CN104491876A - Sodium hyaluronate-containing epinastine eye drops and preparation method thereof - Google Patents
Sodium hyaluronate-containing epinastine eye drops and preparation method thereof Download PDFInfo
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- CN104491876A CN104491876A CN201410820214.3A CN201410820214A CN104491876A CN 104491876 A CN104491876 A CN 104491876A CN 201410820214 A CN201410820214 A CN 201410820214A CN 104491876 A CN104491876 A CN 104491876A
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Abstract
The invention relates to sodium hyaluronate-containing epinastine eye drops and a preparation method thereof. According to the sodium hyaluronate-containing epinastine eye drops, the content of epinastine hydrochloride is 0.05-0.5 percent, the content of the sodium hyaluronate is 0.01-0.5 percent, and a pH value is controlled to be 4.0-7.5; as the sodium hyaluronate is selected, detention time of a medicament in eyes can be prolonged, and the bioavailability is improved.
Description
Technical field
The present invention relates to a kind of epinastine hydrochloride eye drop containing hyaluronic acid sodium and preparation method thereof
Background technology
Anaphylaxis conjunctivitis is the common eye table anaphylactic disease of a class, and it is mainly caused by I type and IV allergic reaction type.This sick topmost symptom is ophthalmic pruritus, often with conjunctival congestion, edema and the sign such as nipple, follicle hypertrophy.According to clinical manifestation, the course of disease and prognosis difference, anaphylaxis conjunctivitis can be divided into 5 types: seasonal allergic conjunctivitis, perennial allergic conjunctivitis, vernal keratoconjunctivitis, macropapillary conjunctivitis and atopy keratoconjunctivitis.Its prevalence is about 20% of total population, and China's anaphylaxis conjunctivitis is apt to occur in the young and the middle aged, with perennial allergic conjunctivitis and seasonal allergic conjunctivitis for main Types.Common drug clinically for anaphylaxis conjunctivitis has: (1) antihistaminic; (2) mast cell stabilizers; (3) economic benefits and social benefits medicine; (4) NSAID (non-steroidal anti-inflammatory drug); (5) glucocorticoids; (6) immunosuppressant.
Epinastine hydrochloride (Epinastine hydrochloride) is second filial generation antihistaminic, has the effect of Selective depression peripheral H1-receptor, without maincenter sedation and cholinolytic effect.Clinically be used for treatment of allergic rhinitis, eczema, urticaria, dermatitis, skin pruritus, psoriasis, allergic bronchial asthma etc.Its clinical efficacy and side effect aspect are better than other Claritins such as diphenhydramine, promethazine, chlorphenamine, cetirizine.Epinastine hydrochloride is used for anaphylaxis conjunctivitis, and improving, curative effect in ophthalmic pruritus and conjunctival congestion is very good, and can not increase the danger of ocular surface injury and xerophthalmia.
Epinastine hydrochloride eye drop (trade name: Elestat) is developed by Allergan company of the U.S., goes on the market abroad, be used for the treatment of anaphylaxis conjunctivitis in 2004.But owing to causing overflow of drug fluid to run off by tear dilution, nasolacrimal duct excretion etc. after this eye drop medication, the bioavailability of eye is lower, and the time of effect is also very of short duration.In order to extend the action time of eye drop, improving bioavailability, improving therapeutic effect, can add viscosifier in common eye drop preparation prescription, increase the viscosity of eye drop, prolong drug in the holdup time of eye, thus improves the bioavailability of medicine.Viscosifier conventional in preparation have such as carbomer, poloxamer, hypromellose etc.But in these adjuvants: carbomer gel is met salt electrolyte viscosity and can be declined, and carbomer can cause blurred vision; Poloxamer is unstable to responsive to temperature; The synthesising macromolecule copolymers such as hypromellose, its solution belongs to Newtonian fluid, has pain during nictation.Therefore, these viscosifier above are scarcely suitable for preparing eye drop.
In sum, this area can delay overflow of drug fluid loss, the epinastine hydrochloride eye drop of prolong drug holdup time in the urgent need to developing one.
Summary of the invention
For the problems referred to above, applicant has done large quantifier elimination, finally finds that in epinastine hydrochloride eye drop, add hyaluronic acid sodium can solve the problem.Hyaluronic Acid also known as hyaluronic acid, be a kind of be extensively present in body respectively organize in mucopolysaccharide, there is good biocompatibility, viscosifying action, bioadhesion and spreading wetting ability.In addition, hyaluronic acid sodium and epinastine hydrochloride, with opposite charges, can form ion pair thus promote that medicine is in the delay of eye.
The object of this invention is to provide a kind of epinastine hydrochloride eye drop containing hyaluronic acid sodium, it can increase the viscosity of eye drop, and prolong drug in the holdup time of eye, thus improves the bioavailability of medicine at eye.
Eye drop of the present invention is made up of active constituents of medicine, viscosifier, antioxidant, isoosmotic adjusting agent, pH adjusting agent, buffer salt, antiseptic and water for injection.
In eye drop of the present invention, each composition weight percentage composition is:
The relative molecular mass Mr=10 ten thousand-400 ten thousand of hyaluronic acid sodium of the present invention.
Buffer salt of the present invention is Acetic acid-sodium acetate buffer or citric acid-sodium citrate buffer.
Isoosmotic adjusting agent of the present invention is one or more in sodium chloride and glucose.
Appropriate pH adjusting agent of the present invention makes eye drop pH to 4.0-7.5.
Antiseptic of the present invention is selected from one or more in benzalkonium chloride, benzalkonium bromide, methyl hydroxybenzoate, ethyl hydroxybenzoate or propyl hydroxybenzoate.
PH adjusting agent of the present invention is selected from one or more in sodium hydroxide and hydrochloric acid.
The preparation method of eye drop of the present invention, step comprises: add epinastine hydrochloride, buffer salt, isoosmotic adjusting agent, EDTA-2Na dissolving in water for injection after, add the swelling solution of hyaluronic acid sodium completely again, after stirring, add pH adjusting agent, filter fill.
The usage and dosage of eye drop of the present invention: 1, every side one time, 2 times on the one.
The feature of eye drop of the present invention is: viscosity increase can prevent overflow of drug fluid to run off, and makes medicine be detained focal zone for a long time, thus improves the bioavailability of medicine.
Detailed description of the invention
Hereafter will elaborate to the present invention in conjunction with example, but these concrete examples are not intended to limit the present invention.
The preparation of embodiment 1 epinastine hydrochloride eye drop
Comprise in 100mL water for injection:
Preparation method: add epinastine hydrochloride, sodium dihydrogen phosphate, sodium chloride, disodiumedetate, benzalkonium chloride dissolving in water for injection after, add the swelling solution of hyaluronic acid sodium completely again, add acid or alkali adjustment pH to 7.0 after stirring, filter fill.
The preparation of embodiment 2 epinastine hydrochloride eye drop
Comprise in 100mL water for injection:
Preparation method: with the preparation method of embodiment 1
The preparation of embodiment 3 epinastine hydrochloride eye drop
Comprise in 100mL water for injection:
Preparation method: with the preparation method of embodiment 1
The mensuration of embodiment 4 epinastine hydrochloride eye drop viscosity
Measure the viscosity of embodiment 1, embodiment 2 and embodiment 3 eye drop respectively.Result is as shown in table 1:
The viscosity of table 1 epinastine hydrochloride eye drop
Embodiment 5 lagophthalmos lacrimal pharmacokinetics is tested
Sample:
1) matched group: epinastine hydrochloride eye drop listing preparation (trade name: Elestat); Test group: embodiment 1, embodiment 2, embodiment 3
2) experimental technique: healthy new zealand white rabbit, female, body weight 1.5-2.0kg, is divided into 4 groups at random, often organizes 3.Eye drop 50 μ L is dripped respectively in rabbit conjunctival capsule.After eye drip in 15,30,60,90,120,180,240, capillary tube is placed in eyelid by 360min, draw tear 10 μ L, be placed in plastic centrifuge tube, add 90 μ L methanol vortex 2min, the centrifugal 10min of 10000rpm, get supernatant 20 μ 1 sample introduction HPLC to analyze, calculate the tear fluid concentration of epinastine hydrochloride.The pharmacokinetic parameters area under the drug-time curve (AUC) that statistics moments method calculates and mean residence time (MRT), data are as shown in table 2:
The pharmacokinetic parameters of table 2 epinastine hydrochloride eye drop in rabbit tear
Result shows, all test group AUC and MRT compared with matched group all has significant difference (P < 0.05), and in test group, the AUC of embodiment 1, embodiment 2, embodiment 3 is respectively 3.2 times, 6.1 times, 6.4 times of control group A UC.This shows that adding of hyaluronic acid sodium can the holdup time of prolong drug in tear, thus improves the bioavailability of medicine at eye.
Claims (8)
1. an eye drop, comprises following component and content:
All percent is percetage by weight.
2. eye drop as claimed in claim 1, is characterized in that the relative molecular mass Mr=10 ten thousand-400 ten thousand of described hyaluronic acid sodium.
3. eye drop as claimed in claim 1, is characterized in that described buffer salt is phosphate buffer or citrate buffer.
4. eye drop as claimed in claim 1, is characterized in that described isoosmotic adjusting agent is one or more in sodium chloride and glucose.
5. eye drop as claimed in claim 1, is characterized in that described appropriate pH adjusting agent makes eye drop pH to 4.0-7.5.
6. eye drop as claimed in claim 1, is characterized in that one or more that described antiseptic is selected from benzalkonium chloride, benzalkonium bromide, methyl hydroxybenzoate, ethyl hydroxybenzoate or propyl hydroxybenzoate.
7. eye drop as claimed in claim 1, is characterized in that one or more that described pH adjusting agent is selected from sodium hydroxide and hydrochloric acid.
8. the preparation method of eye drop as described in claim 1-5, step comprises: add epinastine hydrochloride, buffer salt, isoosmotic adjusting agent, disodiumedetate, antiseptic dissolving in water for injection after, add the swelling solution of hyaluronic acid sodium completely again, add pH adjusting agent after stirring and regulate pH to 4.0-7.5, filter fill.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201410820214.3A CN104491876A (en) | 2014-12-23 | 2014-12-23 | Sodium hyaluronate-containing epinastine eye drops and preparation method thereof |
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| CN201410820214.3A CN104491876A (en) | 2014-12-23 | 2014-12-23 | Sodium hyaluronate-containing epinastine eye drops and preparation method thereof |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2020125318A (en) * | 2017-05-01 | 2020-08-20 | 参天製薬株式会社 | Eye drop |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1292752C (en) * | 1999-11-12 | 2007-01-03 | 贝林格尔·英格海姆国际有限公司 | Solutions containing epinastine |
| CN100998863A (en) * | 2006-01-12 | 2007-07-18 | 上海新药研究开发中心 | N-acetyl carnosine eye drops for preventing and treating cataract and its preparation method |
| CN102670493A (en) * | 2012-05-22 | 2012-09-19 | 宁夏康亚药业有限公司 | Lomefloxacin hydrochloride eye drops and preparation method and application thereof |
-
2014
- 2014-12-23 CN CN201410820214.3A patent/CN104491876A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1292752C (en) * | 1999-11-12 | 2007-01-03 | 贝林格尔·英格海姆国际有限公司 | Solutions containing epinastine |
| CN100998863A (en) * | 2006-01-12 | 2007-07-18 | 上海新药研究开发中心 | N-acetyl carnosine eye drops for preventing and treating cataract and its preparation method |
| CN102670493A (en) * | 2012-05-22 | 2012-09-19 | 宁夏康亚药业有限公司 | Lomefloxacin hydrochloride eye drops and preparation method and application thereof |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2020125318A (en) * | 2017-05-01 | 2020-08-20 | 参天製薬株式会社 | Eye drop |
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Application publication date: 20150408 |