CN109125318B

CN109125318B - Application of butylphthalide in preparation of medicine for treating xerophthalmia

Info

Publication number: CN109125318B
Application number: CN201810659271.6A
Authority: CN
Inventors: 孙勇军; 吕晓倩; 陈玺; 彭姣; 候丽蓓; 陈若莹; 张福云; 李晨晨; 赵凯; 高子彬
Original assignee: Hebei University of Science and Technology
Current assignee: Hebei University of Science and Technology
Priority date: 2018-06-25
Filing date: 2018-06-25
Publication date: 2020-11-17
Anticipated expiration: 2038-06-25
Also published as: CN109125318A

Abstract

The invention provides a new medical application of butylphthalide, and relates to an application of butylphthalide in preparing a medicine for treating xerophthalmia.

Description

Application of butylphthalide in preparation of medicine for treating xerophthalmia

Technical Field

The invention belongs to the field of medicines, relates to a medical application of a compound butylphthalide, and particularly relates to an application of the compound butylphthalide as an active ingredient in preparation of a medicine for treating xerophthalmia.

Background

Dry eye refers to a general term for a variety of diseases characterized by abnormal quality or quantity of tear fluid or abnormal kinetics of any cause, resulting in decreased tear film stability, and ocular discomfort and/or ocular surface tissue pathology, which can cause keratoconjunctival disorders and affect vision. With the widespread use of computers and smart phones in recent years, the eye-use time of people is continuously increased, and the incidence of xerophthalmia is obviously increased due to the influence of poor eye-use habits. Dry eye has become a global epidemic disease, and the incidence of dry eye in our country is gradually increasing and the trend is towards youthful. Research shows that the inflammatory reaction of ocular surface tissues is the main cause of the reduction of tear secretion in xerophthalmia, and the prior treatment of xerophthalmia mainly comprises artificial tears, corticosteroid hormones, and immunosuppressive agents such as cyclosporine A. Wherein, the artificial tears are only a substitute of tears, and have no treatment effect; the medicines such as corticosteroid hormone and cyclosporine A have certain toxic and side effects on the ocular surface after long-term use. Therefore, a medicine which has good effect and no obvious local and systemic toxic and side effects after long-term use is urgently needed in clinic.

Butylphthalide (NBP) is a water-insoluble oily substance with strong celery flavor, is racemate extracted from semen Apii Graveolentis, and can also be synthesized by artificial method with chemical formula C₁₂H₁₄O₂The relative molecular weight is 190.24, and the chemical structure is as follows:

the medicine is clinically used for treating mild and moderate acute ischemic cerebral apoplexy by oral administration or injection administration. In recent years, a large number of domestic and foreign research reports show that the butylphthalide has various pharmacological effects, and the treatment field relates to the aspects of central nervous system, cardiovascular system, diabetic complication, hypertension and the like. At present, no relevant report research on the application of butylphthalide in the alleviation of xerophthalmia and preparations thereof exists, the invention provides the application of butylphthalide in the preparation of xerophthalmia treatment medicines, provides a new idea for xerophthalmia treatment, and provides a new field for development and application of butylphthalide.

Disclosure of Invention

In order to solve the problems in the background art, experimental research shows that butylphthalide can improve the tear secretion of mice, prolong the tear film rupture time and show good application prospects for prevention and treatment of xerophthalmia.

Therefore, the invention provides the application of butylphthalide in preparing a medicine for treating dry eye, wherein the effective component of the medicine for treating dry eye is butylphthalide, and the medicine also comprises pharmaceutically acceptable auxiliary materials.

The medicine for treating xerophthalmia is prepared into acceptable eye drops.

The pharmaceutically acceptable auxiliary materials comprise one or more of tween 80, polyoxyethylene castor oil, polyethylene glycol 15 hydroxystearate, beta-cyclodextrin, methyl-beta-cyclodextrin, hydroxypropyl-beta-cyclodextrin, gamma-cyclodextrin, hydroxypropyl-gamma-cyclodextrin, benzalkonium bromide, benzalkonium chloride, sodium chloride, glucose, phosphate buffer and boric acid buffer.

The dosage range of the medicine butylphthalide for treating xerophthalmia is 0.2-0.6%.

Drawings

FIG. 1 shows the results of observation of corneal fluorescein sodium staining in mice (left: control group; right: administration group).

Detailed Description

The present invention will be described in detail with reference to the following embodiments.

Example 1

Adding the polyoxyethylene castor oil, the sodium chloride and the benzalkonium chloride in the prescription amount into 80g of hot water for injection, and stirring until the polyoxyethylene castor oil, the sodium chloride and the benzalkonium chloride are dissolved; adding butylphthalide into the solution, stirring to dissolve, and adding water to total amount of 100 g. Filtering, sterilizing under hot pressure for 15min, and packaging to obtain butylphthalide eye drop.

Example 2

Adding polyethylene glycol 15 hydroxystearate, sodium chloride and benzalkonium chloride in a prescribed amount into 80g of hot water for injection, and stirring until the mixture is dissolved; adding butylphthalide into the solution, stirring to dissolve, and adding water to total amount of 100 g. Filtering, sterilizing under hot pressure for 15min, and packaging to obtain butylphthalide eye drop.

Example 3

Adding the gamma-cyclodextrin, the sodium chloride and the benzalkonium chloride in the prescription amount into 80g of hot water for injection, and stirring until the gamma-cyclodextrin, the sodium chloride and the benzalkonium chloride are dissolved; butylphthalide is added into the solution, stirred until the solution is oilless, and water is added until the total amount is 100 g. Sterilizing under hot pressure for 15min, and packaging to obtain butylphthalide eye drop.

Example 4

Adding the prescribed amount of methyl-beta-cyclodextrin, sodium chloride and benzalkonium chloride into 80g of hot water for injection, and stirring until the mixture is dissolved; adding butylphthalide into the solution, stirring to dissolve, and adding water to total amount of 100 g. Filtering, sterilizing under hot pressure for 15min, and packaging to obtain butylphthalide eye drop.

Example 5

Adding the hydroxypropyl-beta-cyclodextrin, sodium chloride and benzalkonium chloride in the prescribed amount into 80g of hot water for injection, and stirring until the mixture is dissolved; adding butylphthalide into the solution, stirring to dissolve, and adding water to total amount of 100 g. Filtering, sterilizing under hot pressure for 15min, and packaging to obtain butylphthalide eye drop.

Example 6: study of pharmacodynamics

Establishment of xerophthalmia animal model

Healthy male BALB/c mice 60, 8 weeks old, body mass (20. + -.3 g), were administered 0.2% (w/w) benzalkonium chloride aqueous solution as eye drops, 2 times daily for 14 days.

Measurement of tear secretion and tear film rupture time

The lacrimal secretion is measured by a test paper method, namely the test paper is placed in the lower eyelid of the mouse for 30 seconds, and the weight increment of the test paper is weighed as the measurement result of the lacrimal secretion.

The tear film rupture time is measured by adopting a fluorescence method, the mouse conjunctival sac is stained by 0.125 percent fluorescein sodium, the eye is manually performed for 3 times, then the eye is irradiated by cobalt blue light, and the observation is carried out by a slit lamp microscope. The tear film rupture time is determined by the time the eye is in the transient state until the black or linear defect appears in the tear film of the mouse.

Dosage regimen

40 dry eye mice with similar tear secretion and tear film rupture time are taken and randomly divided into 2 groups: control group and administration group. The eye part is continuously dosed for 14 days 3 times a day, a blank solution without butylphthalide is dosed to a control group, and butylphthalide eye drops are dosed to a dosing group. The tear secretions and tear film break-up time were again measured in groups 2 of mice after 14 days.

4. results

After the benzalkonium chloride is adopted to induce the mice to generate xerophthalmia, the mice receiving the butylphthalide eye drops are remarkably increased in tear secretion amount and prolonged in tear film rupture time compared with the control group of mice.

Claims

1. The application of butylphthalide in preparing medicine for treating xerophthalmia.

2. The use according to claim 1, wherein said butylphthalide is used as an active ingredient in the preparation of a pharmaceutical composition for the treatment of dry eye.

3. The use according to claim 1, wherein said butylphthalide is used in combination with a pharmaceutically acceptable excipient in the manufacture of a medicament for the treatment of dry eye.

4. The use of claim 3, wherein said butylphthalide is formulated as eye drops with pharmaceutically acceptable excipients.

5. The use of claim 4, wherein the pharmaceutically acceptable excipients comprise one or more of Tween 80, polyoxyethylene castor oil, polyethylene glycol 15 hydroxystearate, beta-cyclodextrin, methyl-beta-cyclodextrin, hydroxypropyl-beta-cyclodextrin, gamma-cyclodextrin, hydroxypropyl-gamma-cyclodextrin, benzalkonium bromide, benzalkonium chloride, sodium chloride, glucose, phosphate buffer, and boric acid buffer.

6. The use according to claim 1, wherein the concentration of butylphthalide is in the range of 0.01% to 1%.

7. The use according to claim 6, wherein the concentration of butylphthalide is in the range of 0.2% to 0.6%.