Method for ameliorating dry eye syndrome using ethanol-distilled product of soybean seeds

Abstract

The present invention discloses that an ethanol-distilled product of soybean seeds can be used to ameliorate dry eye syndrome.

Description

Method for improving dry eye using ethanol distillation product of soybean seeds Technical Field

[0001] The present invention relates to a method for improving dry eye syndrome using an ethanol-distilled product of Glycine max seeds. Background Art

[0002] Dry eye syndrome (DES) is primarily caused by insufficient tear secretion and excessive tear evaporation. Symptoms include dryness, redness, itching, photophobia, and pain. Severe symptoms may even lead to visual disturbances and ocular surface damage.

[0003] Clinically, dry eye syndrome is primarily treated with artificial tears for mild cases, while severe cases require anti-inflammatory drugs (SAIDs). However, both artificial tears and SAIDs can only temporarily alleviate eye discomfort and do not increase tear production.

[0004] Soybean (Glycine max) is a plant of the genus Glycine in the family Fabaceae. Its seeds are primarily used and are considered a good source of protein. In TW I640318 B (corresponding to US 10543243 B2), the applicant disclosed an extract composition comprising an extract obtained by extracting soybean seeds using water or 90% or less ethanol by weight, and a distillation product obtained by distilling the soybean seeds using water or 15% or less ethanol by weight. This extract composition has been shown to promote skin wound healing and nerve cell proliferation, as well as treat dementia and breast cancer. In TW I724417 B (corresponding to US 11083766 B2), the applicant disclosed the use of this extract composition to alleviate pain and skin inflammation caused by cancer radiation therapy.

[0005] As far as the applicant is aware, there has been no literature or prior patent application that has ever disclosed that soybean seed distillate can be used to improve dry eye syndrome. Summary of the Invention

[0006] In the present invention, the applicants have experimentally discovered that an ethanol-distilled product of Glycine max seeds can effectively increase tear secretion in mice with scopolamine-induced dry eye syndrome, and is therefore believed to have the effect of improving dry eye syndrome.

[0007] Therefore, in a first aspect, the present invention provides a method for improving dry eye, comprising administering a medicament comprising the soybean seed ethanol distillation product described above to a subject in need thereof.

[0008] In a second aspect, the present invention provides a use of the ethanol distillation product of soybean seeds as described above for preparing a medicine for improving dry eye.

[0009] In a third aspect, the present invention provides a medicine for improving dry eye, comprising the ethanol distillation product of soybean seeds as described above.

[0010] Preferably, the ethanol distillation product is obtained by distilling soybean seeds using 0.01 wt% to 15 wt% of ethanol.

[0011] Preferably, the ethanol distillation product is obtained by distilling soybean seeds using 0.13 wt % to 15 wt % of ethanol.

[0012] Preferably, the medicine further comprises a pharmaceutically acceptable carrier.

[0013] Preferably, the pharmaceutical product is in a dosage form for oral administration, topical administration or parenteral administration. BRIEF DESCRIPTION OF THE DRAWINGS

[0014] The above and other objects, features and advantages of the present invention will become apparent after referring to the following detailed description and preferred embodiments and the accompanying drawings, in which:

[0015] FIG1 shows the wet lengths measured for the mice in each group in Example 1 below, wherein “*” and “**” indicate p < 0.05 and p < 0.01, respectively, when compared with the pathological control group; and “#” and “##” indicate p < 0.05 and p < 0.01, respectively, when compared with the comparison group. DETAILED DESCRIPTION

[0016] For the purposes of this specification, it will be expressly understood that the word "comprising" means "including, but not limited to," and that the word "comprises" has a corresponding meaning.

[0017] Unless otherwise defined, all technical and scientific terms used herein have the same meanings as those commonly understood by those skilled in the art. Those skilled in the art will recognize many methods and materials similar or equivalent to those described herein that can be used to practice the present invention. Of course, the present invention is in no way limited to the methods and materials described.

[0018] The present invention provides an ethanol-distilled product of soybean seeds (Glycine max seed) for use in preparing a medicine for improving dry eye syndrome.

[0019] In addition, the present invention also provides a medicine for improving dry eye, which comprises the soybean seed ethanol distillation product described above.

[0020] As used herein, the terms "dry eye syndrome," "xerophthalmia," "sclerophthalmia," "keratoconjunctivitis sicca," and "dysfunctional tear syndrome" are used interchangeably and are intended to encompass at least one of the following forms: aqueous tear-deficient dry eye, mucin-deficient dry eye, lipid-deficient dry eye, and evaporative dry eye.

[0021] Dry eye, to which the present invention is applicable, can be caused by a variety of factors, including, but not limited to: a deficiency in the tear-flow system; sleep disorders, such as insomnia and sleep apnea syndrome; the natural aging process, particularly menopause; side effects of medications (e.g., antidepressants, blood pressure medications, Parkinson's medications, antihistamines, and birth control pills); diseases that affect tear production, such as Sjogren's syndrome, rheumatoid arthritis, and collagen vascular disease; contact lens wear; smoking; and particulate matter (PM), such as PM. 2.5; dry climate; insufficient blinking; and structural problems that prevent the eyelid from closing properly.

[0022] As used herein, the terms "soybean (Glycine max)", "edamame (Glycine max)", "soybean (Glycine max)", and "soybean" are used interchangeably and are intended to encompass soybeans that are readily available to those skilled in the art or that are collected from natural sources.

[0023] According to the present invention, the method for ethanol distillation from soybean seeds can be performed using techniques well known and commonly used by those skilled in the art. In this regard, reference can be made, for example, to TW 1724417 B (corresponding to US 11083766 B2) and TW 1640318 B (corresponding to US 11452753 B2, US 11400128 B2, and US 10543243 B2).

[0024] It is understood that the operating conditions for the soybean seed ethanol distillation method may be further varied depending on factors such as the soybean seed processing method and the ratio of soybean seed to ethanol to achieve optimal extraction results. The selection of these operating conditions is a matter of routine discretion for those skilled in the art.

[0025] According to the present invention, ethanol distillation of soybean seeds can be performed using fresh soybean seeds, or can be performed using soybean seeds that have previously undergone a processing selected from the group consisting of: drying, grinding, chopping, pulverizing, and combinations thereof.

[0026] According to the present invention, the ethanol distillation can be performed using soybean seeds and ethanol solution in a weight ratio of 1:1 to 1:100. In a preferred embodiment of the present invention, the weight ratio is 1:10.

[0027] According to the present invention, the ethanol distillation can be performed by using 0.01 wt % to 15 wt % ethanol. Preferably, the ethanol distillation can be performed by using 0.13 wt % to 15 wt % ethanol. In a preferred embodiment of the present invention, the ethanol distillation is performed by using 0.13 wt % ethanol.

[0028] According to the present invention, the ethanol distillation can be carried out at a temperature of 55° C. to 98° C. In a preferred embodiment of the present invention, the temperature is 90° C.

[0029] According to the present invention, the pharmaceutical product may be in a dosage form suitable for parenteral administration, oral administration, or topical administration.

[0030] According to the present invention, the pharmaceutical product may further comprise a pharmaceutically acceptable carrier widely used in pharmaceutical manufacturing technology. For example, the pharmaceutically acceptable carrier may comprise one or more agents selected from the following: solvent, buffer, emulsifier, suspending agent, decomposer, disintegrating agent, dispersing agent, binding agent, excipient, stabilizer, chelating agent, diluent, gelling agent, preservative, wetting agent, lubricant, absorption delaying agent, liposome, thickener, and the like. The selection and amount of these agents are within the professional knowledge and routine skills of those skilled in the art.

[0031] According to the present invention, the pharmaceutical product can be manufactured into a dosage form suitable for parenteral administration (including injection, for example, a sterile aqueous solution or dispersion) using techniques well known to those skilled in the art, and administered by a route selected from the group consisting of intraperitoneal injection, intrapleural injection, intramuscular injection, intravenous injection, intraarterial injection, intraarticular injection, intrasynovial injection, intrathecal injection, intracranial injection, intraepidermal injection, subcutaneous injection, intradermal injection, intralesional injection, and sublingual administration.

[0032] According to the present invention, the pharmaceutical product can be manufactured into a dosage form suitable for oral administration using techniques well known to those skilled in the art, including, but not limited to, sterile powders, tablets, troches, lozenges, pellets, capsules, dispersible powders or granules, solutions, suspensions, emulsions, syrups, elixirs, slurries, and the like.

[0033] According to the present invention, the pharmaceutical product can be manufactured into an external preparation suitable for topical application to the skin using techniques well known to those skilled in the art, including, but not limited to, emulsions, gels, ointments, creams, patches, liniments, powders, aerosols, sprays, lotions, serums, pastes, foams, drops, suspensions, salve and bandages.

[0034] According to the present invention, the external preparation is prepared by mixing the pharmaceutical of the present invention with a base well known to those skilled in the art.

[0035] According to the present invention, the base may contain one or more additives selected from the group consisting of water, alcohols, glycols, hydrocarbons (such as petroleum jelly and white petrolatum), waxes (such as paraffin and yellow wax), preservatives, antioxidants, surfactants, absorption enhancers, stabilizers, gelling agents, 941( 941), microcrystalline cellulose, and carboxymethylcellulose] active agents, humectants, odor absorbers, fragrances, pH adjusting agents, chelating agents, emulsifiers, occlusive agents, emollients, solubilizing agents, penetration enhancers, thickeners, anti-irritants, preservatives, colorants, and propellants. The selection and amount of these additives are within the professional knowledge and routine skills of those skilled in the art.

[0036] Preferably, the pharmaceutical product is an external preparation comprising 1 wt% to 20 wt% of a thickener and 1 wt% to 10 wt% of a preservative. In a preferred embodiment of the present invention, the pharmaceutical product is an ointment comprising 9.65 wt% of a thickener and 0.35 wt% of a preservative.

[0037] In a preferred embodiment of the present invention, the thickener is polyacrylic acid (carbomer), glyceryl polyacrylate, and hyaluronic acid.

[0038] In a preferred embodiment of the present invention, the preservatives are benzyl alcohol and chloroxylenol.

[0039] The present invention also provides a method for improving dry eye, comprising administering the above-mentioned pharmaceutical to a subject in need thereof.

[0040] As used herein, the terms "administration" and "administration" are used interchangeably and mean introducing, providing or delivering a predetermined active ingredient to a subject by any appropriate route to perform its intended effect.

[0041] As used herein, the term "subject" means any mammal of interest, such as humans, monkeys, cows, sheep, horses, pigs, goats, dogs, cats, mice, and rats.

[0042] According to the present invention, the dosage and frequency of administration of the soybean seed ethanol distillate product will vary depending on the severity of the condition being treated, the route of administration, and the age, physical condition, and response of the individual being treated. Generally, the soybean seed ethanol distillate product can be administered as a single dose or divided into several doses. For example, the soybean seed ethanol distillate product can be administered twice daily.

[0043] The present invention will be further described with reference to the following examples. However, it should be understood that these examples are for illustration only and should not be construed as limitations on the implementation of the present invention.

[0044] <Example>

[0045] Example 1. Evaluation of the efficacy of ethanol-distilled product from soybean seeds (Glycine max seed) in improving dry eye syndrome

[0046] Experimental Materials:

[0047] 1. Preparation of ethanol distillation product from soybean seeds:

[0048] The soybean seed ethanol distillate used in this example was prepared by referring to the method described in the examples of TW I640318 B (corresponding to US 10543243 B2).

[0049] Briefly, soybean seed powder collected from Tainan City was mixed with 0.13 wt % ethanol at a weight ratio of 1:10, and then distilled at 90° C. and the condensate was collected to obtain an ethanol distillation product of soybean seeds.

[0050] 2. Preparation of an ointment containing an ethanol distillation product of soybean seeds:

[0051] Ointments 1 to 3 used in this example had the formulations shown in Table 1 below. Ointment 2 was prepared according to the following steps: soybean seed ethanol distillate was dissolved in water and heated to a temperature between 95°C and 100°C. Polyacrylic acid (carbomer), glyceryl polyacrylate, and hyaluronic acid were then added and stirred. After the resulting mixture cooled, benzyl alcohol and chloroxylenol were added. The preparation steps for Ointments 1 and 3 were identical to those for Ointment 2, except that ointment 1 did not contain soybean seed ethanol distillate, and ointment 3 did not contain soybean seed ethanol distillate dissolved in water before heating.

[0052] Table 1. Formulas of various ointments

[0053] 3. Experimental Animals

[0054] Male C57BL / 6 mice (8 weeks old, weighing approximately 24 g) used in this example were purchased from BioLasco Taiwan Co., Ltd. All experimental animals were housed in an animal room with a 12-hour light and dark cycle, maintained at 24-26°C and a relative humidity of 55%-65%, and provided with ample water and feed. Animal handling and experimental procedures complied with the standards of the Association for Assessment and Accreditation of Laboratory Animal Care (AALAC) International.

[0055] Experimental methods:

[0056] A. Causes of dry eye:

[0057] First, mice were randomly divided into five groups: a normal control group (n=4), a pathological control group (n=5), a comparative group (n=4), experimental group 1 (n=5), and experimental group 2 (n=4). Mice in the pathological control group, the comparative group, and experimental groups 1 and 2 were then given subcutaneous injections of scopolamine (Sigma, Catalog No. S0929) (0.5 mg / mouse, dissolved in 0.2 mL of saline) twice daily to induce dry eye. Mice in the normal control group received no treatment.

[0058] B. Dosage for dry eye:

[0059] On the first day after the initial scopolamine injection, ointments 1 to 3 (50 mg per 1 square centimeter) were applied to the skin around the eyes of mice in the control group and experimental groups 1 and 2, respectively, twice daily for a total of 21 days. Mice in the normal control and pathological control groups received no treatment.

[0060] C. Schirmer tear test

[0061] On the 21st day after the start of scopolamine injection, 1×40mm 2 A Schirmer tear test strip (purchased from OPTITECH) was placed on the right lower eyelid of each group of mice for 30 seconds, and then the wetted length was measured and recorded.

[0062] The experimental data were expressed as mean ± standard error of the mean (SEM) and analyzed using Student's t-test to assess differences between groups. Statistical significance was indicated if p < 0.05.

[0063] result:

[0064] Figure 1 shows the measured wet lengths for each group of mice. As shown in Figure 1, the wet lengths of the pathological control group were significantly lower than those of the normal control group, indicating that scopolamine successfully induced dry eye and tear deficiency in the mice. Compared to the pathological control group and the control group, the wet lengths of experimental groups 1 and 2 were significantly increased, and this increase became more pronounced with increasing levels of soybean seed ethanol distillate. These results demonstrate that soybean seed ethanol distillate can increase tear secretion in a dose-related manner. Therefore, soybean seed ethanol distillate is considered to have high potential for the development of pharmaceuticals to improve dry eye.

[0065] All patents and publications cited in this specification are hereby incorporated by reference in their entirety. In the event of any conflict, the detailed description of this specification (including definitions) will prevail.

[0066] Although the present invention has been described with reference to the specific embodiments above, it is apparent that many modifications and variations can be made without departing from the scope and spirit of the invention. It is therefore intended that the present invention be limited only as indicated by the appended claims.

Claims

1. A soybean seed ethanol distillation product for use in preparing a pharmaceutical product for improving dry eye syndrome.

2. The method according to claim 1, characterized in that The ethanol distillation product is prepared by distilling soybean seeds using 0.01 wt % to 15 wt % of ethanol.

3. The method according to claim 1, characterized in that The ethanol distillation product is prepared by distilling soybean seeds using 0.13 wt % to 15 wt % of ethanol.

4. The method according to claim 1, characterized in that The pharmaceutical product further comprises a pharmaceutically acceptable carrier.

5. The method according to claim 1, characterized in that The pharmaceutical product is in a dosage form for oral administration, topical administration or parenteral administration.

6. A method for improving dry eye, characterized in that: The method includes administering to a subject in need thereof a medicament comprising an ethanol distillation product of soybean seeds.

7. The method according to claim 6, characterized in that The ethanol distillation product is prepared by distilling soybean seeds using 0.01 wt % to 15 wt % of ethanol.

8. The method according to claim 6, characterized in that The ethanol distillation product is prepared by distilling soybean seeds using 0.13 wt % to 15 wt % of ethanol.

9. The method according to claim 6, characterized in that The pharmaceutical product further comprises a pharmaceutically acceptable carrier.

10. The method according to claim 6, characterized in that The pharmaceutical product is in a dosage form for oral administration, topical administration or parenteral administration.

11. A pharmaceutical product for improving dry eye syndrome, characterized in that: The medicament comprises an ethanol distillation product of soybean seeds.

12. The pharmaceutical product according to claim 11, characterized in that The ethanol distillation product is prepared by distilling soybean seeds using 0.01 wt % to 15 wt % of ethanol.

13. The pharmaceutical product according to claim 11, characterized in that The ethanol distillation product is prepared by distilling soybean seeds using 0.13 wt % to 15 wt % of ethanol.

14. The pharmaceutical product according to claim 11, characterized in that The pharmaceutical product further comprises a pharmaceutically acceptable carrier.

15. The pharmaceutical product according to claim 11, characterized in that The pharmaceutical product is in a dosage form for oral administration, topical administration or parenteral administration.

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