JP2015196673A - Asthenopia and/or dry eye prophylactic and/or therapeutic composition - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an asthenopia and/or dry eye prophylactic and/or therapeutic composition.SOLUTION: This invention provides a composition comprising hot water extract of blueberry leaves.

Description

  The present invention relates to a composition for preventing and / or treating eye strain and / or dry eye, and uses of the composition as a food and a medicine.

  Today, there are many scenes where the eyes are abused with things such as mobile devices, personal computers, televisions, videos, or video games, and many people complain of eyestrain and dry eyes. Drugs, health foods, sanitary products and the like effective for improving or preventing these symptoms are desired.

  By the way, about the leaf of blueberry, although the use of cancer cell growth suppression, hepatitis C virus production suppression, angiotensin converting enzyme inhibition, liver protection, or liver fat accumulation suppression has been reported (patent documents 1-5), It has not been known to be useful for treating or preventing eyestrain and dry eye.

JP 2007-22929 A JP 2007-119398 A JP 2007-217406 A JP 2008-174479 A JP 2008-189931 A

  The present invention has been obtained in the course of studying the effect of blueberry leaves on the human body, and an object thereof is to provide novel medicines and foods using blueberry leaves.

As a result of intensive studies, the present inventors have found that blueberry leaf-derived substances improve symptoms of eye strain and dry eye, and have completed the present invention.
That is, the present invention relates to a composition for preventing and / or treating eye strain and / or dry eye, comprising a product derived from blueberry leaves.

  The composition of the present invention has an effect of improving symptoms of eye strain and dry eye. In addition, the composition of the present invention is less likely to cause side effects even when taken for a long time, and has high safety.

The blueberry leaf-derived material used in the present invention is not particularly limited as long as it is obtained from the leaves of plants belonging to the genus Ericaceae (Vaccinium) (hereinafter also referred to as “blueberries”). , For example, the leaves themselves (raw leaves or leaves that have been treated such as drying); leaf strips, powders (eg, dried and powdered leaves), and suspensions thereof; Examples thereof include extracts such as squeezed juice, extract, concentrated extract, and extract powder; and purified products obtained by purifying the extract. A blueberry leaf extract, particularly a dry extract powder is preferred in that good eye strain or dry eye improvement effect can be obtained.
Moreover, in this invention, only 1 type may be used for said blueberry leaf origin, and 2 or more types may be used together.

  Examples of the blueberry include V. virgatum, V. shei, V. australe, V. corymbosum, V. myrtillus, or V. angustifolium, but in terms of obtaining a good eye strain or dry eye improvement effect, V. virgatum (rabbit eye blueberry) is preferred.

  The blueberry leaves used in the present invention are preferably leaves from the time of germination until before autumn leaves in that good eye strain or dry eye improvement effect can be obtained.

  The blueberry leaf strip used in the present invention may be obtained by cutting a raw leaf or a leaf that has been treated such as drying into thin pieces, and may further be subjected to a treatment such as drying. .

  The blueberry leaf powder used in the present invention may be obtained by pulverizing the blueberry leaf or strip, and the obtained powder may be subjected to a treatment such as drying.

The blueberry leaf extract used in the present invention may be obtained by squeezing or extracting the above-mentioned blueberry leaf, its strips, their powders, etc. according to a conventional method. Extraction with a solvent such as alcohol or a polar solvent is preferred from the viewpoint of obtaining an effect of improving fatigue or dry eye.
Ethanol can be used as the alcohol, and water or the like can be used as the polar solvent, and these solvents can be used alone or in admixture of two or more as required. In particular, water, particularly hot water is preferable from the viewpoint of obtaining excellent eye strain or dry eye improvement effect.
Further, the extraction operation may be performed a plurality of times with the same or different solvents, for example, using an extract obtained by further extracting an extract obtained from water or hot water from blueberry leaves with ethanol. Also good.

Extraction is carried out by adding a solvent to the leaves of blueberries, their fragments, or their powders and stirring as necessary, but the temperature, time, and solid-liquid ratio are not particularly limited.
When water is used as the extraction solvent, hot water is preferable, and examples thereof include 20 to 100 ° C., preferably 60 to 100 ° C., and more preferably 80 to 100 ° C. If necessary, the obtained extract may be used as an extract after removing solids by an operation such as filtration or centrifugation. Further, the extract may be purified by a conventional method to obtain a purified product.
These extracts or purified products may be freeze-dried or spray-dried, preferably spray-dried, or concentrated under reduced pressure, and then freeze-dried or spray-dried, preferably spray-dried. The obtained extract or purified product can be in various forms such as liquid, powder, concentrated solution, paste, and can be widely used as necessary, but is preferably powder.

Spray drying is a drying method in which an extract or the like is sprayed into hot air to obtain a dry powder, and is roughly divided into three types: a rotating disk, a pressure nozzle, and a two-fluid nozzle. There is no limitation, and any method may be used.
Spray drying may be performed by a known method. For example, a spray drying apparatus may be used, but it is preferable to use a rotating disk type spray drying apparatus. The temperature at the inlet of spray drying is, for example, 70 to 200 ° C., preferably around 130 ° C., and the temperature at the outlet is, for example, 70 to 100 ° C., preferably 75 to 85 ° C.

  The drying in the present invention is not particularly limited as long as the object of the present invention is not impaired, and includes, for example, vacuum freeze drying, hot air drying, far-infrared drying, vacuum drying, microwave vacuum drying, and superheated steam drying. Can be used. Preferably, it is vacuum freeze-drying with little component change. The vacuum freeze-drying conditions cannot be specified because they vary depending on the state of raw materials such as blueberry leaves. For example, when fresh leaves are dried as they are, the freezing temperature is -30 ° C to -20 ° C, the drying temperature is -30 ° C to 30 ° C, and the drying time Is preferably in the range of 15 to 24 hours.

  The composition of the present invention may be a product derived from a blueberry leaf, for example, a blueberry leaf, or an extract or purified product itself, but other substances having an effect of improving eye strain or dry eye, Oxidizing substances such as astaxanthin, lutein, crocetin, anthocyanins may be included.

  The composition of the present invention may be a product derived from a blueberry leaf, for example, a blueberry leaf, or an extract or purified product itself, but as long as the effects of the present invention are not impaired, an excipient, a sweetener, an acidity It may contain additives, materials generally used in medicines, foods, etc., as well as additives, thickeners, fragrances, pigments, emulsifiers.

  The composition of the present invention is useful for preventing and / or treating eye strain and / or dry eye. The composition of the present invention may cause eye strain or dry eye symptoms such as eye fatigue, dry eyes, heavy eyes, bright light, blurred eyes, blurred eyes, blurred vision, eye pain, It is useful for the prevention or treatment of eye discomfort, stiffness of the waist and shoulders.

  The composition according to the present invention can be used as a food or animal feed, for example, as a health food, functional food, health supplement, specific health food, beauty food, or nutritional supplement (supplement). These foods and animal feeds may be in the form of, for example, drinking water such as tea and juice; and ice cream, jelly, candy, chocolate, chewing gum and the like. Moreover, the form of a liquid agent, a powder agent, a granule, a capsule, or a tablet may be sufficient. Here, animals for animal feed include all animals that require prevention or treatment of eye strain and dry eye, including pet animals, livestock animals, and animals raised in zoos.

  The composition concerning this invention can be used as a pharmaceutical or a quasi-drug. These drugs or quasi drugs can be administered orally, for example, in the form of powders, tablets, coated tablets, dragees, hard or soft gelatin capsules, solutions, emulsions, or suspensions. Rectally in the form of an agent; eg, in the form of an injection or infusion; locally or transdermally, eg, in the form of an ointment, cream, gel, or solution; eg, in the form of eye drops and eyewash It can also be administered topically to the eye; parenterally. Oral administration is preferred.

  When the composition of the present invention is used in the form of tablets, granules, or capsules, tableting aids, granule processing aids, capsule processing aids and the like can be used.

  The tableting processing aid is not particularly limited as long as it does not impair the effects of the present invention, and any sugar granule, sucrose, powdered sugar, reduced maltose starch syrup, lactose, glucose, pullulan, erythritol, starch, dextrin Surfactant, powder such as sugar, crystalline cellulose, gum arabic, okara, etc., dietary fiber such as corn protein, calcium phosphate, food extract, food dry powder, natural fruit juice powder, sucrose fatty acid ester Fats and oils such as fats and oils, glycerin and fatty acid esters, or various sweeteners used in chewable tablets (eating tablets), various acidulants and various flavorings, shellac as a coating material, corn protein, yeast cell wall, starch , Reduced maltose starch syrup, sugarless sugar coating, maltitol, g Serine, sorbitol, HPMC, HPC and the like are exemplified.

  The granule processing aid is not particularly limited as long as the effects of the present invention are not impaired, and any sugar such as granulated sugar, super white sugar, powdered sugar, reduced maltose starch syrup, lactose, glucose, pullulan, erythritol, starch, dextrin, etc. Examples thereof include dietary fibers such as crystalline cellulose and gum arabic, food calcium such as corn protein and calcium phosphate, food extracts, food dry powders, and natural fruit juice powders.

  The capsule processing aid is not particularly limited as long as the effects of the present invention are not impaired. Granulated sugar, fine white sugar, powdered sugar, reduced maltose starch syrup powder, lactose, glucose for preparing hard capsule type capsules , Pullulan, erythritol, starch, dextrin and other sugars, crystalline cellulose, dietary fiber such as gum arabic, food calcium such as corn protein and calcium phosphate, food extracts, food dried powders, natural fruit juice powder, etc., soft capsule type For example, content viscosity modifiers such as food fats and oils, beeswax, glycerin fatty acid esters, and the like for preparing capsules are exemplified.

  Tablets can usually be prepared using a tableting machine, but the tablets are blended with seasoning ingredients to make a chewable tablet, or the tablet surface is coated using an automatic coating machine, spray granulator or hand pan. Or you may. Various types of granulators such as a spray granulator type, a kneading (extruding) type, or a high-speed agitation granulator type can be used for forming the granules. For preparation of capsules, capsule filling machines (hard type and soft type) can be used by mixing capsule aids.

The amount of intake of the composition according to the present invention is not particularly limited, but can be appropriately selected according to the dosage form and the age, weight and symptoms of the intake person or intake animal such as the user or patient. For example, the amount of the active ingredient is about 0.1 g to about 50 g, preferably about 0.2 g to about 10 g, more preferably about 0, in terms of the dry weight of blueberry leaves per 60 kg of the body weight of the ingestor or ingestion animal per day. It is desirable to take 3 g to about 6 g orally in that good eye strain or a dry eye improvement effect can be obtained.
The intake period can be arbitrarily determined according to the age and symptoms of the intake person or animal.

  Hereinafter, the present invention will be described in more detail with reference to examples, but the present invention is not limited thereto.

1. Manufacture of blueberry leaf dry extract powder
The leaves of V. virgatum (rabbit eye blueberry) are frozen at -30 ° C, and then the maximum shelf temperature is 65 ° C, the final product temperature is 40 ° C, and the drying time is 25 hours, using a vacuum freeze dryer (Nihon Drives Co., Ltd.) It was lyophilized under vacuum conditions. The obtained freeze-dried leaves were pulverized by a pulverizer and passed through a 1.0 mm screen to obtain a lyophilized powder.
Next, 16 liters of distilled water at 90 to 100 ° C. was added to 1 kg of the obtained lyophilized powder, stirred for 1 hour while keeping the temperature, and then filtered under pressure (pressure 0.01 Mpa, pore size 293 mm) to obtain a filtrate. It was. The filtrate was concentrated with a vacuum concentrator, sterilized with a helicoid instantaneous heat sterilizer, and then spray-dried with a spray dryer to obtain a dry powder. This dry powder was mixed with a Boule container mixer to obtain 0.4 kg of blueberry leaf dry extract powder.

2. Production of Food Containing Blueberry Leaf Dry Extract Powder According to a conventional method, tablets of food containing blueberry leaf dry extract powder were produced. In addition, maltitol is usually blended for tablet binding purposes, seaweed powder for tablet weight stabilization purposes at the time of tablet molding, crystalline cellulose for tablet binding purposes, and powdered oils and fats for blending prevention purposes at the time of tablet molding. It is an additive.

3. Eye Function Effect Test The effect of the blueberry leaf dry extract powder-containing food produced above (hereinafter also referred to as “test food”) on eyestrain and dry eye was examined.
3.1. Subjects First, subjects who selected all of the following selection criteria and did not violate the exclusion criteria were selected as candidate subjects.
[Selection criteria]
(1) Men and women between the ages of 20 and 65 (2) Those who are aware of eye strain (3) Those who fall under two or more of the following dry eye diagnostic criteria A to C A: Awareness of dry eyes Symptoms B: Abnormal tears [5 mm or less by the Schirmer test I method or tear film destruction time (BUT) 5 seconds or less]
C: Keratoconjunctival epithelial disorder (fluorescein staining) score of 3 points or more (9 points maximum)
* Selected in descending order of the ability to adjust near points at the time of preliminary inspection.
[Exclusion criteria]
(1) Person with severe refractive error (2) Person who has regularly used health foods, quasi-drugs, and general medicines that are strengthened from blueberry leaves within one month before obtaining consent to participate in this study (3) Persons who have developed serious ophthalmic diseases or have a history (4) Persons with amblyopia and strabismus (5) Persons who may develop hay fever in the period from July to December ( 6) Those who are undergoing treatment that affects the results of the study or who are using pharmaceuticals (7) Those who have a serious illness and those with a history of it (8) May cause allergies due to the test food A person (9) A person who participated in another clinical study within one month before obtaining consent to participate in this study, or a person who plans to participate in another clinical study after obtaining consent for participation in this study (10) Those who plan to become pregnant or breastfeed during the test period (11) Practices from the answer to the questionnaire, a person who has been determined to be inappropriate as a subject (12) Other, who investigators has determined to be inappropriate as a subject

3.2. Exam Schedule 16 candidates suitable for the purpose of the test are tested for the above subjects as a pre-examination: lifestyle questionnaire, physical condition confirmation, physical measurement, physical examination, ophthalmic examination, general clinical examination, questionnaire survey. (9 men and 7 women) were selected as subjects.
This test subject was ingested with the test food produced as described above twice a day, twice a day, after breakfast and after dinner. The intake period was 8 weeks (56 days). In addition, the subjects had a diary recorded, and they visited the 4th and 8th weeks after the start of ingestion and were examined for efficacy evaluation items and safety evaluation items.
The efficacy endpoints are as follows: Peripheral control ability, tear secretion (Schirmer test I method), tear film destruction time (TBUT), keratoconjunctival epithelial disorder score, questionnaire, and secondary endpoints Completely corrected visual acuity and refractive power. The safety evaluation items were general clinical examination and physical examination.
Table 2 shows the contents of the above examination, questionnaire, and diary.

3.3. Test results All 16 subjects who started taking test foods completed the prescribed test schedule. However, out of 16 men, one man was found to have epidemic keratoconjunctivitis at the time of the 8th week examination, and another man was consistent with the number of test food intakes and diary entries. 14 were included in the effectiveness analysis exclusion criteria for ophthalmic examinations and questionnaires. There were no subjects whose test food intake rate was below 80%.
[Exclusion criteria for analysis]
(1) Persons whose intake rate of test food is less than 80% (2) Persons whose actions such as lack of diary records are seriously impaired in the reliability of test results (3) Exclusion criteria Those who became clear after enrolling in the study, those who were found to be unable to comply with the restrictions during the study period (4), and others who had an obvious reason to be excluded

  Table 3 below shows the background factors of the 14 effective analysis subjects.

About the ophthalmic examination which concerns on an efficacy evaluation item, since the test subject selection was performed based on the test value of the right eye at the time of a prior examination, the right eye was made into the evaluation object.
Tables 4 to 6 show changes in test values of the efficacy evaluation items. Each test value was expressed as an average value ± standard deviation. Moreover, the test value at each time point after ingestion was compared with the test value before ingestion using a one-sample t-test. However, for keratoconjunctival epithelial disorder score and Questionnaire 5 to Questionnaire 20, the survey results at each time point after ingestion were compared with the survey results before ingestion using Wilcoxon signed rank sum test. The significance level of the test was 5% on both sides.

From Table 4, TBUT, which is the main endpoint, was significantly increased and improved in the fourth week compared to before intake. In addition, the keratoconjunctival epithelial disorder score was significantly reduced at 4 weeks compared with before ingestion, indicating an improvement.
As for the questionnaire, from Table 5, questions 1 (the eyes are tired) at the 4th and 8th weeks, Q4 (the eyes feel dry), the 4th and 8th weeks, and the question 8 (shoulder, waist) 4th and 8th week of Gagaru, 8th week of Q14 (feels heavy), 4th week of Q15 (easy to feel dazzling), and 16 of Q16 (eyes gurgling) 4th and 8th week, Q18 (somehow discomforting to the eyes), 4th and 8th week surveys showed a significant decrease compared to before intake, showing improvement It was done.
Regarding safety evaluation items, there were no particularly problematic findings, and the safety of the test food could be confirmed.
From the above results, it was shown that ingestion of blueberry leaf dry extract powder improves tear fluid stability, improves the ocular surface environment, and further improves the symptoms of eye strain and dry eye. Also, there was no problem with the safety of the dried blueberry leaf extract powder.

  The composition of the present invention can be used to improve eye strain and / or dry eye. This composition can be used as a pharmaceutical or a food such as a health food, a health supplement, a food for specified health use, or a nutritional supplement for the above-mentioned purposes.

Claims (5)

  A composition for preventing and / or treating eye strain and / or dry eye, comprising a product derived from blueberry leaves.   The composition according to claim 1, wherein the blueberry leaf-derived material is an extract of blueberry leaves.   The composition according to claim 1 or 2, wherein the blueberry leaf-derived material is a hot water extract of blueberry leaves.   The composition according to any one of claims 1 to 3, which is a food.   The composition according to any one of claims 1 to 3, which is a pharmaceutical product.