GRAPE SEED EXTRACTS FOR USE IN THE PREVENTION OR REDUCTION OF STRESS

Abstract

Disclosed are compositions comprising grape seed extracts, in particular extracts with a proanthocyanidin content exceeding 95% by weight and a catechin and epicatechin content ≥5% and ≤15% by weight, which are useful to prevent or reduce the perception of stress symptoms, in particular the perception of stress among the male population.

Claims

1. A method of preventing or reducing perception of stress symptoms in subjects in need thereof, said method comprising administering to said subjects a pharmaceutical effective amount of grape seed extracts.

2. The method according to claim 1, said extracts having a proanthocyanidin content greater than 95% by weight and a catechin and epicatechin content ≥5% and ≤15% by weight.

3. The method according to claim 1, wherein said subjects belong to the male population.

4. A method of preventing or reducing feelings of worry or tension in subjects in need thereof, said method comprising, administering to said subjects a pharmaceutical effective amounts of grape seed extracts.

5. A method of preventing or reducing feelings of worry in subjects in need thereof, said method comprising, administering to said subjects a pharmaceutical effective amounts of grape seed extracts.

6. The method according to claim 1, wherein said pharmaceutical effective amount of grape seed extracts comprises 150 mg of extracts twice a day.

7. The method according to claim 1, wherein said pharmaceutical effective amount of grape seed extracts is administered orally.

8. The method according to claim 4, said extracts having a proanthocyanidin content greater than 95% by weight and a catechin and epicatechin content ≥5% and ≤15% by weight.

9. The method according to claim 4, wherein said subjects belong to the male population.

10. The method according to claim 4, wherein said pharmaceutical effective amount of grape seed extracts comprises 150 mg of extracts twice a day.

11. The method according to claim 4, wherein said pharmaceutical effective amount of grape seed extracts is administered orally.

Description

DESCRIPTION OF THE INVENTION

[0016] The Applicant has now discovered that grape seed extracts, in particular extracts having a proanthocyanidin content exceeding 95% by weight and a catechin and epicatechin content ≥5% and ≤15% by weight, can be advantageously used to prevent or reduce the perception of stress symptoms, in particular the perception of stress symptoms among the male population.

[0017] “Perception of stress symptoms” here means one or more of the feelings measured in an individual using the “Perceived Stress Questionnaire” (PSQ20) (Fliege et al. Psychosom Med. 2005 January-February; 67(1):78-88), which evaluates the feelings of worry, tension, joy and demands experienced by an individual. Each feeling is evaluated with five questions.

[0018] Thus in a first aspect thereof, the invention relates to grape seed extracts for use in preventing or reducing the perception of stress symptoms, in particular among the male population.

[0019] In a second aspect thereof, the invention relates to grape seed extracts for use in preventing or reducing the perception of stress symptoms, in particular in male individuals with moderate hypertension, i.e. with mean systolic pressure values ranging from 125 to 140 mmHg.

[0020] In a further aspect thereof, the invention relates to a method for preventing or reducing the perception of stress symptoms, in particular among the male population, and more particularly among male individuals with moderate hypertension, i.e. with mean systolic pressure values ranging from 125 to 140 mmHg, comprising the administration of grape seed extracts.

[0021] The grape seed extracts useful for the use or method according to the invention are grape seed extracts characterised by a proanthocyanidin content (typically measured by the Folin UV method) exceeding 95% by weight, and a catechin and epicatechin content ≥5% and ≤15% by weight (typically measured by HPLC).

[0022] A grape seed extract commercially available from Indena S.p.A., Italy, under the trademark Enovita™ is preferably used; said extract can be conveniently obtained by extraction under heating with water and subsequent column chromatography on polymer resin.

[0023] The extracts can be administered orally at the dose of 150 mg twice a day, preferably before breakfast and before lunch. The extracts can be formulated by techniques known to the skilled person for the preparation of liquid or solid pharmaceutical foul's, using known excipients suitable for said purpose. Said formulations and excipients are described, for example, in Remington, “The Science and Practice of Pharmacy”, 22.sup.nd edition, Pharmaceutical Press, 2013. The extracts can preferably be formulated as tablets, each containing 150 mg of extract.

[0024] The invention is described in detail in the experimental section below.

[0025] Experimental Section

[0026] Description of Study

[0027] The grape seed extract used was Enovita.sup.TM extract, commercially available from Indena S.p.A., Milan (IT), in tablet foimulation, each tablet containing 150 mg of extract.

[0028] Table 1 shows the composition of the tablets containing the extract, while Table 2 shows the composition of the placebo tablets used in the study

TABLE-US-00001 TABLE 1 INGREDIENT mg/tablet Grape seeds, dried extract 150.0 mg  ENOVITA ® Anhydrous dibasic calcium phosphate 190.0 mg  Di-cafos ® A150 E341(ii) Microcrystalline cellulose 302 147.0 mg  Polyvinylpolypyrrolidone 27.0 mg Polyplasdone ® XL E1202 Crosslinked sodium 15.0 mg carboxymethylcellulose Silicon dioxide 11.0 mg (Syloid ® 244 FP) Magnesium stearate  5.0 mg Talc  5.0 mg Film-coating agent 30.0 mg Opadry ® white and purple Hydroxypropyl methylcellulose Titanium dioxide Polydextrose Talc Maltodextrin Medium-chain triglycerides Cochineal

TABLE-US-00002 TABLE 2 INGREDIENT mg/tablet Anhydrous dibasic calcium phosphate 245.0 mg  Di-cafos ® A150 E341(ii) Microcrystalline cellulose 302 362.0 mg  Silicon dioxide 13.0 mg Syloid ® 244 FP Magnesium stearate 15.0 mg Talc 15.0 mg Film-coating agent 30.0 mg Opadry ® white and purple Hydroxypropyl methylcellulose Titanium dioxide Polydextrose Talc Maltodextrin Medium-chain triglycerides Cochineal

[0029] The double-blind, randomised, placebo-controlled study was conducted on a population of non-smokers consisting of 80 subjects, 35 menopausal women and 45 men, aged between 40 and 70 years, having a mean systolic pressure (measured for a period of seven days) ranging between 125 and 140 mmHg but not receiving any pharmacological treatment, and having a BMI (body mass index) ranging between 19 and 32 kg/m.sup.2. Individuals with a diet rich in polyphenols, i.e. those with an intake of five or more portions of fruit and vegetables a day, were excluded from the study.

[0030] The tablets were administered twice a day, shortly before (5-10 minutes before) breakfast and lunch for a period of sixteen weeks.

[0031] The perception of stress symptoms was evaluated with the “Perceived Stress Questionnaire” (PSQ20) (Fliege et al. Psychosom Med. 2005 January-February; 67(1):78-88), a well-established method that evaluates the stress perceived by a subject independently of a specific or objective situation. The test considers four aspects: worry, tension, joy and demands, each with five items. The questionnaire was completed at three different times, on the first day of administration of the grape seed extract (T-1), then 57 (fifty-seven) days (T-2) and 113 (one hundred and thirteen) days (T3) after the start of administration.

[0032] Results

[0033] The results of PSQ20 are set out in the tables below, each relating to one of the aspects evaluated in the test.

TABLE-US-00003 TABLE 3 Grape seed Grape seed Grape seed Placebo tablets Placebo tablets Placebo tablets extract tablets extract tablets extract tablets Feeling of worry T1 T2 T3 T1 T2 T3 Number of values 38 38 38 40 40 40 Minimum 0 0 0 0 0 0 25th percentile 0 0 0 6.67 0 0 Median 20 10 20 13.33 13.33 6.67 75 th percentile 28.34 28.34 33.33 26.67 20 20 Maximum 53.33 53.33 60 60 60 53.33 Mean 17.9 14.9 18.4 16.5 14.7 13.7 Std Deviation 14.5 15.5 16.3 14.9 14.6 16.0 Std Error 2.3 2.5 2.6 2.4 2.3 2.5 Lower limit of 95% 13.1 9.8 13.1 11.7 10.0 8.6 confidence interval Upper limit of 95% 22.7 20.0 23.8 21.3 19.3 18.8 confidence interval

TABLE-US-00004 TABLE 4 Grape seed Grape seed Grape seed Placebo tablets Placebo tablets Placebo tablets extract tablets extract tablets extract tablets Tension T1 T2 T3 T1 T2 T3 Number of values 38 38 38 40 40 40 Minimum 0 0 0 0 0 0 25th percentile 13.33 6.67 6.67 8.335 6.67 1.668 Median 26.67 23.34 20 20 20 20 75 th percentile 35 40 40 33.33 33.33 33.33 Maximum 66.67 60 66.67 66.67 73.33 86.67 Mean 26.5 24.7 25.3 21.3 21.5 20.3 Std Deviation 16.1 17.6 19.9 17.2 17.0 18.7 Std Error 2.6 2.9 3.2 2.7 2.7 3.0 Lower limit of 95% 21.2 19.0 18.7 15.8 16.1 14.3 confidence interval Upper limit of 95% 31.8 30.5 31.8 26.8 26.9 26.3 confidence interval

TABLE-US-00005 TABLE 5 Placebo tablets Placebo tablets Placebo tablets Grape seed extract Grape seed extract Grape seed extract Joy T1 T2 T3 tablets T1 tablets T2 tablets T3 Number of values 38 38 38 40 40 40 Minimum 26.67 33.33 26.67 40 26.67 33.33 25th percentile 65 58.33 60 60 61.67 60 Median 73.33 73.33 73.33 73.33 73.33 73.33 75 th percentile 86.67 86.67 88.34 86.67 86.67 86.67 Maximum 100 100 100 100 100 100 Mean 71.6 72.5 71.4 73.2 72.8 74.3 Std Deviation 18.4 18.7 20.9 16.8 19.2 17.8 Std Error 3.0 3.0 3.4 2.7 3.0 2.8 Lower limit of 95% 65.5 66.3 64.6 67.8 66.7 68.6 confidence interval Upper limit of 95% 77.6 78.6 78.3 78.6 79.0 80.0 confidence interval

TABLE-US-00006 TABLE 6 Grape seed Grape seed Grape seed Placebo tablets Placebo Tablets Placebo Tablets extract tablets extract tablets extract tablets Demands T1 T2 T3 T1 T2 T3 Number of values 38 38 38 40 40 40 Minimum 0 0 0 0 0 0 25 th percentile 20 13.33 20 13.33 20 8.335 Median 33.33 30 20 30 26.67 26.67 75th percentile 53.33 46.67 46.67 46.67 46.67 33.33 Maximum 66.67 73.33 80 66.67 80 66.67 Mean 35.1 31.4 30.7 28.3 29.5 26.5 Std Deviation 18.6 20.2 21.8 19.1 18.1 18.8 Std Error 3.0 3.3 3.5 3.0 2.9 3.0 Lower limit of 95% 29.0 24.8 23.5 22.2 23.7 20.5 confidence interval Upper limit of 95% 41.2 38.0 37.9 34.4 35.3 32.5 confidence interval

[0034] The results set out in Tables 3-6 above demonstrate that while the variation in the feeling of joy was not significant (p=0.6314), there was a significant reduction (p=0.00199) in the feeling of worry in the group of subjects treated with grape seed extract, and said significance was also confirmed in the comparison with the placebo; moreover, a moderate reduction in the feeling of tension (p=0.6065) was observed in the treated subjects. It can therefore be concluded that administration of the grape seed extract reduces the perception of stress symptoms, in particular the perception of the feeling of worry.