CN109125318A - Application of the butylphenyl phthaleine in preparation treatment dry eye drugs - Google Patents
Application of the butylphenyl phthaleine in preparation treatment dry eye drugs Download PDFInfo
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- CN109125318A CN109125318A CN201810659271.6A CN201810659271A CN109125318A CN 109125318 A CN109125318 A CN 109125318A CN 201810659271 A CN201810659271 A CN 201810659271A CN 109125318 A CN109125318 A CN 109125318A
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- Prior art keywords
- butylphenyl phthaleine
- cyclodextrin
- preparation treatment
- application according
- application
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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
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/365—Lactones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/04—Artificial tears; Irrigation solutions
Abstract
The present invention provides a kind of medical usages that butylphenyl phthaleine is new, are related to application of the butylphenyl phthaleine in preparation treatment dry eye drugs.
Description
Technical field
The invention belongs to field of medicaments, are related to the medical usage more particularly to a kind of compound of a kind of compound butylphenyl phthaleine
Application of the butylphenyl phthaleine as active constituent in preparation treatment dry eye drugs.
Background technique
Xerophthalmia refers to that tear matter caused by any reason or amount exception or dynamics are abnormal, causes under tear film stability
Drop, and with ophthalmic uncomfortable and (or) the general name of a variety of diseases of ocular lesion tissue feature, angle conjunctive disorder, and meeting can be caused
It affects vision.Be widely used recently as computer, smart phone, people with constantly increasing between at the moment, bad use in addition
The influence of eye habit, causes xerophthalmia disease incidence obviously to rise.Xerophthalmia has become global pandemic disease, China's xerophthalmia
Disease incidence gradually rises and has the tendency that rejuvenation.Studies have shown that the inflammatory reaction of ocular tissue is lacrimal secretion in xerophthalmia
The main inducing of reduction, the treatment of xerophthalmia is mainly exempted from artificial tears, corticosteroid hormone and Ciclosporin A etc. at present
Based on epidemic disease inhibitor.Wherein, artificial tears are only a kind of tear substitutes, itself is without therapeutic effect；Corticosteroid hormone
And the long-time service of the drugs such as Ciclosporin A has certain toxic side effect to ocular.Therefore, clinically need a kind of effect it is good and
The drug without obvious part and whole body toxic side effect is used for a long time.
Butylphenyl phthaleine (Butylphthalide, NBP) is a kind of oily matter not soluble in water, has strong celery taste,
It is the raceme extracted from celery seed, can also be artificial synthesized, chemical formula C12H14O2, relative molecular weight 190.24,
Its chemical structure is as follows:
Clinically by oral or injection administration for treating light, moderate acute ischemic cerebral apoplexy.In recent years, a large amount of both at home and abroad
Research report shows a variety of pharmacotoxicological effects of butylphenyl phthaleine, and therapy field is related to central nervous system, cardiovascular system, diabetes
Complication, hypertension etc..It is applied to alleviate the relevant report research of xerophthalmia and its preparation there is presently no butylphenyl phthaleine, this
Invention provides application of the butylphenyl phthaleine in preparation treatment dry eye drugs, provides new approaches for the treatment of xerophthalmia, is fourth
The development and application of phthalide provide frontier.
Summary of the invention
To solve the problems in the background art, by experimental studies have found that, butylphenyl phthaleine can improve the tear of mouse
Secretion extends breakup time of tear film, shows good application prospect for the prevention and treatment of xerophthalmia.
For this purpose, the application the present invention provides butylphenyl phthaleine in preparation treatment dry eye drugs, the treatment xerophthalmia medicine
Object effective component is butylphenyl phthaleine, further includes pharmaceutically acceptable auxiliary material.
Acceptable eye drops is made in the treatment dry eye drugs.
The pharmaceutically acceptable auxiliary material includes Tween 80, Emulsifier EL-60,15 hydroxy stearic acid of polyethylene glycol
Ester, beta-cyclodextrin, methyl-B-cyclodextrin, hydroxypropyl-β-cyclodextrin, gamma-cyclodextrin, hydropropyl-y-cyclodextrin, benzene prick bromine
One of ammonium, benzalkonium chloride, sodium chloride, glucose, phosphate buffer, borate buffer are any several.
The dosage range of the treatment dry eye drugs butylphenyl phthaleine is 0.2-0.6%.
Detailed description of the invention
Fig. 1 mouse cornea fluorescein sodium dyeing observation result is (left: control group；It is right: administration group).
Specific embodiment
The present invention is described in detail With reference to embodiment.
Embodiment 1
The Emulsifier EL-60, sodium chloride and benzalkonium chloride of recipe quantity is taken to be added in the hot water for injection of 80g, stirring to dissolution；
Butylphenyl phthaleine is added into above-mentioned solution, stirring adds water to total amount 100g to dissolving.Filtering, pressure sterilizing 15min, packing obtain fourth
Phthalide eye drops.
Embodiment 2
The Solutol HS 15, sodium chloride and benzalkonium chloride of recipe quantity is taken to be added in the hot water for injection of 80g, stirring
To dissolution；Butylphenyl phthaleine is added into above-mentioned solution, stirring adds water to total amount 100g to dissolving.Filtering, pressure sterilizing 15min, point
Dress, obtains butylphenyl phthaleine eye drops.
Embodiment 3
The gamma-cyclodextrin, sodium chloride and benzalkonium chloride of recipe quantity is taken to be added in the hot water for injection of 80g, stirring to dissolution；To above-mentioned
Butylphenyl phthaleine is added in solution, stirs to no grease, adds water to total amount 100g.Pressure sterilizing 15min, packing obtain butylphenyl phthaleine drop
Ocular fluid.
Embodiment 4
The methyl-B-cyclodextrin, sodium chloride and benzalkonium chloride of recipe quantity is taken to be added in the hot water for injection of 80g, stirring to dissolution；To
Butylphenyl phthaleine is added in above-mentioned solution, stirring adds water to total amount 100g to dissolving.Filtering, pressure sterilizing 15min, packing obtain butylbenzene
Phthalein eye drops.
Embodiment 5
Hydroxypropyl-β-cyclodextrin, sodium chloride and the benzalkonium chloride of recipe quantity is taken to be added in the hot water for injection of 80g, stirring to dissolution；
Butylphenyl phthaleine is added into above-mentioned solution, stirring adds water to total amount 100g to dissolving.Filtering, pressure sterilizing 15min, packing obtain fourth
Phthalide eye drops.
Embodiment 6: pharmacodynamic study
1, xerophthalmia Animal Model
Healthy male BALB/c mouse 60,8 week old, weight (20 ± 3) g give 0.2% (w/w) benzalkonium chloride in water
Eye drip is administered daily 2 times, and successive administration 14 days.
The measurement of 2, lacrimal secretion objects and breakup time of tear film
Lacrimal secretion object is measured using test paper method, i.e., is placed in test paper in mouse lower eyelid 30 seconds, is weighed test paper weight gain and is made
For the measurement result of lacrimal secretion.
Breakup time of tear film uses fluorescence spectrometry, 0.125% fluorescein sodium of mouse conjunctival sac dyeing, after twinkling manually 3 times
With cobalt blue light illumination, slit lamp microscope observation.It finishes mouse tear film to twinkle and black or linear defect occurs as tear film
Rupture time.
3, dosage regimens
Lacrimal secretion and close xerophthalmia mouse 40 of breakup time of tear film are taken, is randomly divided into 2 groups: control group and administration
Group.3 times a day, continuous ophthalmic administration 14 days, control group give the blank solution without butylphenyl phthaleine, and administration group gives butylphenyl phthaleine drop
Eye agent.2 groups of mouse measure lacrimal secretion object and breakup time of tear film again after 14 days.
4, results
After xerophthalmia occurs using benzalkonium chloride inducing mouse, the mouse for receiving the treatment of butylphenyl phthaleine eye drops is small relative to control group
Mouse, lacrimal secretion dramatically increases, breakup time of tear film extends.
Claims (7)
1. application of the butylphenyl phthaleine in the drug of preparation treatment xerophthalmia.
2. application according to claim 1, which is characterized in that medicine group of the butylphenyl phthaleine as preparation treatment xerophthalmia
Close active component when object.
3. application according to claim 1, which is characterized in that the butylphenyl phthaleine preparation treatment dry eye drugs in medicine
Acceptable auxiliary material is used in combination on.
4. the application according to claim 3, which is characterized in that prepared by the butylphenyl phthaleine and pharmaceutically acceptable auxiliary material
At eye drops.
5. the application according to claim 4, which is characterized in that the pharmaceutically acceptable auxiliary material include Tween 80,
Emulsifier EL-60, Solutol HS 15, beta-cyclodextrin, methyl-B-cyclodextrin, hydroxypropyl-β-cyclodextrin,
Gamma-cyclodextrin, hydropropyl-y-cyclodextrin, benzalkonium bromide, benzalkonium chloride, sodium chloride, glucose, phosphate buffer, boric acid
One of buffer is any several.
6. the application according to claim 1, which is characterized in that the concentration range of the butylphenyl phthaleine is 0.01%-1%.
7. the application according to claim 6, which is characterized in that the concentration range of the butylphenyl phthaleine is 0.2%-0.6%.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810659271.6A CN109125318B (en) | 2018-06-25 | 2018-06-25 | Application of butylphthalide in preparation of medicine for treating xerophthalmia |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810659271.6A CN109125318B (en) | 2018-06-25 | 2018-06-25 | Application of butylphthalide in preparation of medicine for treating xerophthalmia |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN109125318A true CN109125318A (en) | 2019-01-04 |
| CN109125318B CN109125318B (en) | 2020-11-17 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201810659271.6A Expired - Fee Related CN109125318B (en) | 2018-06-25 | 2018-06-25 | Application of butylphthalide in preparation of medicine for treating xerophthalmia |
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| Country | Link |
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| CN (1) | CN109125318B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110859835A (en) * | 2019-12-23 | 2020-03-06 | 河北科技大学 | Application of butylphthalide in preparation of medicine for treating corneal injury |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7482027B2 (en) * | 2005-04-30 | 2009-01-27 | Angiolab, Inc. | Composition for the prevention or treatment of diseases associated with angiogenesis |
| CN102451177A (en) * | 2010-10-22 | 2012-05-16 | 石药集团恩必普药业有限公司 | Application of butylphthalide or derivatives thereof in preparation of medicaments for promoting angiogenesis |
| CN104546828A (en) * | 2013-10-09 | 2015-04-29 | 石药集团恩必普药业有限公司 | Application of butylphthalide or derivative in preparation of medicine for treating or preventing diabetic complication |
| KR20180059101A (en) * | 2016-11-25 | 2018-06-04 | 오좌섭 | Anti-allergic composition and composition for improving atopic dermatitis using 5-hydroxy-6,7-dimethoxyphthalide |
-
2018
- 2018-06-25 CN CN201810659271.6A patent/CN109125318B/en not_active Expired - Fee Related
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7482027B2 (en) * | 2005-04-30 | 2009-01-27 | Angiolab, Inc. | Composition for the prevention or treatment of diseases associated with angiogenesis |
| CN102451177A (en) * | 2010-10-22 | 2012-05-16 | 石药集团恩必普药业有限公司 | Application of butylphthalide or derivatives thereof in preparation of medicaments for promoting angiogenesis |
| CN104546828A (en) * | 2013-10-09 | 2015-04-29 | 石药集团恩必普药业有限公司 | Application of butylphthalide or derivative in preparation of medicine for treating or preventing diabetic complication |
| KR20180059101A (en) * | 2016-11-25 | 2018-06-04 | 오좌섭 | Anti-allergic composition and composition for improving atopic dermatitis using 5-hydroxy-6,7-dimethoxyphthalide |
Non-Patent Citations (4)
| Title |
|---|
| WAN CHEN ET AL.: "Microvascular abnormalities in dry eye patients", 《MICROVASCULAR RESEARCH》 * |
| 左晶等: "丁苯酞治疗早期前部缺血性视神经病变的疗效观察", 《中国中医眼科杂志》 * |
| 杜军辉等: "眼科应用复方血栓通的临床进展", 《中华临床医师杂志(电子版)》 * |
| 陶剑虹: "国内外改善微循环障碍药物分析", 《中国处方药》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110859835A (en) * | 2019-12-23 | 2020-03-06 | 河北科技大学 | Application of butylphthalide in preparation of medicine for treating corneal injury |
| CN110859835B (en) * | 2019-12-23 | 2022-11-11 | 河北科技大学 | Application of butylphthalide in preparation of medicine for treating corneal injury |
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| Publication number | Publication date |
|---|---|
| CN109125318B (en) | 2020-11-17 |
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