CN103202833A - Pharmaceutical composition of olopatadine or salts of olopatadine, and preparation method thereof - Google Patents
Pharmaceutical composition of olopatadine or salts of olopatadine, and preparation method thereof Download PDFInfo
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- CN103202833A CN103202833A CN2012105676628A CN201210567662A CN103202833A CN 103202833 A CN103202833 A CN 103202833A CN 2012105676628 A CN2012105676628 A CN 2012105676628A CN 201210567662 A CN201210567662 A CN 201210567662A CN 103202833 A CN103202833 A CN 103202833A
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- olopatadine
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Abstract
The invention discloses a pharmaceutical composition of olopatadine or salts of olopatadine for treating allergic conjunctivitis, and a preparation method thereof. The composition mainly comprises the olopatadine or the salts of the olopatadine, and polycarbophil or polycarbophil salt or carbomer. The preparation method comprises firstly fully swelling the polycarbophil or the polycarbophil salt or the carbomer with a proper amount of pure water, and secondly adding the olopatadine or the salts of the olopatadine and other accessories.
Description
Technical field
The present invention relates to a kind of olopatadine of anaphylaxis conjunctivitis or Pharmaceutical composition of its salt and preparation method thereof of being used for the treatment of
Background technology
Being the doxepin derivant of representative with the olopatadine, is a kind of mast cell stabilizers with anti-histamine activity.Be used for prevention or treatment allergia oculopathy.Listing product Olopatadine hydrochloride eye drop, commodity are called Pa Tanluo, and its composition mainly is made up of olopatadine hydrochlorate, antibacterial, pH regulator agent, and using method is each 1～2 of trouble eye, every day 3～4 times, every medication in 6～8 hours once.Its side effect has headache, and is weak, and blurred vision is burnt or sensation of pricking, common cold syndrome, and eye is done, foreign body sensation, hyperemia, allergy, keratitis, blepharoedema is felt sick pharyngitis, pruritus, rhinitis, sinusitis and parageusia etc.As conventional sterile pure water solution eye drop, since the existence of cornea barrier, the reasons such as reversing of tear on the eyeball surface, and eye drop demonstrates lower bioavailability.Therefore, in order to keep normal local curative effect, the frequent drug administration of having to.This has caused two problems, the one, and conventional eye drop uses antiseptic and to the infringement of eye, the 2nd, the untoward reaction that the anti-histamine activity material produces.
Act on whole body for fear of antihistamine drug, minimizing is to the infringement of eye, and can make medicine stop prolongation at eye, continual release medicine is sought nontoxic nonirritant, can be become the key of dealing with problems by the pharmaceutically useful material of prolong drug in the eye holdup time to eye.
Summary of the invention
The object of the present invention is to provide and a kind ofly can prolong olopatadine or its salt slow release ophthalmic preparation in the holdup time of eye.This ophthalmic preparation mainly is made up of olopatadine or its salt and Polycarbophil or Polycarbophil salt or carbomer.The adhesive attraction of Polycarbophil and salt thereof or carbomer can improve medicine greatly in the anelasticity of eye, and under the effect of the slowly corrosion of tear and body temperature, slowly discharge medicine, not only can reduce administration number of times, the systemic side effects of medicine be can also avoid, thereby bioavailability of medicament and curative effect improved.
There is document to report for work, when carbomer is used for the scalp drug-supplying system of Progesterone, owing to be the unformed protein that is rich in sulfur around the skin keratin filament, the sulfhydrylation macromolecule can make total adhesion of medicine significantly greater than the control formulation made from PVP, HPMC by the exchange of disulfide bond, shown that the carbomer series polymer has unique biological adhesion (Pharm Res, 2001,18,211.).
People such as Ugwoke have carried out the bioavailability study of apomorphine mucosal adhesive drug delivery system rabbit nasal-cavity administration, make the powder formulation of medicine respectively with carbomer, Polycarbophil and lactose.Found that the above two f and MRT be obviously greater than the latter, and have the AUC value that equates with subcutaneous injection.Illustrate that the carbomer base polymer can be used for increasing the medicine holdup time by the bioadhesion at the nasal absorption position and reduce the removing (Eur J Pharm Sci, 1999,9,213.) of cilium.
People such as Bron find that under study for action 0.2% carbomer is compared with 1.4% polyvinyl alcohol, have similar safety, and the carbomer preparation can reduce dosing eyes number of times (Eur J Ophthalmol, 1998,8,81.).People such as Nagarsenker have prepared cation and the neutral fat plastid of tropicamide, and simultaneously the neutral fat plastid are dispersed in the gel of Polycarbophil and make neutral fat plastid gel, record pupil spread condition behind the rabbit dosing eyes.Relatively mydriasis intensity through the time curve show that tmax is significantly greater than the aqueous solution of medicine behind the neutral fat plastid gel delivery; Behind the gel delivery of simple medicine AUC and cationic-liposome and neutral fat plastid gel phase with, the true cause of this presentation of results AUC increase be the viscosity of Polycarbophil but not liposome medicine (Int J Pharm, 1999,190,63.).
In sum, carbomer and Polycarbophil are used for skin, mucosa, ocular drug transmission system, it is little to have zest, and the surface detention time is long, improves characteristics such as bioavailability of medicament, can be used as the substrate of gel and Emulsion.
Based on above result of study, in order to prolong Olopatadine hydrochloride in the holdup time of eye, can utilize acrylate copolymer carbomer or Polycarbophil and salt thereof to prepare the Pharmaceutical composition of a usefulness.
A kind of olopatadine of anaphylaxis conjunctivitis or Pharmaceutical composition of its salt of being used for the treatment of provided by the invention is characterized in that said composition mainly contains olopatadine or its salt, Polycarbophil or Polycarbophil salt or carbomer.Contain 0.1% olopatadine or Polycarbophil or Polycarbophil salt or the carbomer of its salt (content calculates with olopatadine) and 0.02～2% (w/v) in the said composition.The salt of the olopatadine that contains in the said composition refers to hydrochlorate.Said composition contains the antioxidant that can stablize Polycarbophil or Polycarbophil salt or carbomer, and antioxidant is selected from disodium edetate, sodium thiosulfate or sodium citrate, preferred disodium edetate.The content of disodium edetate is 0.005～0.05% in the said composition.
The preparation method of the Pharmaceutical composition of a kind of olopatadine that is used for the treatment of anaphylaxis conjunctivitis provided by the invention or its salt, it is characterized in that at first using an amount of pure water with Polycarbophil or Polycarbophil salt or the abundant swelling of carbomer, add olopatadine or its salt and other adjuvants again.
The specific embodiment
Following exemplary embodiments is used for illustrating the present invention, all belongs within the technical scheme that the present invention protects in simple replacement that those skilled in the art do the present invention or improvement etc.
Embodiment 1:
Preparation prescription of the present invention is composed of the following components:
Preparation technology:
1) under aseptic condition, carbomer and an amount of water for injection are fully got solution 1 after the swelling at ambient temperature;
2) with Olopatadine hydrochloride, benzalkonium chloride respectively with after the dissolving of an amount of water for injection, merge solution 2;
3) mannitol, sodium chloride, disodium edetate, poloxamer are dissolved in the proper amount of water for injection successively, get solution 3;
4) under aseptic condition, solution 1, solution 2, solution 3 are merged, by high speed dispersing emulsification machine mix homogeneously, with 1M sodium hydroxide solution adjust pH to 5～7, add the injection water again to total amount;
5) after the sterilization, be cooled to room temperature, divide under the aseptic condition to be filled to sterilized eye drop bottle.
Embodiment 2:
Preparation prescription of the present invention is composed of the following components:
Preparation technology:
1) under aseptic condition, Polycarbophil and an amount of water for injection at ambient temperature fully after the swelling, are got solution 1;
2) with Olopatadine hydrochloride, benzalkonium bromide respectively with after the dissolving of an amount of water for injection, merge solution 2;
3) mannitol, sodium chloride, disodium edetate, polyoxyethylene sorbitan monoleate are dissolved in the proper amount of water for injection successively, get solution 3;
4) under aseptic condition, solution 1, solution 2, solution 3 are merged, by high speed dispersing emulsification machine mix homogeneously, with 1M sodium hydroxide solution adjust pH to 5～7, add the injection water again to total amount;
5) after the sterilization, be cooled to room temperature, divide under the aseptic condition to be filled to sterilized eye drop bottle.
Embodiment 3: the experiment of rabbit eye holdup time
Purpose: the length of eye holdup time is to weigh eye with an important indicator of sustained-release eye drop, and for investigating between this product and the commercial eye drops product difference in the eye holdup time, employing fluorescein method compared the two lagophthalmos portion holdup time of being in.
The preparation of test sample: in embodiment 1 and embodiment 2 prepared products and commercially available Pa Tanluo (Olopatadine hydrochloride eye drop, Alcon Universal Ltd.), add 0.05% fluorescein sodium respectively.
Method: select 18 of healthy rabbits for use, be divided into three groups, with the rabbit fixing head, mention palpebra inferior, conjunctival sac is pulled into ring-type, in the conjunctival sac of three groups of rabbit left eyes, splash into embodiment 1 product that contains fluorescein sodium, embodiment 2 products and commercially available each 20 μ L of Pa Tanluo respectively, splash into the Pa Tanluo that 20 μ L contain fluorescein sodium and organize in contrast.After the administration, make the passive closed 10s of rabbit eyes, be placed in the rabbit folder and use slit lamp observation, observe fluorescence coating power in rabbit cornea surface and the conjunctival sac at regular intervals.The time that conjunctival sac inner surface continuous fluorescence layer is disappeared is decided to be the eye holdup time.Experimental result is seen shown in the form in the accompanying drawing 1.
Analyze: find in the observation that Pa Tanluo is difficult to stop at rabbit cornea, part flows out from the canthus, and the product of embodiment 1 and embodiment 2 is uniformly distributed on conjunctiva and the cornea after splashing in the conjunctival sac.Compare with matched group, the product of embodiment 1 and embodiment 2 has increased by 2～3 times in the eye holdup time, shows to have good eye retention effect by the prepared Pharmaceutical composition that contains olopatadine of the present invention, the results are shown in accompanying drawing 2.
Description of drawings
Fig. 1 is the rabbit eye holdup time data of 2 groups of 1 group of embodiment, embodiment and Pa Tanluo matched group; Fig. 2 is the rabbit eye holdup time bar diagram according to 2 groups of 1 group of embodiment, embodiment and Pa Tanluo matched group.
Claims (8)
1. one kind is used for the treatment of the olopatadine of anaphylaxis conjunctivitis or the Pharmaceutical composition of its salt, it is characterized in that said composition mainly contains olopatadine or its salt, Polycarbophil or Polycarbophil salt or carbomer.
2. Pharmaceutical composition according to claim 1 is characterized in that said composition contains 0.1% olopatadine or its salt (content calculates with olopatadine).
3. according to claim 1 and 2 described Pharmaceutical compositions, it is characterized in that the salt that said composition contains olopatadine is hydrochlorate.
4. Pharmaceutical composition according to claim 1 is characterized in that said composition contains Polycarbophil or Polycarbophil salt or the carbomer of 0.02～2% (w/v).
5. Pharmaceutical composition according to claim 1 is characterized in that said composition contains the antioxidant that can stablize Polycarbophil or Polycarbophil salt or carbomer.
6. according to claim 1 and 5 described Pharmaceutical compositions, it is characterized in that the antioxidant that said composition contains is selected from disodium edetate, sodium thiosulfate or sodium citrate, preferred disodium edetate.
7. according to claim 1,5 and 6 described Pharmaceutical compositions, it is characterized in that said composition contains 0.005～0.05% disodium edetate.
8. the preparation method of the described Pharmaceutical composition of claim 1 is characterized in that at first using an amount of pure water with Polycarbophil or Polycarbophil salt or the abundant swelling of carbomer, adds olopatadine or its salt and other adjuvants again.
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| Application Number | Priority Date | Filing Date | Title |
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| CN2012105676628A CN103202833A (en) | 2012-12-25 | 2012-12-25 | Pharmaceutical composition of olopatadine or salts of olopatadine, and preparation method thereof |
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| Application Number | Priority Date | Filing Date | Title |
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| CN2012105676628A CN103202833A (en) | 2012-12-25 | 2012-12-25 | Pharmaceutical composition of olopatadine or salts of olopatadine, and preparation method thereof |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115887367A (en) * | 2022-11-21 | 2023-04-04 | 山东诺明康药物研究院有限公司 | Olopatadine hydrochloride in-situ gel eye drops and preparation method and application thereof |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1161000A (en) * | 1995-06-06 | 1997-10-01 | 阿尔康实验室公司 | Topical ophthalmic formulations containing Doxepin derivatives for treating allergic eye diseases |
| CN101641094A (en) * | 2007-04-11 | 2010-02-03 | 爱尔康研究有限公司 | Use of an inhibitor of tnfa plus an antihistamine to treat allergic rhinitis and allergic conjunctivitis |
| CN101966144A (en) * | 2009-07-28 | 2011-02-09 | 胡容峰 | Preparation and application of olopatadine in-situ gel |
| CN102548536A (en) * | 2009-10-01 | 2012-07-04 | 爱尔康研究有限公司 | Olopatadine compositions and uses thereof |
-
2012
- 2012-12-25 CN CN2012105676628A patent/CN103202833A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1161000A (en) * | 1995-06-06 | 1997-10-01 | 阿尔康实验室公司 | Topical ophthalmic formulations containing Doxepin derivatives for treating allergic eye diseases |
| CN101641094A (en) * | 2007-04-11 | 2010-02-03 | 爱尔康研究有限公司 | Use of an inhibitor of tnfa plus an antihistamine to treat allergic rhinitis and allergic conjunctivitis |
| CN101966144A (en) * | 2009-07-28 | 2011-02-09 | 胡容峰 | Preparation and application of olopatadine in-situ gel |
| CN102548536A (en) * | 2009-10-01 | 2012-07-04 | 爱尔康研究有限公司 | Olopatadine compositions and uses thereof |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115887367A (en) * | 2022-11-21 | 2023-04-04 | 山东诺明康药物研究院有限公司 | Olopatadine hydrochloride in-situ gel eye drops and preparation method and application thereof |
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Effective date of registration: 20170825 Address after: 224600 economic development zone of Xiangshui County, Jiangsu, Yancheng City Applicant after: Jiangsu Yabang Aipusen Pharmaceutical Co., Ltd. Address before: 213163 No. 105 Renmin West Road, Wujin District, Jiangsu, Changzhou Applicant before: Changzhou Yabang Pharmaceutical & Chemical Co., Ltd. Applicant before: Yabang Pharmaceutical Co., Ltd. Applicant before: Jiangsu Yabang Aipusen Pharmaceutical Co., Ltd. |
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