CN107854470A - Alcaftadine composition, preparation method and use - Google Patents
Alcaftadine composition, preparation method and use Download PDFInfo
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- CN107854470A CN107854470A CN201610846751.4A CN201610846751A CN107854470A CN 107854470 A CN107854470 A CN 107854470A CN 201610846751 A CN201610846751 A CN 201610846751A CN 107854470 A CN107854470 A CN 107854470A
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- 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
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
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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
- A61K47/34—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
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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
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- A—HUMAN NECESSITIES
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- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0048—Eye, e.g. artificial tears
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- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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Abstract
This application discloses a kind of Alcaftadine composition, the Alcaftadine composition contains 0.005 10% (w/v) Alcaftadine, 0.001 10% (w/v) nonionic surfactant and other appropriate pharmaceutically acceptable excipient and water for injection.Said composition is not while main ingredient Alcaftadine Excess quantities are increased, it can ensure that Alcaftadine fully dissolves in aqueous, and can improves the stability of Alcaftadine in aqueous, and compared with commercially available eye drops, the eye drops of prescription of the present invention is not irritant, and security is good.It is this method rational technology, simple and easy disclosed herein as well is the preparation method of the Alcaftadine composition.
Description
Technical field
The application is related to a kind of Alcaftadine composition, belongs to technical field of pharmaceuticals.
Technical background
Allergic conjunctivitis is also known as allergic conjunctivitis, is that conjunctiva is super to one kind caused by extraneous allergen quick anti-
Should.Mainly include type Ⅰ allergy and type Ⅳ allergy, wherein most normal with the allergic conjunctivitis caused by type Ⅰ allergy
See.Allergic conjunctivitis caused by type Ⅰ allergy is in anaphylactic type, and referring mainly to allergic conjunctivitis includes seasonal allergic knot
Film inflammation, perennial allergic conjunctivitis, macropapillary conjunctivitis, vernal keratoconjunctivitis, atopy keratoconjunctivitis sicca etc.；IV type is abnormal
Allergic conjunctivitis caused by reaction is in delayed, mainly there is phlycenular conjunctivitis.
The most common symptom of allergic conjunctivitis is that eye is itched, and almost all of allergic conjunctivitis patient may occur in which, but
Eye is itched not its distinctive symptom, and the allergic conjunctivitis eye of different subtype is itched degree difference, and wherein vernal keratoconjunctivitis is usual
Performance is the most obvious, and other more typical symptoms are shed tears, burning heat sensation, and photophobia and secretion increase etc., secretion is mostly mucus
Property, sometimes may be used in sticky thread, some more serious allergic conjunctivitises, such as vernal keratoconjunctivitis and atopy keratoconjunctivitis sicca
To there is visual impairment.
If allergic conjunctivitis is treated not in time, easy recurrent exerbation, the life to people brings various troubles：Such as (1)
When allergic conjunctivitis breaks out, patient can feel that eye is very itched incomparably, cause patient's notice not concentrate, have a strong impact on people
Work and life.Therefore children can then influence school work.(2) patient's vision is influenceed, in general allergic conjunctivitis is to eyesight
Anything will not be caused to influence, it is most of to fully recover in a short time, but some vernal keratoconjunctivitises and atopic conjunctivitis can be sent out
Raw corneal complication even endangers eyesight, and severe patient may result in blindness.(3) quality of life of people is influenceed.Due to allergy
The symptom such as itch, pain, oedema caused by membranous conjunctivitis.Influence whether psychology and the life of patient.Cause patient and its family
The reduction of living quality of patients.(4) other anaphylactias can be triggered.Allergic conjunctivitis patient has due to being allergic constitution
Probably due to allergic conjunctivitis and trigger other anaphylactias such as allergic rhinitis, allergic asthma, more aggravated patient
Burden.(5) strictly speaking, the other positions for being not only allergic conjunctivitis, also affecting eyes that allergic reaction triggers,
So as to there is more illness in eye to show, some consequences are also more serious.
Alcaftadine is released as a kind of three ring histamine H 1 receptor antagonists and mast cell stabilizers, inhibited mast cell
Put histamine and prevent histamine from acting on, so as to mitigate allergic reaction.Reduce chemotaxis in addition, Alcaftadine also has, suppress thermophilic eosin
Cytoactive acts on.This causes a variety of allergy symptoms such as Alcaftadine rubescent to eyes, chemosis and eyelid swelled
Therapeutic effect will be substantially due to other similar drugs.The structural formula of Alcaftadine is as follows：
External clinical studies show, patient use 0.25% Alcaftadine eye drops, once a day, can reduce anaphylaxis
Eye caused by conjunctivitis is red and swollen.The eye drops is sold and used European and American developed countries are granted at present, Clinical practice
Safer, toxic side effect is small, and patient compliance is good.
It is well known that the process for preparation of eye drops, which will typically pass through filter membrane, carries out filtration sterilization, and it is necessary step.Research
It was found that Alcaftadine is insoluble drug, it is almost insoluble in water.And dissolve incomplete Alcaftadine and be easy to filtering
During by membrane retention or absorption, it is unqualified so as to cause final decoction content seriously to reduce.Although increase can be passed through
Inventory and raising solution temperature are made up, but can cause the waste of raw material and the increase about content of material, while
Production cost can be greatly increased.In addition, the Alcaftadine aqueous solution is also unstable, it is especially more unstable under the conditions of light and heat photograph
It is fixed.Also certain degradation impurity can be produced during the storage and placement in the aqueous solution of Alcaftadine, and these are degraded
The presence of impurity can influence the toxicological profile of said preparation.
Therefore, in order to overcome the drawbacks described above in the presence of prior art, spy proposes this invention.
The content of the invention
The present inventor has found in Alcaftadine eye drops formulation study and development process, is containing nonionic table
In the case of the activating agent of face, the solubility of Alcaftadine greatly improves, and can be completely dissolved under normal circumstances, and this solves preparation
During Excess quantities and caused by wastage of material the problem of.In addition, inventors have also discovered that, add nonionic surfactant
Manufactured Alcaftadine eye drops is more more stable than not adding the Alcaftadine eye drops of nonionic surfactant, improves Ah Ka
He determines the stability of eye-drops preparations.
Therefore, according to an aspect of the invention, there is provided a kind of Alcaftadine composition, said composition are not increasing master
While the inventory of medicine Alcaftadine, it can ensure that Alcaftadine fully dissolves in aqueous, and can improves Alcaftadine
Stability in aqueous, so as to reach the purpose for safely, effectively treating allergic conjunctivitis correlation itch.
To achieve these goals, the application adopts the following technical scheme that：
A kind of Alcaftadine composition, the Alcaftadine composition contain 0.005-10% (w/v) Alcaftadine and
0.001-10% (w/v) nonionic surfactant.
Preferably, 0.1-0.4% (w/v) Alcaftadine and 0.05-5% (w/ is contained in the Alcaftadine composition
V) nonionic surfactant.
It is highly preferred that Alcaftadine and 0.5% (w/v) containing 0.25% (w/v) in the Alcaftadine composition
Nonionic surfactant.
Preferably, the Alcaftadine composition also includes solvent and except the other of nonionic surfactant pharmaceutically may be used
The excipient of receiving.
Involved percentage composition (w/v) refers to weight and volume ratio in the application, is the application Ah Ka in particular
He determines each component weight (g) and cumulative volume (mL) percentage of final solution in composition.
Preferably, the nonionic surfactant is HS15.
Preferably, described pharmaceutically acceptable excipient includes osmotic pressure regulator, bacteriostatic agent, stabilizer and solvent
At least one of.
Preferably, the osmotic pressure regulator is included in sodium chloride, glucose, mannitol, glycerine, propane diols and boric acid
It is at least one.
Preferably, the bacteriostatic agent includes methyl p-hydroxybenzoate, ethyl-para-hydroxybenzoate, P-hydroxybenzoic acid third
Ester, phenmethylol, benzyl carbinol, sorbic acid, salicylic acid, anesin, benzalkonium chloride, benzalkonium bromide, thimerosal or Phenoxyethanol
At least one of.
Preferably, the solvent includes water for injection.
Preferably, the Alcaftadine composition specifically includes benzalkonium chloride, sodium dihydrogen phosphate, sodium chloride, edetic acid(EDTA) two
Sodium and water for injection.
It is highly preferred that concentration of the benzalkonium chloride in the Alcaftadine composition is 0.001-0.01% (w/v)
Benzalkonium chloride, concentration of the sodium dihydrogen phosphate in the Alcaftadine composition are 0.3-0.8% (w/v), the chlorination
Concentration of the sodium in the Alcaftadine composition is 0.3-0.8% (w/v), the natrium adetate in the Alcaftadine group
Concentration in compound is 0.005-0.02% (w/v).
Most preferably, the Alcaftadine composition by 0.25% (w/v) Alcaftadine, 0.5% (w/v) polyethylene glycol-
12- hydroxy stearic acid esters, 0.005% (w/v) benzalkonium chloride, 0.54% (w/v) sodium dihydrogen phosphate, 0.62% (w/v) sodium chloride,
0.01% (w/v) natrium adetate, and water for injection composition.
Preferably, the pH most 6.0-7.0 of the Alcaftadine composition.
In addition, the other pharmaceutically acceptable excipient being previously mentioned in the Alcaftadine composition of the application can also wrap
Containing other usual components in such as eye-drops preparations such as tackifier, antioxidant.
Tackifier may be selected from methylcellulose, sodium carboxymethylcellulose, hydroxyethyl cellulose, hydroxypropyl methyl cellulose,
At least one of PVP, polyethylene glycol and polyvinyl alcohol.
Antioxidant may be selected from vitamin C, vitamin E, sodium hydrogensulfite, sodium pyrosulfite, sodium thiosulfate, sulfurous acid
At least one of sodium, citric acid, tartaric acid, lecithin and amino acid.
According to another aspect of the present invention, there is provided a kind of preparation method of Alcaftadine composition, this method technique are closed
Manage, be simple and easy.
To achieve these goals, the application adopts the following technical scheme that：
A kind of preparation method of Alcaftadine composition, methods described comprise the following steps：
(1) Alcaftadine, the nonionic surfactant and the first solvent are mixed, and makes the Alcaftadine
Fully dissolving, obtains solution I, the water for injection is preferably water for injection；
(2) optionally other pharmaceutically acceptable carriers are dissolved in the second solvent, obtain solution II；Wherein, it is described
First solvent and the second solvent are identical or different；
(3) in the case where step (2) be present, the solution I and the solution II is mixed, obtain solution III,
The solution I obtained in the step (1) or the solution III obtained in the step 3) are carried out sterile
Processing, obtains the composition.
Preferably, filtered using 0.2 μm -0.45 μm of miillpore filter and carry out aseptic process.
Most preferably, filtered using 0.2 μm -0.22 μm of miillpore filter and carry out aseptic process.
The preparation method of preferably described Alcaftadine composition specifically comprises the following steps：
(1) nonionic surfactant is dissolved in water for injection, adds recipe quantity Alcaftadine, fill it
Divide dissolving complete, obtain the solution I；
(2) appropriate water for injection is separately taken, after being heated to its boiling, pharmaceutically acceptable excipient is dissolved in wherein,
Being subject to stirring makes it fully dissolve, and obtains the solution II；
(3) solution II is cooled to after room temperature and merged with solution I, and add water for injection, obtain the solution III；
(4) pH value of the solution III is adjusted to 6.0-7.0, and described Ah Ka is produced after 0.22 μm of filtering with microporous membrane
He determines composition.
In step (3), add water for injection to full dose and refer to add water for injection so that Alcaftadine composition reaches rule
Fixed cumulative volume.
According to the another further aspect of the application, there is provided Alcaftadine composition is being prepared for treating and/or preventing eyes
The clinical symptoms or the mechanistic disease related to eyes allergy and/or ocular inflamation of allergy and/or ocular inflamation
Application in the medicine of shape, wherein the symptom is selected from rubescent allergic conjunctivitis, itching eyes, eyes, eyelid swelled, conjunctiva
Oedema, shed tears, rhinitis, nasal congestion, rhinorrhea, ear itch, palate itch, sneezing, Vascular permeability, conjunctival epithelial tight combine
At least one of integrality reduction, mast cell degradation.
Preferably, the Alcaftadine composition is prepared into eye drops or gel for eye use, is preferably prepared to eye drops.
Beneficial effect caused by the application energy includes but is not limited to：
1) Alcaftadine composition provided herein, 0.005-10% (w/ are contained in the Alcaftadine composition
V) Alcaftadine, 0.001-10% (w/v) nonionic surfactants and appropriate pharmaceutically acceptable excipient and injection
Water.The present inventor Alcaftadine composition prescription study during find, particularly by 0.5% (w/v) it is non-from
Sub- surfactant HS15 is added in Alcaftadine composition, and Alcaftadine can be completely molten
Solution, dissolubility greatly improves, solve the problems, such as Excess quantities in preparation process and caused by wastage of material.It is in addition, of the invention
People is, it was also found that add Alcaftadine made of 0.5% (w/v) nonionic surfactant HS15
Eye drops is more more stable than not adding the commercially available Alcaftadine eye drops of nonionic surfactant.Thus illustrate provided herein
Alcaftadine composition it is higher than the stability of Alcaftadine eye-drops preparations of the prior art.
2) preparation method of Alcaftadine composition provided herein, there is the characteristics of rational technology, simple and easy；
Caused impurity in preparation process or storage process can also be substantially reduced simultaneously, increases its stability, so as to reach raising product
Quality and the beneficial effect for improving curative effect.
3) Alcaftadine composition provided herein is preparing treatment allergic conjunctivitis and related eye itch medicine
The purposes of aspect, it can be seen from experimental result, after multiple dosing, Alcaftadine composition is nonirritant；And with commercially available Ah
Catarrh is determined eye drops and compared, and does not increase excitant, illustrates that the security of Alcaftadine composition provided herein is good.
Specific embodiment
The application is described in detail with reference to embodiment, but the application is not limited to these embodiments.
Unless otherwise instructed, the raw material Alcaftadine in embodiments herein is application number according to number of patent application
201510448367.4 synthesis is prepared in method in, and remaining auxiliary material is commercially available by commercial sources.
Embodiment 1
The preparation method of Alcaftadine composition：
(1) nonionic surfactant is weighed by recipe quantity, it is dissolved in water for injection, add recipe quantity Ah Ka
He is fixed, is stirred to dissolve completely, obtains solution I；
(2) appropriate water for injection is separately taken, after being heated to its boiling, pharmaceutically acceptable tax is dissolved in wherein, is subject to
It is stirred to dissolve completely, obtains solution II；
(3) solution II is cooled to after room temperature and merged with solution I, and add water for injection to full dose, obtain solution
Ⅲ；
(4) pH value of solution III is adjusted to 6.0-7.0, and described Alcaftadine is produced after 0.22 μm of filtering with microporous membrane
Composition.
The concrete composition of Alcaftadine composition, it is as shown in the table：
Embodiment 2
Different Alcaftadine eye drops is prepared according to following prescription and preparation technology, and using the detection filtering of HPLC methods
Front and rear Alcaftadine content：
Preparation technology：
(1) nonionic surfactant is weighed by recipe quantity, it is dissolved in water for injection, add recipe quantity Ah Ka
He is fixed, is stirred to dissolve completely, obtains solution I；
(2) appropriate water for injection is separately taken, after being heated to its boiling, pharmaceutically acceptable tax is dissolved in wherein, is subject to
It is stirred to dissolve completely, obtains solution II；
(3) solution II is cooled to after room temperature and merged with solution I, and add water for injection to full dose, obtain solution
Ⅲ；
(4) pH value of solution III is adjusted to 6.0-7.0, and described Alcaftadine is produced after 0.22 μm of filtering with microporous membrane
Composition.
Table 1：Composition and measurement result
Conclusion：The prescription 13 of nonionic surfactant is not added with it can be seen from above-mentioned result of the test in miillpore filter
Content is relatively low before filtering and content has also declined after filtering, and illustrate that main ingredient is not completely dissolved, and envelope section after filtration
Stay；In addition, add the prescription 7 of nonionic surfactant HS15 (Solutol HS 15)
Content does not change substantially before and after filtering with microporous membrane, and illustrating main ingredient, fully dissolving is complete, with adding other nonionic tables
The prescription of face activating agent is compared, and the content of Alcaftadine declines less afterwards before filtration, illustrates polyethylene glycol -12- hydroxy stearates
Hydrotropy effect of the acid esters (Solutol HS 15) to Alcaftadine is more stronger than other nonionic surfactants thus preferably poly-
Cosolvent of the ethylene glycol -12- hydroxy stearic acid esters (Solutol HS 15) as Alcaftadine eye drops.
The nonionic surfactant HS15 of embodiment 2 (Solutol HS 15) is to Ah Ka
He determines the experiment of eye drops stability influence
Configured sample by the prescription 7 in above-described embodiment 1, and pressed commercially available back, at the same with commercial samples Lastacaft
(Alcaftadine) eye drops (being free of surfactant Solutol HS 15) is placed together, carries out influence factor experiment and stably
Property experiment investigation.As a result 2 and table 3 be see the table below：
Table 2：Prescription 7 and commercial samples influence factor experiment investigation result in the embodiment of the present invention 1
Table 3：From grinding prescription and commercial samples stability test testing result
Influence factor and stability test result are shown, according to Alcaftadine eye drops pH value, the property for grinding prescription preparation certainly
Shape, visible foreign matters, relevant material, content etc. meet regulation, and commercial preparation relevant material in placement process increases substantially,
Illustrate to the addition of nonionic surfactant HS15 (Solutol HS 15) grinds prescription system certainly
The stability of agent will be apparently higher than the commercial samples for being not added with nonionic surfactant.
The Alcaftadine eye drops toxicology test of embodiment 3
First, test objective
This experiment passes through Alcaftadine eye drops test specimen multiple dosing eye irritant test (28 days), observes Alcaftadine
Eye drops given the test agent reacts total mark according to its Eye irritation and tissue pathology checking ties to rabbit eyes irritative response situation
Fruit, assess its Eye irritation extent of reaction.
2nd, test specimen
Sample is prepared by prescription 7 in above-described embodiment 1, by commercially available back, specification is：3.0ml (trial-production).
According to《Chinese Pharmacopoeia》Require to carry out under 2010 editions two annex eye drops items drug content, relevant content of material,
PH value, visible foreign matters, visual examination be it is up-to-standard after test specimen.
3rd, test method and process
From qualified regular grade rabbit 4 of quarantining, using androgynous right and left eyes self-contrast method, the capacity such as left eye is given listing
Product is control, and right eye gives the sample of prescription 7 configured in embodiment 1.By clinical administration, 1 time a day, 1 drips every time
(50 μ l), continuous eye drip is given
Medicine 28 days.Eye was examined in 1,2,4,24,48 and 72 hour before observation daily administration and after last time administration
Look into, standards of grading are reacted according to Eye irritation and eye irritation evaluation criterion evaluates the Eye irritation of Alcaftadine eye drops test specimen
Intensity.Eye irritation reaction score criteria is shown in Table 4.
The Eye irritation of table 4 reacts score criteria
The stimulate the reaction score value of the cornea of each observing time each animal, iris and conjunctiva is added always long-pending
Point, then the last score value of the group is produced to integrate summation divided by number of animals, and judge that it stimulates degree by table 3.Eye irritation is evaluated
Standard is shown in Table 5.
The eye irritation evaluation criterion of table 5
| Score value | Evaluation |
| 0-3 | It is nonirritant |
| 4-8 | Slight stimulation |
| 9-12 | Moderate excitant |
| 13-16 | Severe excitant |
4th, result of the test
Eye was checked in 1,2,4,24,48 and 72 hour before daily administration and after last time administration, 4 tested families
Rabbit eyes are showed no obvious Eye irritation symptom, and each eye is compared to each other without significant difference with comparison before experiment and bilateral, stimulated
Reaction scoring is as shown in table 6.
The Alcaftadine eye drops of table 6 reacts grade form to Eye irritation before experiment rabbit daily administration
Continued 6
5th, conclusion (of pressure testing)
To testing result with score value statistical calculations, it is found that the sample of prescription 7 is after multiple dosing in the embodiment of the present invention 1,
It is nonirritant；And compared with commercially available eye drops, do not increase excitant, illustrate that the security of prescription of the present invention is good.
It is described above, only it is several embodiments of the application, any type of limitation is not done to the application, although this Shen
Please with preferred embodiment disclose as above, but and be not used to limit the application, any person skilled in the art, do not taking off
In the range of technical scheme, make a little variation using the technology contents of the disclosure above or modification is equal to
Case study on implementation is imitated, is belonged in the range of technical scheme.
Claims (10)
- A kind of 1. Alcaftadine composition, it is characterised in that the Alcaftadine composition contain 0.005-10% (w/v) Ah Catarrh determines and 0.001-10% (w/v) nonionic surfactant；It is preferred that contain 0.1- in the Alcaftadine composition 0.4% (w/v) Alcaftadine and 0.05-5% (w/v) nonionic surfactant；More preferably described Alcaftadine combination Alcaftadine containing 0.25% (w/v) and 0.5% (w/v) nonionic surfactant in thing.
- 2. Alcaftadine composition according to claim 1, it is characterised in that the Alcaftadine composition also includes molten Agent and other pharmaceutically acceptable excipient except nonionic surfactant.
- 3. Alcaftadine composition according to claim 1 or 2, it is characterised in that the nonionic surfactant is HS15.
- 4. the Alcaftadine composition according to any one in claim 1-3, it is characterised in that described pharmaceutically may be used The excipient of receiving includes at least one of osmotic pressure regulator, bacteriostatic agent, stabilizer and buffer.
- 5. the Alcaftadine composition according to any one in claim 1-4, it is characterised in that the solvent includes note Penetrate and use water.
- 6. the Alcaftadine composition according to any one in claim 1-5, it is characterised in that the Alcaftadine group Compound also includes benzalkonium chloride, sodium dihydrogen phosphate, sodium chloride, natrium adetate and solvent；It is preferred that the benzalkonium chloride is described Concentration in Alcaftadine composition is 0.001-0.01% (w/v), the sodium dihydrogen phosphate is in the Alcaftadine composition In concentration be that the concentration of 0.3-0.8% (w/v), the sodium chloride in the Alcaftadine composition is 0.3-0.8% (w/ V), concentration of the natrium adetate in the Alcaftadine composition is 0.005-0.02% (w/v)；Most preferably Ah Catarrh determines composition by 0.25% (w/v) Alcaftadine, 0.5% (w/v) HS15,0.005% (w/v) benzalkonium chloride, 0.54% (w/v) sodium dihydrogen phosphate, 0.62% (w/v) sodium chloride, 0.01% (w/v) natrium adetate, Formed with water for injection.
- 7. the preparation method of Alcaftadine composition described in any one in claim 1-6, it is characterised in that methods described bag Include following steps：(1) Alcaftadine, the nonionic surfactant and the first solvent are mixed, and makes the Alcaftadine abundant Dissolving, obtains solution I, the solvent is preferably water for injection；(2) optionally other pharmaceutically acceptable carriers are dissolved in the second solvent, obtain solution II；Wherein, described first Solvent and the second solvent are identical or different；(3) in the case where step (2) be present, the solution I and the solution II is mixed, obtain solution III,Sterile place is carried out to the solution I obtained in the step (1) or the solution III obtained in the step 3) Reason, obtains the composition；Carry out aseptic process it is preferred that being filtered using 0.2 μm -0.45 μm of miillpore filter；Most preferably with 0.2 μm -0.22 μm of miillpore filter, which is filtered, carrys out aseptic process.
- 8. preparation method according to claim 7, it is characterised in that methods described specifically comprises the following steps：(1) nonionic surfactant is dissolved in water for injection, adds recipe quantity Alcaftadine, make it fully molten Solution, obtains the solution I；(2) appropriate water for injection is separately taken, after being heated to its boiling, pharmaceutically acceptable excipient is dissolved in wherein, is subject to Stirring makes it fully dissolve, and obtains the solution II；(3) solution II is cooled to after room temperature and merged with solution I, and add water for injection, obtain the solution III；(4) pH value of the solution III is adjusted to 6.0-7.0, and described Alcaftadine is produced after 0.22 μm of filtering with microporous membrane Composition.
- 9. Alcaftadine composition in claim 1-6 described in any one and/or according to the methods described of claim 7 or 8 The Alcaftadine composition of preparation is used to treat and/or prevents eyes allergy and/or the clinical condition of ocular inflamation preparing Application in the medicine of shape or the mechanistic symptom related to eyes allergy and/or ocular inflamation, wherein the symptom Selected from allergic conjunctivitis, itching eyes, eyes are rubescent, eyelid swelled, chemosis, shed tears, rhinitis, nasal congestion, rhinorrhea, In ear itch, palate itch, sneezing, Vascular permeability, the integrality reduction of conjunctival epithelial tight combination, mast cell degradation extremely Few one kind.
- 10. application according to claim 9, it is characterised in that by the Alcaftadine composition be prepared into eye drops or Gel for eye use, it is preferably prepared to eye drops.
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| CN201610846751.4A CN107854470B (en) | 2016-09-21 | 2016-09-21 | Acatadine composition, preparation method and application thereof |
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| CN107854470B CN107854470B (en) | 2020-03-27 |
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| CN201610846751.4A Active CN107854470B (en) | 2016-09-21 | 2016-09-21 | Acatadine composition, preparation method and application thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN115671042A (en) * | 2022-10-24 | 2023-02-03 | 江苏汉晨药业有限公司 | Acatadine eye drops |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101460176A (en) * | 2006-03-31 | 2009-06-17 | 维斯塔肯药品有限责任公司 | Ocular allergy treatments |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101460176A (en) * | 2006-03-31 | 2009-06-17 | 维斯塔肯药品有限责任公司 | Ocular allergy treatments |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115671042A (en) * | 2022-10-24 | 2023-02-03 | 江苏汉晨药业有限公司 | Acatadine eye drops |
| CN115671042B (en) * | 2022-10-24 | 2024-07-23 | 江苏汉晨药业有限公司 | Acartadine eye drops |
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| CN107854470B (en) | 2020-03-27 |
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