Grape seed extract for use in preventing or reducing stress

Abstract

The present invention provides a pharmaceutical or nutraceutical composition based on active plant ingredients for the prevention or reduction of stress. [Solution] A grape seed extract for use in preventing or alleviating the perception of stress symptoms, in particular a grape seed extract having a proanthocyanidin content of more than 95% by weight and a catechin and epicatechin content of 5% to 15% by weight.

Description

Technical Field

[0001] The present invention relates to a pharmaceutical composition or a dietary supplement composition based on active plant ingredients for the prevention or reduction of stress.

Background Art

[0002] Generally, stress can be defined as a general syndrome of the adaptation of organisms designed to restore a new internal balance following external factors known as "stressors". Stress may involve changes in the internal balance of organisms at the endocrine, mood, organic and / or biological levels.

[0003] Generally, a type of stress involving physiological reactions and changes is defined as eustress (good stress). Conversely, a type of stress accompanied by excessive reactions is defined as distress (bad stress). Such stress may cause chronic diseases such as anxiety and depression, and psychosomatic diseases that have an adverse effect on the quality of life of patients.

[0004] Diseases caused by stress are treated with psychotherapy, dietary supplements based on natural products or synthetic drugs, and the like.

[0005] While prior art provides several, sometimes controversial, definitions of stress, in this invention, the term “stress” is used to mean pathological dysfunction caused by abnormalities in the autonomic nervous system; the system is interconnected with the central and peripheral nervous systems and is responsible for maintaining the body in a resting state by regulating the activation of the sympathetic and parasympathetic nervous systems. As a result, changes in the operation of the autonomic nervous system, such as in a stressful state, affect the central nervous system and endocrine system, while also influencing the immune response. Furthermore, stress leads to dysfunction of the sympathetic and parasympathetic nervous systems, resulting in changes in cardiac function. The changes caused by the stress can lead to cardiovascular and cerebrovascular diseases, as well as many other physical ailments such as mental disorders (International Journal of Applied Engineering Research 2018, vol. 13, no. 2, pp. 1460-1464). Grape seed extract is a well-known natural active ingredient useful in treating forms of anxiety, and has been used in the prevention and treatment of cardiovascular disorders (Film filed by GV KURANOV, RU2315616C; Belcaro G. et al., Evidence Based Complementary and Alternative Medicine, 2013, Art. ID 313142).

[0006] For example, CN108125013A (filed by DALIAN DENTBIO TECH CO LTD) describes a chewing gum containing various ingredients, including grape seed extract, that are useful in alleviating symptoms of anxiety and insomnia (among other things).

[0007] CN105918864A (filed by Hefei Guangzhou Grain Trading Co., Ltd.) discloses a fermented rice-based composition consisting of various plant-derived components including a small amount of grape seed extract, which is useful for various purposes such as improving cognitive function, increasing internal mental energy ("Tongfi"), and lowering blood pressure.

[0008] CN108936151A (filed by UNIV ANTI JIN COMMERCE) discloses a composition based on Lysium lutenicum (black goji berry) and also containing various other plant-based ingredients, including grape seed extract, for the treatment of anxiety and insomnia.

[0009] WO2016020853A (filed by Rottapharm Biotech Srl) discloses compositions based on purified cocoa extract and purified grape seed extract for the treatment of various pathological conditions, including depressive syndrome and mental weakness / atonic states. The grape seed extract contains 16-25% by weight of flavan-3-ol and more than 15% by weight of catechin + epicatechin.

[0010] WO2016020855A (filed by Rottapharm Biotech Srl) discloses grape seed extract for the treatment of various pathological conditions, including depressive syndrome, a method for preparing the same, and pharmaceutical compositions containing the extract.

[0011] WO2019046660A (filed by TALBOTT Shawn) discloses a dietary supplement containing natural extracts (a combination of pine bark, grape seed, and apple extracts, including both fruit and peel) and prebiotics which are effective in reducing bad mood.

[0012] Terauchi M. et al., Menopause: The Journal of The North American Menopause Society, 2014, Vol. 21, No. 9, pp. 990-996, reports on a study conducted in premenopausal and postmenopausal women to evaluate the effects of administering proanthocyanidin extracts from grape seeds, particularly extracts containing 85% proanthocyanidins (Gravinol®) at doses of 100 mg / day or 200 mg / day. This study revealed that "administration of the extract not only improved menopausal physical and mental symptoms, increased muscle mass, and decreased blood pressure, but also reduced anxiety according to the HADS questionnaire criteria (Zigmond AS, et al., Acta PhysiatrScand. 1983; 67; 14: 117-126)."

[0013] Vogels N., European Journal of Clinical Nutrition, (2004) 58, pp. 667-673, reports on a study conducted to evaluate the effects of administering 300 mg / day of grape seed extract containing over 90% proanthocyanidins on human food intake. The authors comment that no mood changes were observed after administration of the extract (p. 670, right column, lines 14-15 from the top of the page, "Mood and tolerance were not affected when using grape seed supplements").

[0014] Alrefaie Z., Int. J. Vitamin. Nutr. Res., 85 (5-6), 2015, 282-291 reports on a study conducted to evaluate the ancillary effects of grape seed extract in hypercholesterolemia rats. The extract was obtained by drying the seeds at 70°C for 72 hours, followed by extraction with petroleum ether.

[0015] However, none of the aforementioned documents describe the specific use of grape seed extract for the prevention or reduction of stress. [Overview of the project]

[0016] The applicant has found that by advantageously using grape seed extract, particularly an extract having a proanthocyanidin content of more than 95% by weight and a catechin and epicatechin content of 5% to 15% by weight, it is possible to prevent or reduce the perception of stress symptoms, particularly in male populations.

[0017] "Perception of stress symptoms" here refers to the worries that an individual experiences. tension, joy and demand The "Perceptual Stress Questionnaire" (PSQ20) (Fliege et al. Psychosom Med. 2005 Jan-Feb;67(1):78-88), which evaluates the sense of stress, was measured in individuals. One or more It refers to feelings. Each emotion is evaluated using five questions.

[0018] Therefore, a first aspect of the present invention relates to a grape seed extract for use in preventing or reducing the perception of stress symptoms, particularly in male populations.

[0019] In a second aspect, the present invention relates to a grape seed extract for use in preventing or reducing the perception of stress symptoms, particularly in male individuals with moderate hypertension, i.e., having an average systolic pressure in the range of 125 to 140 mmHg.

[0020] In a further aspect of the present invention, the present invention relates to a method for preventing or reducing the perception of stress symptoms, particularly in male populations, and more specifically in male individuals having moderate hypertension, i.e., an average systolic pressure in the range of 125–140 mmHg, comprising the administration of grape seed extract. [Modes for carrying out the invention]

[0021] The grape seed extract useful for the use or method of the present invention is a grape seed extract characterized by a proanthocyanidin content exceeding 95% by weight (typically measured by the Folin UV method) and a catechin and epicatechin content of 5% to 15% by weight (typically measured by HPLC).

[0022] Preferably, a grape seed extract commercially available from Indena S.p.A. of Italy under the trademark Enovita® is used, and this extract can be easily obtained by hydrothermal extraction and subsequent column chromatography on a polymer resin.

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

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

Example

[0025] Experimental section Test content The grape seed extract used was the Enovita® extract commercially available from Indena S.p.A. of Milan (IT), in tablet formulation, and each tablet contained 150 mg of the extract.

[0026] 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.

[0027]

Table 1

[0028] [Table 2]

[0029] The double-blind, randomized, placebo-controlled trial consisted of 80 subjects aged 40–70 years (35 menopausal women and 45 men) with a mean systolic pressure (measured over 7 days) in the range of 125–140 mmHg, who had not received pharmacological treatment, and whose body weight was between 19–32 kg / m². 2 The study was conducted on a non-smoking population with a BMI (Body Mass Index) within a specified range. Individuals with a polyphenol-rich diet, i.e., those who consumed five or more types of fruits and vegetables per day, were excluded from the study.

[0030] The tablets were administered twice a day for 16 weeks, immediately before breakfast and lunch (5-10 minutes prior).

[0031] The perception of stress symptoms was assessed using the Perceived Stress Questionnaire (PSQ20) (Fliege et al. Psychosom Med. 2005 Jan-Feb;67(1):78-88). This method is a well-established way to assess stress perceived by subjects independently of specific or objective circumstances. The study considers four aspects: worry, tension, pleasure, and need, each with five items. The questionnaire was completed at three different time points: on the first day of administration of grape seed extract (T-1), and then at 57 days (T-2) and 113 days (T-3) after the start of administration.

[0032] result The PSQ20 results are shown in the table below and relate to one of the aspects evaluated in each test.

[0033] [Table 3]

[0034] [Table 4]

[0035] [Table 5]

[0036] [Table 6]

[0037] The results shown in Tables 3-6 above demonstrate that while the change in the feeling of joy was not significant (p=0.6314), there was a significant decrease in the feeling of worry (p=0.00199) in the group of subjects treated with grape seed extract, and this significance was confirmed even when compared to placebo. Furthermore, a moderate decrease in the feeling of tension (p=0.6065) was observed in the treated subjects. Therefore, it can be concluded that the administration of grape seed extract reduces the perception of stress symptoms, particularly the perception of worry.

Claims

[Claim 1] A pharmaceutical composition comprising grape seed extract for use in preventing or reducing the perception of stress symptoms, The perceived stress symptom is anxiety. A pharmaceutical composition wherein the grape seed extract is an aqueous extract having a proanthocyanidin content exceeding 95% by weight as measured by the Forin UV method, and a catechin and epicatechin content of 5% to 15% by weight as measured by HPLC.

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