocular irritation and finds, when thickening agent of the present invention is hydroxypropyl first
At least one and freshener of cellulose and Polyethylene Glycol is selected from Borneolum Syntheticum and when being applied in combination of Herba Menthae, hydrochloric acid of the present invention
Oxymetazoline eye drop is minimum to the zest of eyes, use the most comfortable.Further, more preferably Borneolum Syntheticum and Herba Menthae is by quality
Combination matching than 3: 1 uses, and effect is best.
In another aspect of this invention, the invention provides the method preparing foregoing oxymetazoline hydrochloride eye drop.Root
According to embodiments of the invention, the method comprises the following steps: (1) by described oxymetazoline hydrochloride, osmotic pressure regulator, press down
Microbial inoculum mixes, and joins water for injection to the mixture obtained, and after stirring to dissolving, heats up and boils 15-30min, be cooled to
Room temperature, obtains the first solution；(2) freshener is dissolved in ethanol in proper amount, stirs, obtain the second solution；(3)
Described first solution and described first solution are mixed, obtains the 3rd solution；(4) in described 3rd solution, increasing is added
Stick, stirs, and utilizes acid-base modifier to adjust pH value to be 4.0-5.0, and constant volume obtains the 4th solution；(5) use
Described 4th solution is filtered by the microporous membrane of 0.45um, in order to obtain described oxymetazoline hydrochloride eye drop.Wherein, step
Suddenly, in (1), the amount of the water for injection of use can be the 2/3 of preparation cumulative volume.
According to embodiments of the invention, after present invention application viscosifier and freshener, preparation-obtained oxymetazoline hydrochloride drips
Ocular fluid is high to eye comfort level.According to embodiments of the invention, the oxymetazoline hydrochloride eye drop prepared of the present invention,
Its side effect is little, and comfort level and the zest to eye are superior to existing commercially available oxymetazoline hydrochloride eye drop.
According to the commercially available prod situation that pH value declines during storing, we are mainly for the pH value of this eye drop, by this
Bright described oxymetazoline hydrochloride eye drop carries out study on the stability, and the investigation condition of stability study is: heat: 40 DEG C；Light:
4500lux, and carried out accelerating 2 months, accelerating 3 months and the room temperature detection data of 3 months.Result shows: this
The prescription of invention is more stable, and pH value is not changed in substantially, constant product quality.Apply polyvinyl alcohol of the present invention, hydroxyl
Third methylcellulose, Polyethylene Glycol are as the viscosifier of oxymetazoline hydrochloride eye drop of the present invention, and the pH value of this product is steady
Fixed, constant product quality.And, application viscosifier after, make oxymetazoline hydrochloride eye drop at eye increased retention,
It is able to maintain that medicine effective concentration time length, curative effect are more lasting.And oxymetazoline hydrochloride eye drop system of the present invention
Standby technique is simple, low cost, is suitable for industrialized production.
Detailed description of the invention
Embodiments of the invention are described below in detail.The embodiments described below is exemplary, is only used for explaining the present invention,
And be not considered as limiting the invention.
The prescription screening of embodiment 1 oxymetazoline hydrochloride eye drop and preparation
Prescription one～prescription eight:
Table 1
Wherein, the preparation method of prescription one:
(1) by described oxymetazoline hydrochloride, sodium chloride, benzalkonium bromide mixing, the note about preparing cumulative volume 2/3 is joined
Penetrate with in water, stir the most molten after, 30min is boiled in intensification, is cooled to room temperature, obtains solution, standby；(2) by described Borneolum Syntheticum
It is dissolved in ethanol in proper amount with Herba Menthae, stirs, add to step (1) described solution；(3) polyvinyl alcohol is added
To step (1) described solution, stirring, the sodium hydroxide solution of 0.1M adjusts pH value 4.5, constant volume；(4) check
The micro-pore-film filtration of qualified rear 0.45um is to clear and bright, and subpackage prepares oxymetazoline hydrochloride eye drop.
The preparation method of prescription two:
(1) by described oxymetazoline hydrochloride, sodium chloride, sorbic acid mixing, the injection about preparing cumulative volume 2/3 is joined
With in water, stir the most molten after, heat up and boil 30min, be cooled to room temperature, obtain solution, standby；(2) by described Borneolum Syntheticum and
Herba Menthae is dissolved in ethanol in proper amount, stirs, and adds to step (1) described solution；(3) hypromellose is added
Entering to step (1) described solution, stir, the sodium hydroxide solution of 0.1M adjusts pH value 4.5, constant volume；(4) inspection
The micro-pore-film filtration looking into qualified rear 0.45um is the most clear and bright, and subpackage prepares oxymetazoline hydrochloride eye drop.
The preparation method of prescription three:
(1) by described oxymetazoline hydrochloride, sodium chloride, benzalkonium bromide mixing, the note about preparing cumulative volume 2/3 is joined
Penetrate with in water, stir the most molten after, 30min is boiled in intensification, is cooled to room temperature, obtains solution, standby；(2) by described Borneolum Syntheticum
It is dissolved in ethanol in proper amount with Herba Menthae, stirs, add to step (1) described solution；(3) hyaluronic acid sodium is added
To step (1) described solution, stirring, the sodium hydroxide solution of 0.1M adjusts pH value 4.5, constant volume；(4) check
The micro-pore-film filtration of qualified rear 0.45um is to clear and bright, and subpackage prepares oxymetazoline hydrochloride eye drop.
The preparation method of prescription four:
(1) by described oxymetazoline hydrochloride, sodium chloride, sorbic acid mixing, the injection about preparing cumulative volume 2/3 is joined
With in water, stir the most molten after, heat up and boil 30min, be cooled to room temperature, obtain solution, standby；(2) by described Borneolum Syntheticum and
Herba Menthae is dissolved in ethanol in proper amount, stirs, and adds to step (1) described solution；(3) polyvidone is added to step
Suddenly in (1) described solution, stirring, the sodium hydroxide solution of 0.1M adjusts pH value 4.5, constant volume；(4) passed examination
Afterwards with the micro-pore-film filtration of 0.45um to clear and bright, subpackage prepares oxymetazoline hydrochloride eye drop.
The preparation method of prescription five:
(1) by described oxymetazoline hydrochloride, sodium chloride, benzalkonium bromide mixing, the note about preparing cumulative volume 2/3 is joined
Penetrate with in water, stir the most molten after, 30min is boiled in intensification, is cooled to room temperature, obtains solution, standby；(2) by described Borneolum Syntheticum
It is dissolved in ethanol in proper amount with Herba Menthae, stirs, add to step (1) described solution；(3) Polyethylene Glycol is added
To step (1) described solution, stirring, the sodium hydroxide solution of 0.1M adjusts pH value 4.5, constant volume；(4) check
The micro-pore-film filtration of qualified rear 0.45um is to clear and bright, and subpackage prepares oxymetazoline hydrochloride eye drop.
The preparation method of prescription six is with prescription five.
Prescription seven is to be added without viscosifier and freshener in comparative example 1, specially prescription only with Borneolum Syntheticum, its system
Method is:
(1) by described oxymetazoline hydrochloride, sodium chloride, benzalkonium bromide mixing, the note about preparing cumulative volume 2/3 is joined
Penetrate with in water, stir the most molten after, 30min is boiled in intensification, is cooled to room temperature, obtains solution, standby；(2) by described Borneolum Syntheticum
It is dissolved in ethanol in proper amount, stirs, add to step (1) described solution；Stir, the hydroxide of 0.1M
Sodium solution adjusts pH value 4.5, constant volume；(3) the most clear and bright with the micro-pore-film filtration of 0.45um after passed examination, subpackage prepares salt
Acid oxymetazoline eye drop.
Prescription eight is to be added without freshener in comparative example 2, specially prescription, and its preparation method is:
(1) by described oxymetazoline hydrochloride, sodium chloride, benzalkonium bromide mixing, the note about preparing cumulative volume 2/3 is joined
Penetrate with in water, stir the most molten after, 30min is boiled in intensification, is cooled to room temperature, obtains solution, standby；(2) by Polyethylene Glycol
Adding to step (1) described solution, stir, the sodium hydroxide solution of 0.1M adjusts pH value 4.5, constant volume；(3)
With the micro-pore-film filtration of 0.45um to clear and bright after passed examination, subpackage prepares oxymetazoline hydrochloride eye drop.
The eye comfort level of embodiment 2 oxymetazoline hydrochloride eye drop and irritant experiment
This comfort level, irritant experiment have 160 volunteers and participate in, 8 prescriptions described in the total above-described embodiment of experiment,
Each prescription has 20 volunteer personnel at random.In the experiment of this product, in order to increase the comprehensive of result of the test, it is considered to
To age, right and left eyes and the eye health individual variation such as whether, by the intensity of excitement, persistent period, tolerance energy during eye dripping
Power is refined.The statistics of result for convenience, by ascending for the intensity of excitement, the persistent period from short to long, will
Comfort level is divided into 5 grades, respectively 0 ,+, ++, +++, ++++.Concrete condition such as table 2:
Table 2
Can be seen that from above-mentioned table 2, after present invention application viscosifier and freshener, preparation-obtained oxymetazoline hydrochloride eye drip
Liquid is high to eye comfort level.
On the basis of the above, the present inventor continues to choose prescription one, prescription two and prescription five these three comfort level
High prescription and commercially available product, expand experimenter's scope, carry out irritant experiment.The number participating in irritant experiment has 120 people,
Prescription one, prescription two, prescription five and commercially available each 30 people of oxymetazoline hydrochloride eye drop group.Zest is divided into by experiment
Three Estate, i.e. " without, little, big ".Concrete condition such as table 3:
Table 3
Can be seen that from table 2, table 3, the hydrochloric acid hydroxymethyl thiazole that prescription one of the present invention, prescription two, prescription five prepare
Quinoline eye drop, its side effect is little, and comfort level and the zest to eye are superior to existing commercially available oxymetazoline hydrochloride and drip
Ocular fluid.
The study on the stability of embodiment 3 oxymetazoline hydrochloride eye drop
According to the commercially available prod situation that pH value declines during storing, we are mainly for the pH value of this eye drop, by this
Bright described oxymetazoline hydrochloride eye drop carries out study on the stability, and the investigation condition of stability study is: heat: 40 DEG C；Light:
4500lux, and carried out accelerating 2 months, accelerating 3 months and the room temperature detection data of 3 months, it is shown in Table 4.
Table 4
As seen from Table 4, the prescription one of the invention described above, prescription two, prescription five these three prescription, after investigating, pH
Value is not changed in substantially, therefore these three prescription is stable.Accelerated 2 months, acceleration 3 months and 3 months data of room temperature
Showing, the pH of three prescriptions is almost without changing.But apply viscosifier glass respectively described in prescription three and prescription four
After acid sodium, polyvidone, ratio prescription one that pH value all declines, prescription two, prescription five notable.Therefore, of the present invention
Polyvinyl alcohol, hypromellose, Polyethylene Glycol are as the viscosifier of oxymetazoline hydrochloride eye drop of the present invention, this product
The pH stable of product, constant product quality.
Borneolum Syntheticum and the proportioning screening experiment of Herba Menthae in embodiment 4 oxymetazoline hydrochloride eye drop
This experiment is by screening with irritant experiment the eye comfort level of experimenter.
The preparation method of prescription nine～prescription 12 is with prescription five.
It is with the difference of prescription five: in prescription nine, Borneolum Syntheticum is 1:2 with the quality proportioning of Herba Menthae；In prescription ten, Borneolum Syntheticum is with thin
The quality proportioning of lotus is 1:1；In prescription 11, Borneolum Syntheticum is 2:1 with the quality proportioning of Herba Menthae；Borneolum Syntheticum and Herba Menthae in prescription 12
Quality proportioning is 4:1.
This comfort level, irritant experiment have 100 volunteers and participate in, 5 prescriptions described in the total above-described embodiment of experiment,
Each prescription has 20 volunteer personnel at random.In the experiment of this product, in order to increase the comprehensive of result of the test, it is considered to
To age, right and left eyes and the eye health individual variation such as whether, by the intensity of excitement, persistent period, tolerance energy during eye dripping
Power is refined.The statistics of result for convenience, by ascending for the intensity of excitement, the persistent period from short to long, will
Comfort level is divided into 5 grades, respectively 0 ,+, ++, +++, ++++.Concrete condition such as table 5:
Table 5
Can be seen that from above-mentioned table 5, after the Borneolum Syntheticum of present invention application different proportion freshener and the combination of Herba Menthae, prepared by obtain
The oxymetazoline hydrochloride eye drop of prescription five high to eye comfort level, in this prescription five, Borneolum Syntheticum with the quality proportioning of Herba Menthae is
3:1。
On the basis of the above, the present inventor continues to choose at prescription five, prescription 11 and prescription 12 these three
Side's group, expands experimenter's scope, carries out irritant experiment.The number participating in irritant experiment has 90 people, often organizes each 30 people.
Zest is divided into Three Estate by experiment, i.e. " without, little, big ".Concrete condition such as table 6:
Table 6
Can be seen that from table 5, table 6, the oxymetazoline hydrochloride eye drop prepared of the present invention, preferably Borneolum Syntheticum and Herba Menthae
Quality proportioning be 3:1.Now its comfort level and best to the zest of eye.
The preparation of embodiment 5 oxymetazoline hydrochloride eye drop
Prescription 13:
| Oxymetazoline hydrochloride | 2.5g |
| Sodium chloride | 90g |
| Polyvinyl alcohol | 20g |
| Borneolum Syntheticum | 0.75g |
| Herba Menthae | 0.25g |
| Dehydrated alcohol | In right amount |
| Benzalkonium bromide | 0.5g |
| Water for injection adds to | 10000ml |
| Make | 1000 |
Preparation method is with prescription one, wherein, with the sodium hydroxide solution regulation PH4.0 of 0.1M before constant volume.
The preparation of embodiment 6 oxymetazoline hydrochloride eye drop
Prescription 14:
| Oxymetazoline hydrochloride | 2.5g |
| Sodium chloride | 90g |
| Polyvinyl alcohol | 100g |
| Borneolum Syntheticum | 1.5g |
| Herba Menthae | 0.5g |
| Dehydrated alcohol | In right amount |
| Benzalkonium bromide | 1g |
| Water for injection adds to | 10000ml |
| Make | 1000 |
Preparation method is with prescription one, wherein, with the sodium hydroxide solution regulation PH5.0 of 0.1M before constant volume.
The preparation of embodiment 7 oxymetazoline hydrochloride eye drop
Prescription 15:
| Oxymetazoline hydrochloride | 2.5g |
| Sodium chloride | 90g |
| Hypromellose | 60g |
| Borneolum Syntheticum | 0.9g |
| Herba Menthae | 0.3g |
| Dehydrated alcohol | In right amount |
| Sorbic acid | 0.75g |
| Water for injection adds to | 10000ml |
| Make | 1000 |
Preparation method is with prescription two, wherein, with the sodium hydroxide solution regulation PH4.5 of 0.1M before constant volume.
The preparation of embodiment 8 oxymetazoline hydrochloride eye drop
Prescription 16:
| Name of material | Prescription five |
| Oxymetazoline hydrochloride | 2.5g |
| Sodium chloride | 90g |
| Polyethylene Glycol | 10g |
| Borneolum Syntheticum | 0.75g |
| Herba Menthae | 0.25g |
| Dehydrated alcohol | In right amount |
| Benzalkonium bromide | 0.5g |
| Sodium hydroxide | In right amount |
| Water for injection adds to | 10000ml |
| Make | 1000 |
Preparation method is with prescription five, wherein, with the sodium hydroxide solution regulation PH4.0 of 0.1M before constant volume.
The preparation of embodiment 9 oxymetazoline hydrochloride eye drop
Prescription 17:
Preparation method is with prescription five, wherein, with the sodium hydroxide solution regulation PH5.0 of 0.1M before constant volume.
The present inventor utilizes the study on the stability method described in the embodiment of the present invention 3, for the pH value of this eye drop,
Carrying out study on the stability, the investigation condition of stability study is: heat: 40 DEG C；Light: 4500lux.Result shows: the present invention
Prescription 13～prescription 17, through investigation after, prescription is stable, and pH value is not changed in substantially, constant product quality.
In the description of this specification, reference term " embodiment ", " some embodiments ", " example ", " specifically show
Example " or the description of " some examples " etc. means to combine this embodiment or example describes specific features, structure, material or
Feature is contained at least one embodiment or the example of the present invention.In this manual, the schematic representation to above-mentioned term
Necessarily it is directed to identical embodiment or example.And, the specific features of description, structure, material or feature are permissible
One or more embodiment in office or example combine in an appropriate manner.Additionally, in the case of the most conflicting, ability
The feature of the different embodiments described in this specification or example and different embodiment or example can be entered by the technical staff in territory
Row combines and combination.
Although above it has been shown and described that embodiments of the invention, it is to be understood that above-described embodiment is exemplary,
Being not considered as limiting the invention, those of ordinary skill in the art within the scope of the invention can be to above-described embodiment
It is changed, revises, replaces and modification.
Claims (5)
1. an oxymetazoline hydrochloride eye drop, it is characterised in that including:
Oxymetazoline hydrochloride；And
Pharmaceutically acceptable adjuvant.
Oxymetazoline hydrochloride eye drop the most according to claim 1, it is characterised in that described pharmaceutically acceptable auxiliary
Material is at least one in osmotic pressure regulator, thickening agent, freshener, antibacterial, acid-base modifier and ethanol.
Oxymetazoline hydrochloride eye drop the most according to claim 2, it is characterised in that including: oxymetazoline hydrochloride
2.5 weight portions, osmotic pressure regulator 90 weight portion, thickening agent 10-100 weight portion, freshener 1-2 weight portion, antibacterial
0.5-1 weight portion, acid-base modifier is appropriate, appropriate amount of ethanol.
Oxymetazoline hydrochloride eye drop the most according to claim 3, it is characterised in that described osmotic pressure regulator is choosing
At least one in sodium chloride, potassium chloride, disodium hydrogen phosphate, sodium dihydrogen phosphate, boric acid, Borax, glycerol and glucose,
Preferably osmotic pressure regulator is sodium chloride；
Described thickening agent be in polyvinyl alcohol, hypromellose, hyaluronic acid sodium, polyvidone and Polyethylene Glycol at least
One, preferred thickener is at least one in polyvinyl alcohol, hypromellose and Polyethylene Glycol；
Described freshener be at least one in Herba Menthae and Borneolum Syntheticum, preferably freshener be the combination of Borneolum Syntheticum and Herba Menthae, more excellent
Elect Borneolum Syntheticum and the combination of Herba Menthae in mass ratio 3: 1 as；
Described antibacterial is to prick selected from Benasept, ethyl hydroxybenzoate, ethyl hydroxybenzoate, chlorobutanol, benzalkonium chloride, benzene
At least one in bromine ammonium, sorbic acid and benzoic acid, preferably antibacterial are at least one in benzalkonium bromide and sorbic acid；
Described acid-base modifier is at least in hydrochloric acid, boric acid, citric acid, sodium hydroxide, Borax and sodium citrate
Kind, preferably acid-base modifier is sodium hydroxide.
5. prepare the method for oxymetazoline hydrochloride eye drop described in any one in claim 1-4 for one kind, it is characterised in that
Including:
(1) by described oxymetazoline hydrochloride, osmotic pressure regulator, antibacterial mixing, injection is joined to the mixture obtained
With water, after stirring to dissolving, heat up and boil 15-30min, be cooled to room temperature, obtain the first solution；
(2) freshener is dissolved in ethanol in proper amount, stirs, obtain the second solution；
(3) described first solution and described first solution are mixed, obtain the 3rd solution；
(4) in described 3rd solution, add viscosifier, stir, utilize acid-base modifier to adjust pH value to be 4.0-5.0,
Constant volume, obtains the 4th solution；
(5) use the microporous membrane of 0.45um that described 4th solution is filtered, in order to obtain described oxymetazoline hydrochloride and drip
Ocular fluid.
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