COMPOSITION OF A DIETARY SUPPLEMENT AND/OR A NUTRITIONAL ADDITIVE FOR FOOD, A UNITARY DOSAGE FORM OF SAID COMPOSITION, AND THEIR USE FOR IMPROVEMENT OF THE QUALITY OF VISUAL PERFORMANCE INCLUDING CONTRAST SENSITIVITY IN PERSONS IN NEED OF SUCH AN IMPROVEMENT, INCLUDING PERSONS SUFFERING FROM AT LEAST ONE EYE DISEASE, PARTICULARLY VITREOUS FLOATERS

Abstract

Provided are a composition of a dietary supplement and a nutritional additive for food, a unitary dosage form of said composition, and their use for the improvement of the quality of visual performance including contrast sensitivity. An illustrative composition of the present disclosure includes as active substances L-lysine, vitamin C, zinc, grape extract and bitter orange extract in therapeutically effective quantities, and optionally at least one excipient. In some embodiments, the percentages of the individual active substances relative to the sum of the percentages of all active substances are about 50% by weight of L-lysine, about 15% by weight of vitamin C, about 2% by weight of zinc, about 10% by weight of the grape extract and about 23% by weight of the bitter orange extract, with all percentages of the individual active substances adding up to 100% by weight of all active substances.

Claims

1. A composition of a dietary supplement and/or nutritional additive for food comprising L-lysine, vitamin C, zinc, grape extract and bitter orange extract in therapeutically effective quantities as active substances, and potentially at least one excipient, wherein percentages of the individual active substances relative to a sum of percentages of all active substances are: a) about 50% by weight of L-lysine, b) about 15% by weight of vitamin C, c) about 2% by weight of zinc, d) about 10% by weight of the grape extract, e) about 23% by weight of the bitter orange extract, with all percentages of the individual active substances adding up to 100% by weight of all active substances.

2. The composition according to claim 1 comprising: a) from about 125 mg to about 250 mg of L-lysine, b) from about 40 mg to about 80 mg of vitamin C, c) from about 5 mg to about 10 mg of zinc, d) from about 25 mg to about 50 mg of the grape extract, e) from about 60 mg to about 120 mg of the bitter orange extract.

3. The composition according to claim 1, wherein the ingredients constitute a mixture.

4. The composition according to claim 1, wherein the grape extract and/or the bitter orange extract are selected from the group comprising the extract of fruit seeds, the extract of fruit pulp, the extract of fruit skin, the extract of blossoms of these plants, or their combinations.

5. The composition according to claim 1, wherein the grape extract is a grape extract of the Vitis vinifera species and/or the bitter orange extract is a bitter orange extract of Citrus aurantium species, preferably, both extracts DER 100:1 (“DER” means drug extract ratio, which is a ratio of the quantity of the plant raw material used for producing the plant extract to the quantity of the obtained plant extract).

6. The composition according to claim 1, wherein the excipient is a substance nutritionally permitted and is selected from the group comprising at least a vehicle agent, a bulking agent, a binding agent, a disintegrant, a surfactant, a lubricant, an anti-caking agent, an acidity regulator, an antioxidant, a synthetic and/or natural colourant, a colour retaining substance, an emulsifier, a sweetener, an aromatizing agent, a flavouring agent, a flavour enhancer, a preservative, a stabilizing agent, a solvent and a diluent, or their mixtures.

7. The composition according to claim 1, wherein the composition is formed as a powder, a granulate, a liquid, or a gel of any formulation adequate for oral application.

8. The composition according to claim 1 applied in a preferred dose, frequency and a form for a period of at least 2 months.

9. The composition according to claim 1 a unitary dosage form.

10. The composition according to claim 9, wherein the unitary dosage form contains a daily dose of active substances of the present composition.

11. The composition according to claim 9, wherein the unitary dosage form is further prepared in a form selected from the group comprising at least a capsule, a tablet, a sachet, a “stick-type” sachet and an ampoule, including any of the forms ensuring a prolonged release of the active substances of the composition in time of at least 3 hours after consumption.

12. A composition of a dietary supplement and/or nutritional additive for food according to claim 1 for use to improve quality of visual performance including contrast sensitivity in persons in need of such an improvement and with the objective to improve quality of life of the persons.

13. A composition of a dietary supplement and/or a nutritional additive for food according to claim 1 for use in treating eye diseases and/or slowing down development of eye diseases and/or inhibiting development of eye diseases and/or preventing the eye diseases.

14. The composition according to claim 12 for use in persons suffering from vitreous floaters.

15. A use of a composition of a dietary supplement and/or nutritional additive for food according to claim 1 for improving quality of visual performance including contrast sensitivity in persons in need of such an improvement and for improving quality of life of the persons.

16. A use of a composition of a dietary supplement and/or nutritional additive for food according to claim 1 for treating eye diseases and/or slowing down development of eye diseases and/or inhibiting development of eye diseases and/or for prevention of the eye diseases.

17. The use of the composition according to claim 15 in persons suffering from vitreous floaters.

18. The composition according to claim 13 for use in persons suffering from vitreous floaters.

Description

PREFERRED EMBODIMENT OF THE PRESENT INVENTION

[0100] 61 patients suffering from vitreous floaters were randomized in a 50:50 fashion into the active group (n=31) or the control group (n=30). The active group received the composition according to the present invention formulated as the mixture from the powdered active substances in respective percentages by weight and closed in the unitary dosage form in the form of the capsule. One capsule contained 125 mg of L-lysine, 40 mg of vitamin C, 5 mg of zinc, 25 mg of the Vitis vinifera grape extract DER 100:1 and 60 mg of the Citrus aurantium bitter orange extract DER 100:1. The patients from the active group consumed the composition according to the present invention in the amount of one capsule a day for 6 months. The control group received a placebo capsule containing microcrystalline cellulose which had similar shape and colour to the capsule containing the tested composition according to the present invention.

[0101] For the subjective assessment of the impact of vitreous floaters on quality of life at the baseline and at the end of the study, a customized, non-standardized questionnaire on visual disturbances caused by vitreous floaters was employed, as presented below towards the end of the present description.

[0102] The contrast sensitivity parameter (Multiquity LogCS Score), which is an objective assessment parameter of the quality of visual performance, was measured for each patient before and after supplementation, using the MiQ Contrast 256 test, Smolarek-Kasprzak, P., et al., “Measuring visual function using the MultiQuity system: Comparison with an established device”, Journal of ophthalmology, 2014. Binocular contrast thresholds (%) in photopic and mesopic conditions were measured with the Acuity-plus test from the Advanced Vision and Optometric Test (AVOT). Retinal function (rods and cones) was assessed with the Flicker-plus test from the AVOT suite, which employs a 15Hz flicker stimulus. Macular Pigment (MP) was measured with the use of the multi-colour Heidelberg Spectralis HRA+OCT test from Heidelberg Engineering GmbH, Heidelberg, Germany.

[0103] For the assessment of the safety of the composition according to the present invention on the organisms of the patients, apart from the clinical studies, also biochemical blood tests were performed, that is a complete blood morphology and biochemistry of the blood serum.

Alterations in the Increase of Vitreous Floaters Disturbances in the Course of 6 Months of Supplementation

[0104] To assess the degree of the increase in changes connected with vitreous floaters in the subjective perception of the patients, they were asked about visual disturbances caused by floaters in the course of past 6 months prior to enrolment into the study (baseline visit) and following six months of supplementation (final study visit). The question offered a 3-response choice, which was scored as follows: My condition has been stable and I have not been bothered by my floaters—0, My floaters have been observed intermittently/were moderately bothersome—3, My floaters have been consistently bothersome—6. A score of 3 signified a moderate increase in the symptoms, with increasing severity denoted by a progress towards a score of 6.

[0105] At baseline, the median score (IQR, Interquartile Range) for both the control as well as active groups was 3.00 (3.00-6.00) and did not differ significantly (p=0.689; Mean±SD score of 3.69±1.54 and 3.90±1.40 for the control and active groups, respectively). Following supplementation, the median score (IQR) recorded was 3.00 (3.00-6.00) and 3.00 (0.00-3.00) for the control and active groups, respectively, the difference between them being statistically significant (p=0.018; Mean±SD score of 3.35±1.96 and 2.10±1.79 for the control and active groups, respectively).

[0106] At baseline, in the control group 1 subject (3.85%) reported being stable and not feeling the presence of floaters, 20 subjects (73.07%) reported occasional disturbances caused by their floaters, and 9 subjects (23.08%) reported being constantly bothered by their floaters. Following supplementation, 4 subjects (15.38%) reported that they have not paid attention to their vitreous floaters after the follow-up visit (p=0.564) whereas 7 subjects (26.92%) reported being constantly bothered by their floaters. The 11.53% increase was thus noted in the category “no bother from floaters”, and the 3.84% increase in the category “persistent disturbances from floaters”, for the control group after supplementing for 6 months.

[0107] In summary, for the control group the self-reported results of the subjects proved that the state of 14 subjects (53.85%) remained without changes, the state of 7 subjects (26.92%) improved, and the state of 5 subjects (19.23%) deteriorated, in the supplementation time from the baseline until the final visit.

[0108] In the active group, which was supplemented with the composition according to the present invention, at baseline 1 subject (3.33%) reported being stable and not feeling the presence of floaters, 20 subjects (66.67%) reported moderate disturbances from their floaters, and 9 subjects (30%) reported that the floaters were constantly bothersome prior to enrolment into the study. After supplementation for 6 months, 11 subjects (36.67%) reported that they do not feel the presence of floaters (p=0.001). Also, 2 subjects (6.67%) reported being constantly bothered by their floaters following supplementation. As a result, there was the increase of 33.34% in the number of the patients reporting the lack of floaters, and the decrease of 23.33% in the number of the patients reporting constant disturbances from floaters after the 6-month supplementation period. In summary, for the active group, the results reported by the patients proved that the state of 12 subjects (40%) remained without changes, the state of 16 subjects (53.33%) improved, and the state of 2 subjects (6.67%) deteriorated, in the time between the baseline visit and the visit after 6 months of supplementation. See Table 1 below.

TABLE-US-00001 TABLE 1 Changes in the frequency of reported disturbances from vitreous floaters in the control and active groups after 6 months of supplementation Active Group (supplemented with the Control Group composition according (placebo) to the present invention) number of tested patients number of tested patients Without 14 12 changes Improvement 7 16 Deterioration 5 2

Change in the Assessment of the Impact of Vitreous Floaters on Daily Life in the Control and Active Groups after 6 months of Supplementation

[0109] The study assessed the impact of vitreous floaters on the daily life of the patients before and after the 6-month supplementation on a 5-point scale: no impact, a small impact, a moderate impact, a great impact and a very significant impact, and this impact was assessed on the scale from 0 to 4, with 4 reflecting the very significant impact, and 0 no impact. At baseline, the impact of floaters on the daily life of the subject was assessed a week before the beginning of supplementation. After supplementation, the same questions were posed again at the final visit to assess the impact of floaters on the daily life of the subjects a week prior to the visit. An improvement for a participant was defined as a lesser score at the final visit in comparison with the score obtained during the baseline visit.

[0110] At baseline, the same median score (IQR) of 1.00 (0.00-2.00) was noted for both groups (p=0.407; Mean±SD score of assessment 1.08±0.85 and 1.37±1.27 for the control and active groups, respectively). Following supplementation, the median scores reported were 1.00 (0.00-2.00) and 0.50 (0.00-1.00) for the control and active groups (p=0.302), respectively. Within group comparisons of the baseline and final scores revealed a statistically significant difference for the active group (p=0.003) but not for the control group (p=0.658).

[0111] When asked about the impact of floaters on their daily life a week prior to the study, 7 subjects from the control group and 9 subjects from the active group reported no impact of their floaters on their daily life. Following supplementation, 10 subjects in the control group reported the lack of impact of floaters on their daily life and this difference was not statistically significant (p=0.658). Within the active group, however, 14 subjects reported no impact of floaters on their daily life post supplementation and this improvement was statistically significant (p=0.003). In summary, for the control group the results reported by the patients proved that the state of 13 subjects (50%) remained without changes, the state of 7 subjects (26.92%) improved, and the state of 6 subjects (23.08%) deteriorated in the 6-month study period. For the active group, the results reported by the patients proved that the state of 14 subjects (46.67%) remained without changes, the state of 14 subjects (46.67%) improved, and the state of 2 subjects (6.67%) deteriorated in the 6-month supplementation period between the baseline and the final visits. See Table 2 below.

TABLE-US-00002 TABLE 2 Change in the assessment of the impact of vitreous floaters on daily life in the control and active groups following 6 months of supplementation Active Group (supplemented with the Control Group composition according (placebo) to the present invention) number of tested patients number of tested patients Without 13 14 changes Improvement 7 14 Deterioration 6 2

[0112] Impact of Vitreous Floaters on Certain Activities in the Control and Active Groups After 6 Months of Supplementation

[0113] The impact of vitreous floaters on certain activities: reading small letters (drugs or cosmetics information leaflets), reading newspapers or books, driving a car during the day, using a computer or a mobile phone, watching TV was assessed before the commencement of the study at the baseline visit and after the end of the study at the final visit by subjects responding with either “Yes” or “No” to each activity. A “Yes” response for a certain activity meant disturbances caused by vitreous floaters during this activity. A positive response was scored 1, a negative 0. An overall activity score was calculated by summing up and averaging the individual activity scores reported by each participant of the study. The median overall activity score was determined for each tested group at the baseline and final visits, compared between the groups and within the groups pre and post supplementation.

[0114] At baseline, the median overall activity scores (IQR) were 0.40 (0.10-0.80) and 0.60 (0.30 0.80) for the control and active groups (p=0.104), respectively. Following supplementation, the median overall activity scores were 0.20 (0.00-0.50) and 0.20 (0.00-0.60) for the control and active groups (p=0.619), respectively. Comparing the baseline and final overall activity scores within both groups, there was a statistically significant difference (p=0.007) in median overall activity score for the active group after 6 months of supplementation, with a lesser score recorded at the final visit (where the lesser score indicates less activities affected by floaters). The difference observed in the control group was, on the other hand, not statistically significant (p=0.064).

Subjective Severity of Floater Disturbances Categorized by Age, Sex or PVD Status, Before and After Supplementation in the Active Group

[0115] To assess the influence of demographic factors on the application of the supplementation, the active group was stratified by age, sex and posterior vitreous detachment (PVD) status.

[0116] With a median age of 56.5 years, the participants of the study were divided into two age groups: 55 years and below (n=12), and beyond 55 years (n=18), and the severity of their floater disturbances in the groups were compared before and after supplementation.

[0117] Both age groups had the same median score (IQR) of 3.00 (3.00-6.00) at baseline (p=0.890) and the same median score (IQR) of 3.00 (0.00-3.00) following supplementation (p=0.787). Age did not, thus, influence the median score within the active group subjected to the supplementation.

[0118] The active group was split into males (n=13) and females (n=17), and their responses were compared. Both groups had the same median score (IQR) of 3.00 (3.00-6.00) at baseline (p=0.765) and the same median score (IQR) of 3.00 (0.00-3.00) following supplementation (p=0.755). Sex did not, thus, influence the median score within the active group following supplementation.

[0119] The patients were again divided according to their PVD status into PVD (n=12) and no PVD (n=18) subgroups, and their median scores were compared. PVD in this case referred to the subjects with complete posterior vitreous detachment, which was observed in the biomicroscopy with the aid of the optical coherent tomography (OCT) and in the slit lamp. Both subgroups had the same median score (IQR) of 3.00 (3.00-6.00) at baseline (p=0.890). Following supplementation, the median scores (IQR) reported were 0.00 (0.00-3.00) and 3.00 (1.50-3.00) for the PVD and no PVD subgroups, respectively, but the difference was not statistically significant (p=0.213).

Changes in Visual Functions in the Active and Control Groups Before and After Supplementation

[0120] The binocular contrast threshold was tested to assess the binocular contrast sensitivity pre and post supplementation, in order to assess the impact of vitreous floaters and the supplementation on the overall contrast sensitivity. It was observed for the active group that there is an improvement tendency in all conducted contrast sensitivity tests. The control group had varying results relating both to increases as well as decreases in contrast sensitivity at the end of the 6-month study period. Comparisons within groups showed statistically significant improvement on the MultiQuity LogCS scale (p=0.009) in the active group, whereas in the control group no improvement has been observed (p=0.855). A trend has also been observed towards the improvement of contrast sensitivity in the binocular contrast thresholds measured for the active group, but not for the control group. See Table 3 below.

TABLE-US-00003 TABLE 3 Comparison of the changes in visual functions in the active and control groups before and after supplementation. ACTIVE GROUP CONTROL GROUP (supplemented with the composition Visual (placebo) according to the present invention) function Baseline Final Baseline Final measures [Median (IQR)] [Median (IQR)] Sig. [Median (IQR)] [Median (IQR)] Sig. CS record  1.50  1.80 0.855  1.50  1.80 0.009* result (1.40-1.90) (1.40-1.90) (1.30-1.88) (1.45-1.90) Positive 14.97 15.18 0.551 18.55 14.94 0.053 photopic (11.73-26.38) (10.73-23.01) (10.15-29.89)  (9.87-25.02) FCS Negative 13.56 12.79 0.517 15.84 14.08 0.239 photopic  (9.46-31.56)  (9.77-18.40)  (8.87-29.55)  (9.61-24.19) FCS Positive 71.42 73.11 0.563 78.28 70.04 0.191 mesopic  (54.65-105.38) (56.07-92.02) (52.12-98.12) .sup. (43.42-100.92 FCS Negative 64.93 59.00 0.201 65.37 57.29 0.982 mesopic (46.76-81.13) (40.95-82.05) (36.34-83.59) (32.64-94.21) FCS MPOD  0.33  0.37 0.168  0.36  0.36 0.006* 0.51° (0.24-0.47) (0.24-0.47) (0.26-0.45) (0.27-0.47) MP size 5034.00  4992.00  0.150 4795.50  5296.00  0.753 (3119.50-6619)   (2971.50-6208.50) (2870.75-6266.50) (2767.25-6427.25) IQR—Interquartile range Sig.—the statistical difference between the two time points CS—Contrast Sensitivity FCS—Functional Contrast Sensitivity FCS measurements are registered as contrast threshold (%) *statistically significant difference between two time points in the range of 0.05 MPOD—Macular Pigment Optical Density MP—Macular Pigment

Assessment Questionnaire of the Quality of Life in the Patients with Vitreous Floaters

[0121] The questionnaire should be assessed by a clinician. The questionnaire is adapted to assess the functional disturbances of vitreous floaters. [0122] Name: [0123] Sex: [0124] Birthdate: [0125] Theme 1: Eyes with vitreous floaters [0126] Question: Which of your eyes has vitreous floaters: right eye, left eye or both? [0127] Tick the appropriate: [0128] a. Right eye [0129] b. Left eye [0130] c. Both eyes [0131] Skip to theme 3 if floaters are present in one eye only. [0132] Theme 2: The eye suffering from greater floater disturbances [0133] Question: Which of your eyes bothers you more: the right or the left? [0134] Tick the appropriate: [0135] a. Right eye [0136] b. Left eye [0137] Theme 3: Frequency of floater disturbances during the day [0138] Question: When during the day are the floaters most bothersome for you: in the morning, afternoon, evening or never? [0139] Assess and tick the appropriate: [0140] 0. never [0141] 1. once a day (either in the morning, or in the afternoon, or in the evening) [0142] 2. twice a day (when two times of the day are indicated) [0143] 3. all the time (when floaters appear in the morning, afternoon and evening) [0144] Score= [0145] Theme 4: Impact of vitreous floaters on daily life [0146] Question: How would you describe the impact of vitreous floaters on your daily life in the course of the past week: no impact, a small impact, a moderate impact, a significant impact, a great impact? [0147] Assess and tick the appropriate: [0148] 0. no impact [0149] 1. small impact [0150] 2. moderate impact [0151] 3. significant impact [0152] 4. great impact [0153] Score= [0154] Theme 5: Activities affected by vitreous floaters [0155] Question: Do vitreous floaters impair the below activities? [0156] Score: Yes=1, No=0 [0157] a. reading small prints (drug or cosmetics information leaflets) [0158] b. reading newspapers or books [0159] c. driving a car during the day [0160] d. using a computer or a mobile phone [0161] e. watching TV [0162] Score= [0163] Theme 6: Degree of floater disturbances in the course of the past 6 months [0164] Question: How can you describe the degree of floater disturbances in the course of the past 6 months? [0165] My condition has been stable and I have not been bothered by my floaters [0166] My floaters appear occasionally and are moderately bothersome [0167] My floaters appear all the time and are consistently bothersome [0168] Score for the floater disturbance=

CONCLUSIONS

[0169] The supplementation with the composition according to the present invention improves the subjective assessment of the quality of life of persons suffering from vitreous floaters. Simultaneously, unexpectedly for the inventors, after 6 months of conducting studies, there has been observed the significant improvement of the contrast sensitivity in the active group which received the composition of the dietary supplement according to the present invention and a lack of a relevant change in the control group which was given the placebo. The significant improvement of the contrast sensitivity in the active group which received the composition of the dietary supplement according to the present invention was statistically relevant in comparison with the group which did not receive this composition. The performance of the composition of the dietary supplement is not affected by age, sex and the presence and development stage of posterior vitreous detachment (PVD). During the 6-month supplementation period with the composition according to the present invention, persons from the active group did not report any side-effects of the studied composition.

[0170] Due to the conducted studies, the inventors unexpectedly observed that the consumption of the composition of the dietary supplement and/or nutritional additive for food according to the present invention significantly improves the subjective assessment of the quality of life in persons suffering from vitreous floaters.

[0171] Simultaneously, after the 6-month supplementation period with the composition according to the present invention, there has been observed the clearly detectable and significant improvement of the quality of visual performance in these patients through the significant improvement of the contrast sensitivity.

[0172] The present invention provides the composition of nutritional substances for oral administration, which positively impacts the quality of vision and contrast sensitivity in persons suffering from vitreous floaters.

[0173] Simultaneously, basing on the general knowledge on and experience in pathomechanisms, the course and development of various eye diseases, and the knowledge on the properties of the active substances used in the composition according to the present invention, and basing on the studies conducted for the purpose of the present invention and described above, which related to persons suffering from vitreous floaters, it is claimed that the developed composition and the unitary dosage form according to the present invention are suitable to provide a similar positive therapeutic effect and be used also in treating other different eye diseases and/or slowing down their development and/or inhibiting their development and/or preventing them, as well as, more generally, to be used with the aim to improve the quality of visual performance including contrast sensitivity in all persons in need of such an improvement, and with the aim to improve the quality of life of these persons.