CN107714709B - Use of aescin and its salt in preparing medicine for treating cataract - Google Patents

Abstract

The invention discloses an application of aescin and its salt in preparing medicine for treating cataract, belonging to the field of pharmacy. The treatment effect of the aescin and the salt thereof on the rat cataract is evaluated by injecting a galactose rat cataract model and adopting a lens opacity grading method, and the result shows that the aescin and the salt thereof can obviously reduce the opacity grade of the lens, thereby verifying that the aescin and the salt thereof have the effect of delaying the formation and development of the rat cataract.

Description

Use of aescin and its salt in preparing medicine for treating cataract

Technical Field

The invention relates to a new pharmaceutical application of aescin and salts thereof, in particular to a new application in preparing a medicine for treating cataract, and the invention also relates to eye drops for treating cataract, belonging to the pharmaceutical field.

Background

Cataract is a common ophthalmic disease and is an important factor causing blindness. At present, with the increasing aging of the population in China, the incidence of cataract is also increased remarkably. The occurrence of cataract can be caused by aging, heredity, immunity, metabolic abnormality, radiation, poisoning, trauma, and local nutrition, and the most important physicochemical process of cataract is lenticular opacity through the formation of protein polymers. Because the mechanism of cataract formation is quite complex, it is currently believed that the phenomena of aggregation and syneresis can lead to lenticular opacity, and therefore surgical treatment is required for such patients, but for incipient cataracts, patients who do not require surgery or who are unwilling to undergo surgery are often treated only with drug conservation.

Modern medicine's theory of local treatment of cataract is based on the theory of malnutrition, quinones and oxidation, and the like, and the role of, for example, pirenoxine sodium (hydantoin) is to competitively inhibit the action of quinones on the soluble proteins of the lens, thereby counteracting damage of free radicals to the lens.

Aescin, also called aescin acid, is the general name of total saponin, beta-aescin or isoaescin extracted from seeds of aesculus plant of aesculaceae, and belongs to triterpenoid saponin. Aescin is poorly water soluble and is often made into salts in order to increase its solubility. The aescin and its salt are used clinically in treating various kinds of cerebral edema, accompanying cerebral dysfunction, various kinds of inflammation and swelling caused by wound, burn, operation, etc. and have powerful antiphlogistic and antiseepatic functions and capacity of reducing acute inflammatory exudation.

CN 102920722 a discloses an ophthalmic preparation containing 0.05-0.5% sodium aescinate, which can be used for treating fundus diseases such as central serous chorioretinopathy, fundus hemorrhage, eyeball blunt contusion, optic nerve injury, etc. However, the part of cataract is the crystalline lens, and the cornea, iris and crystalline lens in front of the eyeball are already defined as anterior segment of eye by ophthalmology, which obviously does not belong to the category of fundus diseases. In addition, the pathogenesis of cataract is more complicated than that of eyeground disease, and the treatment means is also obviously different from the eyeground disease (such as cataract), which is the reason that no medicine capable of completely curing cataract exists so far. Therefore, the person skilled in the art cannot think that the sodium aescinate can also treat cataract on the basis of CN 102920722A, and other aescinates and salts thereof for treating cataract have not been reported so far.

Disclosure of Invention

The first purpose of the invention is to provide the use of aescin and its salt in preparing medicine for treating cataract, and the second purpose of the invention is to provide eye drops for treating cataract.

The invention evaluates the treatment effect of the lysine aescin eye drops on rat cataract by injecting galactose into a rat cataract model and adopting a lens opacity grading method, and the result shows that the lysine aescin eye drops can obviously reduce the opacity grade of the lens, thereby verifying that the aescin and the salt thereof have the function of delaying the formation and development of rat cataract.

The eye drops for treating cataract provided by the invention contain aescin and salts thereof, wherein the weight content of the aescin and the salts thereof is 0.5-1.5% (the aescin salts are the content of the aescin in a conversion way).

Most preferably, the content of escin and its salt is 0.8% by weight (i.e. the medium dose in example 1).

The aescin and its salt as referred in the present invention refers to free aescin or its salt, preferably lysine aescin, when it is aescin salt, but also other forms of medicinal salts such as sodium or potassium aescin salt.

The eye drops also comprise auxiliary materials used for preparation, such as osmotic pressure regulator, buffer, stabilizer, preservative, cosolvent, viscosity regulator and the like. The person skilled in the art can refer to pharmacy and other literature in preparing the eye drops of the present invention, optionally using the above-mentioned adjuvants and using conventional amounts and methods without overcoming technical obstacles.

The osmotic pressure regulator includes saccharides such as sucrose, glucose, sorbitol, mannitol, etc.; polyhydric alcohols such as glycerin, propylene glycol, and the like; salts such as sodium chloride, potassium chloride, and the like; and boric acid for adjusting osmotic pressure of the eye drops to be isotonic with human tears.

The buffering agent includes borate, phosphate, citrate, acetate, etc., and functions to adjust the pH of the ophthalmic solution to a range tolerable to the human eye, e.g., between 5 and 9.

The stabilizer comprises EDTA-2Na and the like.

The cosolvent comprises nonionic surfactant such as tween, span and the like.

The viscosity regulator comprises water soluble polymer or cellulose, such as polyvinylpyrrolidone, polyethylene glycol, carbomer, methylcellulose, hydroxyethyl cellulose, sodium carboxymethylcellulose, etc., and is used for increasing viscosity of eye drop and prolonging retention time in eye.

The preservatives include quaternary ammonium salts, parabens, benzyl alcohol, sorbic acid, chlorobutanol, and the like.

The eye drops provided by the invention not only have obvious curative effect on cataract, but also have small irritation to eyes and good safety.

Detailed Description

The present invention will be described in detail below with reference to examples.

EXAMPLE 1 efficacy test of aescine and its salts for cataract

Test drugs: 50% D-galactose solution, BAINENGTING eye drop (0.05mg/ml), and lysine aescin eye drop (0.5%, 0.8%, 1.2%).

120 young mice of 3 weeks old are taken, and the male and female mice are divided into 6 groups randomly, wherein each group comprises 20 mice: blank group, model group, positive control group, lysine aescin high, medium and low dose group. Observing with a slit microscope before administration, wherein the crystal is transparent for use; molding: animals were injected with 50% D-galactose solution 15g/kg intraperitoneally twice a day, with an interval of 4 hours or more, continuously for 14 days, and the animals in the blank group were dropped into both eyes with normal saline (0.1 mL/eye). The model group is given with 1 drop/eye of physiological saline, the positive control group is given with 1 drop/eye of the BAINING eye drops, the high, middle and low dosage groups of the lysine aescin are respectively given with 1 drop/eye of the lysine aescin eye drops of 1.2%, 0.8% and 0.5%, the dosage is given three times per day for 3 weeks continuously, the last day is observed with 1% atropine mydriasis, after ether anesthesia, the rat lens is observed with a slit lamp microscope, the time of the occurrence of the lenticular opacity is recorded and graded. Specific grading criteria for the degree of lenticular opacity are as follows: i indicates no turbidity, and the crystalline lens is transparent and clear; II indicates nuclear cloudiness, i.e. crystalline cloudiness, but clear cortex; III indicates that the nuclear opacity is aggravated, and meanwhile, the lens cortex is seen to be a bit and flaky opacity; IV indicates total opacity, complete opacity of the lens nucleus and cortex, and formation of mature cataract. The fractions are shown in Table 1 below.

TABLE 1 influence of lysine aescine on lenticular opacity grading in cataractous mice

Note: the data in the table are the 21 day scores.

The results show that on the 7 th day after injection administration, part of rat lens nuclei begin to have vacuole, water crack, irregular shape and unequal size, and then all the lens nuclei are cloudy and rapidly aggravate; the turbidity density increased at day 9, the area increased and spread to the cortex; swollen herringbone seams can be seen in the lens nucleus on day 11, and the cortex is somewhat flaky and turbid; the turbid area of the skin is gradually enlarged and the density is gradually increased on day 12; cataract formation was visible on day 14, indicating successful molding.

On day 21 after administration, the model group had significantly higher lens turbidity levels than the blank control group; compared with the model group, the positive control group and the lysine aescin high and medium dosage group have obviously lower lens opacity grade than the model group (P <0.01), and the lysine aescin low dosage group is lower than the model group (P <0.05), which indicates that the lysine aescin has the function of delaying the formation and development of rat cataract; compared with the positive control group, the lysine aescin high and medium dose group has no significant difference compared with the positive control group (P >0.05), while the lysine aescin low dose group has a lower lens opacity grade than the positive control group (P <0.05), and the medium dose is selected better from the clinical treatment perspective.

Example 2 Ocular irritation test of escin and its salt

Test drugs:

0.8% lysine aescin eye drops: dissolving lysine aescin 0.8g, sodium chloride 1g and borate 0.5g in water for injection to 100g, filtering, and sterilizing with flowing steam.

1.2% lysine aescin eye drops: dissolving 1.2g of lysine aescin, 1g of sodium chloride and 0.5g of borate in water for injection to 100g, filtering, and sterilizing with flowing steam.

0.8% sodium aescinate eye drops: dissolving sodium aescinate 0.8g, sodium chloride 1g and borate 0.5g in water for injection to 100g, filtering, and sterilizing with flowing steam.

1.2% sodium aescinate eye drops: dissolving sodium aescinate 1.2g, sodium chloride 1g and borate 0.5g in water for injection to 100g, filtering, and sterilizing with flowing steam.

The method comprises selecting 16 healthy rabbits, randomly dividing into 4 groups, including lysine aescin 0.8%, 1.2% and sodium aescin 0.8%, 1.2%, and 4 rabbits each. Before administration, the cornea, iris and conjunctiva of the eyes of the rabbits were examined, and no pathological changes or inflammations existed. Dripping sodium aescinate or lysine aescinate eye drops into conjunctival sac of left eye of each rabbit for 2 drops, passively closing for 10s, and administering physiological saline with the same amount to right eye 2 times daily for 7 days. Ocular changes were observed and recorded before and after the last dose each day. The degree of eye irritation of the tested drug is judged according to the eye irritation response scoring standard, the degree of eye irritation is 0-3.9 points without irritation, 4-8.9 points with mild irritation, 9-12.9 points with moderate irritation and 13-16 points with intensity irritation, and the scoring results are shown in Table 2.

TABLE 2 Effect of aescin and its salts on eye irritation in rabbits

The results show that the 0.8% lysine aescin group has no obvious irritation to the eyes of the rabbits; mild irritation occurred in two of the 1.2% lysine aescin groups; one of the 0.8% sodium aescinate groups showed mild irritation; in the 1.2% sodium aescinate group, mild irritation occurred in two cases and moderate irritation occurred in one case. In general, the irritation of the lysine aescin eye drops is obviously lower than that of the aescin sodium eye drops, which shows that the lysine aescin has better safety than the aescin sodium; meanwhile, the treatment by adopting 0.8 percent of aescine and salts thereof can not only ensure the curative effect, but also have better safety.

EXAMPLE 3 typical cases

Wang in a certain age, woman 73 years old, in 2015 in 11 months in first diagnosis. Chief complaints are blurred vision, photophobia and blurred vision. The examination shows that the eyes have 0.13 vision, conjunctiva is not hyperemic, the cornea is transparent, the pupil is of equal size, the light reflection is good, the iris and the ciliary body are not hyperemic, the crystalline lens is gray and is turbid, and the vitreous body is not turbid. The eye fundus peeping is not abnormal, which is diagnosed as the late mature period of senile cataract of both eyes, the lysine aescine eye drops are used for treating 21 days, the vision of both eyes is improved to 0.5, 30 days is a treatment course, and the vision of both eyes is improved to 0.7. After the pupil is dilated, the slit lamp examination shows that the lens opacity disappears, and the eyesight is stable after 6 months of follow-up visit.

Claims (1)

1. An application of eye drop containing lysine aescin 0.8% in preparing medicine for treating cataract is disclosed.