Herbal composition for treating or preventing postpartum depression

Abstract

The present invention relates to a composition comprising the following as active ingredients: a dry extract of solanum nigrum, a dry extract of melissa, a microencapsulated essential oil of lavandula angustifolia, and optionally vitamin D3, for use in the prevention and / or treatment of postpartum depression (PPD).

Description

Technical Field

[0001] The composition of the present invention belongs to the technical field of a composition or combination of active ingredients that can be used to treat postpartum depression. Background Art

[0002] After childbirth, a major depressive disorder called postpartum depression affects approximately 8%-12% of new mothers. One of the most common medical complications of the postpartum period, postpartum depression (PPD) includes major and minor depressive episodes that occur during pregnancy or in the first 12 months after childbirth, affecting one in seven women. PPD can have a devastating impact on women, children, and families; maternal suicide surpasses bleeding and hypertensive disorders as a cause of maternal mortality.

[0003] Compared with depression occurring outside the postpartum period, there is currently little research on PPD, although there has been some discussion in the recent scientific literature about the definition of this condition and, more specifically, the differences between PPD and depression occurring outside the postpartum period.

[0004] Di Florio et al. (Di Florio A, Meltzer-Brody S., "Is Postpartum Depression a Distinct Disorder?". Curr Psychiatry Rep. 2015 Oct; 17(10): 76) highlighted the reasons why postpartum depression (PPD) should be considered a pathology different from depression. In particular, the reasons supporting the distinction between the two pathologies are: 1) guide : There are specific guidelines for postpartum depression (e.g. NICE and SIGN guidelines) because the identification and treatment of women with PPD requires specific considerations that do not generally apply to depression outside the perinatal period. In addition, the treatment needs of women with PPD differ from those of women with normal depression and often require a multidisciplinary approach (doctors need to consider the effects of psychotropic medications during breastfeeding and recognize and treat the mother in the context of her relationship with her child). 2) Prognosis and outcome: Some epidemiological and clinical studies have shown an association between bipolar diathesis and PPD; therefore, evidence of a link between childbirth and bipolar disorder has led doctors to use particular caution when assessing, treating, and following up women with PPD because they are at increased risk of developing bipolar diathesis. This characteristic also distinguishes women with PPD from women with depression outside the perinatal period. 3) Genetic factors: Studies have shown that there are genetic differences between women with PPD and women with depression other than perinatal depression. Therefore, it is plausible that these two pathologies require different treatments and clinical interventions and this strengthens the idea of ​​considering these two pathologies as different pathologies. 4) Epidemiology : Many epidemiological and clinical studies have shown that depression is more common after childbirth than at other times in a woman's life, suggesting an etiological link precisely to this specific moment in a woman's life.

[0005] Batt et al. (Melissa M Batt et al., "Is Postpartum Depression Different From Depression Occurring Outside of the Perinatal Period? A Review of the Evidence". Focus (Am Psychiatr Publ) 2020Apr; 18(2): 106-119) emphasizes the similarities and differences between PPD and depression outside the perinatal period. In particular, it points out that if the period up to 8 weeks after the birth of the child is considered the postpartum period, the difference between the two types of depression is very obvious, because within this time frame, the severity of symptoms, hormone levels, genetics, epigenetic data, and response to treatment are different from those of the postpartum period after 8 weeks, and the severity of symptoms, hormone levels, genetics, epigenetic data, and response to treatment of the postpartum period after 8 weeks are more similar to those of depression occurring outside the perinatal period.

[0006] Furthermore, with respect to treatment, it has been suggested that treatment of early-stage PPD may be beneficial compared to late-stage PPD, which instead responds to treatment like normal depression.

[0007] According to the NICE guidelines (Antenatal and postnatal mental health: clinical management and service guidance. www.nice.org.uk / guidance / cg192 ), the management of PPD differs from other depressions because of the specific nature of this period of a woman's life and also because of the potential impact that this type of depression can have not only on the woman but also on the child. The publication also highlights the fact that there are no psychotropics approved for postpartum depression in Europe; therefore, the attending physician must assume the responsibility of prescribing psychotropics during this very vulnerable period of a woman's life. In fact, psychotropics cannot be used during breastfeeding and they can alter a woman's ability to care for her baby (e.g., sedatives).

[0008] Comparative studies have also been conducted to compare the symptomatology and biological responses of patients with normal depression and those with PPD or PPD-like conditions.

[0009] A retrospective study comparing symptoms and responses to treatment in 26 women with PPD and 25 women with normal depression noted:

[0010] -Women with PPD experience more intense anxiety and more severe depression than women with normal depression;

[0011] - Response time to pharmacotherapy was longer in women with PPD than in women with normal depression (6 weeks vs 3 weeks);

[0012] - When a pharmacotherapy response was achieved, 60% of women with PPD were treated not with a single depressant medication, but with multiple depressant medications (compared to 4% of women with normal depression).

[0013] Thus, the authors concluded that there are clear differences between PPD and normal depression: in fact, women with PPD have more pronounced anxious features, take longer to respond to antidepressants and require more antidepressant use to achieve a response to treatment (Hendrick V et al., "Postpartum and nonpostpartum depression: differences in presentation and response to pharmacologic treatment". Depress Anxiety 2000; 11(2): 66-72).

[0014] O'Brien et al. (O'Brien S et al., "Is postnatal depression a distinct subtype of major depressive disorder? An exploratory study". Arch Womens Ment Health. 2021Apr; 24(2): 329-333) conducted an exploratory study to test whether women with a history of PPD have specific differences in brain activation compared to women with normal depression. This test was done by performing functional magnetic resonance imaging (fMRI) scans on the recruited women, which measured brain activation at the level of the amygdala (a nuclear complex in the temporal lobe of the brain that regulates emotions).

[0015] This study builds on the findings of two previous studies: The first study (Groenewold et al., 2013) observed that women with a prior history of depression (non-PPD) undergoing fMRI experienced increased activation of the amygdala when exposed to negative facial expressions. The second study (Moses-Kolko et al., 2010) conversely observed that women with PPD experienced decreased activation of the amygdala when exposed to negative facial expressions.

[0016] The aim of the study by O'Brien et al. was to make a direct comparison between women with a history of normal depression and women with a history of PPD (compared to controls). It has also been shown that a key factor in the development of PPD is the sudden decrease in sex hormones that occurs after childbirth; in fact, women who are prone to PPD are particularly sensitive to these changes. This is why measurements were taken in the late luteal phase of the menstrual cycle in the exploratory study by O'Brien et al., because the sudden decrease in estradiol and plasma progesterone concentrations during this period is somewhat similar to the postpartum hormonal environment. In this way, it is possible to evaluate how brain activation changes in women with PPD and women with normal depression, in the context of a hormonal state that simulates the postpartum period.

[0017] O'Brien et al.'s study showed that women with a history of PPD had reduced brain activity in the amygdala compared to women with a past history of normal depression. Therefore, it is speculated that there is a different brain activation in women who develop PPD compared to women who develop normal depression, which supports the idea that the two pathologies are different from each other.

[0018] Problems with the Background Art

[0019] Although many are aware of the existence of PPD, little is known about the pharmacological management of patients, who are sometimes treated with the same therapies used to treat major depressive disorder occurring outside the postpartum period.

[0020] This strategy is inadequate because of the need to avoid treatments that may harm the child either directly (through exposure to drug therapy through breastfeeding) or indirectly (because the mother's mood and resources may be altered by current drug therapy).

[0021] As highlighted by the NICE guidelines, there are currently no psychotropics approved for postpartum depression in Europe, placing the attending physician in the position of having to assess on a case-by-case basis which therapy to prescribe to treat the mother and minimise the impact that the mother may also have on the child.

[0022] It is because of this difference in clinical practice and because of the different symptom presentation from normal depression: mothers with PPD tend to have lower quality interactions with their children, including greater detachment and less positive emotions with their offspring, than mothers without depression that PPD should be considered a separate pathology. These aspects of PPD affect maternal behavior and satisfaction with the mother role; as well as affecting children in terms of ensuring optimal evolutionary outcomes. PPD is indeed associated with deficits in cognitive and socioemotional development in children, and evidence suggests that the quality of mother-child interactions affects the outcomes of such development (Melissa M Batt et al. "Is Postpartum Depression Different From Depression Occurring Outside of the Perinatal Period? A Review of the Evidence". Focus (Am Psychiatr Publ) 2020 Apr; 18(2): 106-119).

[0023] Therefore, there is a need for natural products that can be used without problems during the postpartum period and breastfeeding.

[0024] In the prior art, there are natural remedies that can be used to treat anxiety disorders or conditions attributed to depressive forms; however, in the prior art, these are not applicable to the prevention and / or treatment of postpartum depression.

[0025] EP 1796702 describes the use of lavender oil (Lavandula angustifolia;

[0009] ) for the treatment of patients suffering from somatization disorder and post-traumatic stress syndrome (PTSD; paragraph

[0011] ). The daily dose to be administered is comprised between 10 mg and 2 g, preferably between 50 mg and 100 mg (paragraph

[0017] ).

[0026] WO 2011 / 098394 describes compositions for the treatment and prevention of neurological and sleep disorders comprising extracts / tinctures of the following plants: Lavandula angustifolia (lavender), Humulus lupulus (hops), Melissa officinalis (Melissa), Passiflora incarnata (passionflower) and Valeriana officinalis (valerian) (page 1, paragraphs 12-13). Neurological disorders are defined in this document as symptoms characterized by increased excitability, irritability, sleep disturbances, insomnia, resignation, depressive detuning, decreased libido, exhaustion, anxiety, nervousness, menopausal disorders, shortness of breath, headaches, migraines, muscle contractions or twitches, heart problems (irregular heartbeat, heart pain), stomach, intestinal or bladder spasms (page 2, paragraph 3).

[0027] WO 2007 / 014334 describes a medicinal, veterinary or nutritional product comprising an extract of Withania somnifera in a concentration comprised between 0.05% and 99% by weight. The composition may also comprise other active ingredients, such as antioxidants, vitamins, minerals or plant extracts (page 6, lines 1-3). The composition is used to treat stress disorders characterized by a symptomology comprising: insomnia, palpitations, sweating, fatigue, irritability, feelings of inescapability / imminence (claim 10).

[0028] WO 2020 / 144591 describes a Withania delivery system, in particular a solid dosage form, comprising: a core comprising a layer of a Withania extract comprising solid particles (preferably composed of sugars or derivatives; page 6, lines 9-11) and covering the particles; a layer located above the core whose function is to protect the Withania from gastric juice (page 2, lines 19-25). The composition has several biological activities: immunomodulation, reduction of depressive states or anxiety, improvement of sleep disorders, improvement of male testosterone levels and duration of sexual ability. Compositions intended for the treatment of depression, anxiety, and sleep disorders are administered to subjects suffering from these conditions at doses comprised between 10 mg and 2000 mg (page 6, line 27 - page 7, line 6). Summary of the invention

[0029] Applicants have now identified a composition useful for the prevention and treatment of postpartum depression which solves the problems of the prior art.

[0030] The composition contains the following as active ingredients:

[0031] - dry extract of Withania somnifera,

[0032] - dry extract of lemon balm, and

[0033] -Microencapsulated essential oil of Lavandula angustifolia.

[0034] According to a particularly preferred embodiment, the composition may further comprise vitamin D3.

[0035] Advantages of the invention

[0036] The composition developed by the applicant is advantageous because:

[0037] -It is a natural product and safe for use by pregnant or breastfeeding women;

[0038] - It constitutes a treatment specifically for postpartum depression, thereby providing patients and physicians with a specific treatment option for PPD that currently does not exist;

[0039] - It can be taken alone or as an adjuvant to classic antidepressant or antianxiety drug therapy, allowing to reduce the number of traditional drug treatments. As shown in the literature, in fact, 60% of women with PPD use more antidepressant drugs for treatment compared to 4% of women with normal depression (Hendrick V et al., "Postpartum and nonpostpartum depression: differences in presentation and response topharmacologic treatment". Depress Anxiety 2000; 11 (2): 66-72). BRIEF DESCRIPTION OF THE DRAWINGS

[0040] Figure 1 : A bar graph showing the sum of the mean scores recorded for each of the 10 items of the EPDS questionnaire. When the score is >12.5, the woman defines herself as having PPD.

[0041] Figure 2A-2B : A bar graph showing the mean score recorded for each of the 10 items of the EPDS questionnaire. DETAILED DESCRIPTION

[0042] Composition

[0043] As intended in the Summary of the Invention, the composition to be protected comprises as active ingredient,

[0044] - dry extract of Withania somnifera,

[0045] - dry extract of lemon balm, and

[0046] -Microencapsulated essential oil of Lavandula angustifolia.

[0047] The dry extract of Withania somnifera, the dry extract of Melissa officinalis, and the microencapsulated essential oil of Lavandula angustifolia are also referred to herein as "herbs" or "herbal active ingredients" because they are plant-derived active ingredients.

[0048] According to a preferred embodiment, the dry extract of Withania somnifera, the dry extract of Melissa officinalis and the microencapsulated essential oil of Lavandula angustifolia constitute the only herbal active ingredients that are the subject of the composition of the present invention.

[0049] Although the applicant currently has no supporting experimental evidence, he believes that the combination of a dry extract of Withania somnifera, a dry extract of Melissa officinalis, and a microencapsulated essential oil of Lavandula angustifolia may be synergistic in preventing and treating postpartum depression and in preventing and treating symptoms associated therewith.

[0050] Preferably, the composition does not comprise: Hawthorn, such as, for example, Crataegus pinnatifida or Crataegus Oxyacantha, or extracts / derivatives thereof; Lavender (Lavandula officinalis) or extracts / derivatives thereof; Hops (Humuls lupulus) or extracts / derivatives thereof; Valerian (Valeriana officinalis) or extracts / derivatives thereof; Cinnamomum cassia or extracts / derivatives thereof; fruits of the genus Citrus, such as Citrus bergamia, Citrus Union, Citrus paradisi, or extracts / derivatives thereof.

[0051] Withania somnifera (Ashwagandha) has been used in medicine since Ayurveda, the ancient Indian medical system. Withania somnifera is used as an aphrodisiac, liver tonic, anti-inflammatory, astringent, and for the treatment of bronchitis, asthma, ulcers, emaciation, insomnia, and Alzheimer's disease. More recently, W. somnifera has also been shown to be useful for the treatment of anxiety, cognitive and neurological disorders, inflammation, and Parkinson's disease (Singh, G & Sharma, PK & Dudhe, Rupesh & Singh, Sukhdev. (2009). Biological activities of Withania somnifera. Ann Biol Res. 1).

[0052] For the purposes of the present invention, the dry extract of Withania somnifera is preferably an extract of the root of the plant. Furthermore, the extract of Withania somnifera is preferably characterized by ≥5 wt% of thiols in total withanolides, based on the total weight of the extract; and <0.1 wt% of titre in withaferin A, based on the total weight of the extract.

[0053] Melissa officinalis is a medicinal plant that has long been used in several ethnomedical methods, especially in traditional medicine for the treatment of several diseases (health syndromes, including neurological health syndromes, central nervous system health syndromes, cardiovascular health syndromes); as an antimicrobial agent, antidepressant and as a memory enhancer for subjects with dementia (Javad Sharifi-Rad et al. "Phytochemical Constituents, Biological Activities, and Health-Promoting Effects of the Melissa officinalis", Oxidative Medicine and Cellular Longevity, vol. 2021, Article ID 6584693, 20 pages, 2021. https: / / doi.org / 10.1155 / 2021 / 6584693 ).

[0054] For the purposes of the present invention, the dry extract of Melissa officinalis is preferably an extract of the leaves of this plant, preferably characterized by an extract / drug ratio comprised between 1:4 and 1:6. Furthermore, the dry extract of Melissa officinalis is preferably characterized by ≥12% by weight of thiols in rosmarinic acid, based on the total weight of the extract.

[0055] Lavender essential oil is used in a wide range of products, both for cosmetic and therapeutic applications; oils from a variety of lavender species have been shown to have a variety of biological activities. As an aromatic and medicinal herb, L. angustifolia is well known and appreciated by the cosmetic, food and pharmaceutical industries. Lavender essential oil is widely sold as an over-the-counter phytotherapy for the treatment of depression, anxiety and stress. International organizations including the World Health Organization (WHO), the European Medicines Agency (EMA) and the European Scientific Cooperative on Phytotherapy (ESCOP) consider lavender to be a drug approved for the relief of anxiety, stress and restlessness.

[0056] For the purposes of the present invention, lavender essential oil is preferably an extract of the flowers of Lavandula angustifolia.

[0057] The oil is in a microencapsulated form, wherein microencapsulation refers to a delivery technique in which the active ingredient is included in a particle structure having an exterior that is suitable for maintaining the biological properties, functional properties, and physicochemical properties of the core material. The microencapsulation of essential oils is well known to those skilled in the art and can be achieved with different methods, such as, for example, emulsification, spray drying, coaxial electrospraying, freeze drying, coagulation, in-situ polymerization, melt extrusion, supercritical fluid technology, and fluidized bed coating. Coagulation and spray drying are the most commonly used techniques for the microencapsulation of essential oils.

[0058] According to a preferred embodiment, the microcapsules of essential oil of Lavandula angustifolia contain between about 80% and 90% by weight of essential oil, preferably between about 85% and 90% by weight of essential oil. Preferably, the microcapsules of essential oil of Lavandula angustifolia are characterized by a particle size comprised between about 100 μm and 600 μm (more precisely, 80% of the particle population of a sample of microencapsulated essential oil of Lavandula angustifolia has a particle size determined by dynamic light scattering comprised between 100 μm and 600 μm).

[0059] Also preferably, the essential oil of Lavandula angustifolia contained in the microcapsules is characterized by a titre in linalool comprised between about 30% and 40% by weight, based on the total weight of the oil; a titre in linalool acetate comprised between about 30% and 40% by weight, based on the total weight of the oil; a titre in linalyl acetate comprised between about 30% and 40% by weight, based on the total weight of the oil.

[0060] Preferably, the dry extract of Withania somnifera is contained in the composition in a concentration comprised between about 30 and 40 wt.-%, preferably between about 32 and 38 wt.-%, preferably between about 35 and 38 wt.-%, based on the total weight of the composition.

[0061] Preferably, the dry extract of Melissa officinalis is contained in the composition in a concentration comprised between about 20% and 30% by weight, preferably between about 22% and 27% by weight, preferably between about 23% and 26% by weight, based on the total weight of the composition.

[0062] Preferably, the microencapsulated essential oil of Lavandula angustifolia is contained in the composition in a concentration comprised between about 20% and 30% by weight, preferably between about 22% and 27% by weight, preferably between about 23% and 26% by weight, based on the total weight of the composition.

[0063] According to a preferred embodiment, the administration unit of the composition comprises:

[0064] - dry extract of Withania somnifera, with a concentration comprised between 30% and 40% (w / w) and preferably with a titer in withanolides ≥ 5%;

[0065] - a dry extract of Melissa officinalis, at a concentration comprised between 20% and 30% (w / w), and preferably with a titer of rosmarinic acid ≥ 12%; and

[0066] - Microencapsulated essential oil of Lavandula angustifolia in a concentration comprised between 20% and 30% (w / w), wherein the essential oil is preferably characterized by a titer in linalool comprised between 30% and 40%.

[0067] According to a particularly preferred embodiment, the composition comprises Vitamin D3 as a further (non-herbal) active ingredient.

[0068] Preferably, a dosing unit of the composition comprises vitamin D3 in a concentration comprised between 3% and 8% by weight, based on the total weight of the composition.

[0069] Note that preferably, vitamin D3 is the only vitamin present in the composition of the present invention.

[0070] The advantages derived from the combination of vitamin D3 with the previously mentioned and described active ingredients derive from the fact that the scientific literature shows a direct correlation between vitamin D deficiency and the onset or progression of postpartum depression (Fallah M et al., "Is Vitamin D Status Associated with Depression, Anxiety and Sleep Quality in Pregnancy: A Systematic Review." Adv Biomed Res. 2020 Jul 27; 9:32; Murphy PK et al. (Murphy PK et al., "An exploratory study of postpartum depression and vitamin d." J Am Psychiatr Nurses Assoc 2010; 16: 170 7; Gur EB et al., "Mid pregnancy vitamin D levels and postpartum depression." Eur J Obstet Gynecol Reprod Biol 2014; 179: 110 6; Robinson M et al., "Low maternal serum vitamin D during pregnancy and the risk for postpartum depression symptoms." Arch Womens Ment Health 2014;17:2139; Fu CW et al., “Association between serum 25 hydroxyvitamin D levels measured24 hours after delivery and postpartum depression.” BJOG 2015;122:1688 94.).

[0071] Of particular interest is the study by Amini et al. (Amini S et al., "The effect of vitamin D and calcium supplementation on inflammatory biomarkers, estradiol levels and severity of symptoms in women with postpartum depression: A randomized double-blind clinical trial." Nutr Neurosci 2022; 25(1): 22-32.), which investigated the effects of vitamin D and calcium on the severity of symptoms and inflammatory biomarkers associated with PPD. In the study (randomized double-blind), 27 women were enrolled and divided into 3 groups (ratio 1:1:1):

[0072] -Group 1: Vitamin D + 500mg of calcium

[0073] - Group 2: Vitamin D + calcium placebo

[0074] - Group 3: Vitamin D placebo + calcium placebo (control).

[0075] Treatment lasted for 8 weeks, at which point vitamin D levels and EPDS scores were compared relative to baseline. It can be seen that there was a greater reduction in EPDS questionnaire scores relative to baseline in the group treated with (vitamin D + calcium) and the group treated with (vitamin D + calcium placebo) compared to the control group treated with placebo alone; in addition, the effect of vitamin D on EPDS scores was greater in the group treated with vitamin D alone without calcium addition. The authors therefore concluded that vitamin D can effectively improve the clinical symptoms of PPD.

[0076] According to a preferred embodiment, the administration unit of the composition comprises:

[0077] - dry extract of Withania somnifera, with a concentration comprised between 30% and 40% (w / w) and preferably with a titer in withanolides ≥ 5%;

[0078] - a dry extract of Melissa officinalis, in a concentration comprised between 20% and 30% (w / w), and preferably with a rosmarinic acid titer ≥ 12%;

[0079] - microencapsulated essential oil of Lavandula angustifolia in a concentration comprised between 20% and 30% (w / w), wherein the essential oil is preferably characterized by a titer in linalool of between 30% and 40%; and

[0080] - Vitamin D3 in a concentration comprised between 3% and 8% (w / w).

[0081] Preferably, the composition of the present invention further comprises suitable excipients and / or diluents, which can be used to formulate products intended for oral ingestion. For example, excipients and / or diluents can be selected from anti-aggregating agents (e.g., microcrystalline cellulose), bulking agents, anti-caking agents, or flow agents (e.g., silicon dioxide), emulsifiers, glidants (e.g., magnesium salts of fatty acids), stabilizers, dyes, flavoring agents.

[0082] According to a preferred embodiment of the present invention, the dry extract of Withania somnifera, the dry extract of Melissa officinalis, the microencapsulated essential oil of Lavandula angustifolia and Vitamin D3 constitute the only active ingredients that are the subject of the composition of the present invention.

[0083] Administration form of the composition

[0084] Preferably, the compositions of the invention are intended for oral administration.

[0085] Preferably, the composition of the invention is characterized in that the daily dosage is 1 or 2 dosing units.

[0086] Preferably, the composition, ie the dosing unit of the composition, is in solid or liquid form, preferably solid.

[0087] Also preferably, the composition, ie the administration unit of the composition, is in the form of a solid tablet, capsule or powder / granule.

[0088] Note that, preferably, when the composition is in the form of powder / granules, the powder / granules are dissolved in water before administration; or absorbed orally.

[0089] According to a preferred embodiment, the composition of the invention is a food supplement.

[0090] Food supplements are preparations that fall within the definition under Directive 2002 / 46 / EC, as amended. In this regulation, food supplements are precisely defined as: "foods intended to supplement the normal diet and which are concentrated sources of nutrients such as vitamins and minerals, or other substances with nutritional or physiological effects, in particular but not limited to amino acids, essential fatty acids, fibers of plant origin and extracts, both as single compounds and as a plurality of compounds, in a predetermined dosage form".

[0091] Medical Uses

[0092] As emphasized in the Summary of the Invention, the disclosed compositions are intended for the prevention and treatment of postpartum depression (PPD).

[0093] According to a preferred embodiment, the composition is used as an adjuvant to drug therapy. Note that treatment of PPD can vary according to the subject and generally includes psychological intervention (psychotherapy), and / or the use of neuroactive drugs (sedatives, anxiolytics, mood regulators, antidepressants) with all appropriate precautions, and / or the use of natural therapeutic substances (such as, for example, Hypericum, which represents a substance used for PPD, but is not without side effects).

[0094] Note that in most cases, PPD occurs in postpartum women between 4 and 6 weeks after delivery (Melissa MBatt et al. “Is Postpartum Depression Different From Depression Occurring Outside of the Perinatal Period? A Review of the Evidence”. Focus (Am Psychiatr Publ) 2020 Apr; 18(2): 106-119; Clare CA, Yeh J. Postpartum depression in special populations: a review. Obstet Gynecol Surv. 2012 May; 67(5): 313-23. doi: 10.1097 / OGX.0b013e318259cb52. PMID: 22624779).

[0095] Note that, preferably, the composition is suitable for the prevention of PPD in the following populations:

[0096] - pregnant women, preferably between the 35th and 40th week of pregnancy, or

[0097] - A postpartum woman in the neonatal period comprised between 0 and 6 weeks, preferably between 2 and 6 weeks, preferably between 2 and 4 weeks after delivery.

[0098] According to a preferred embodiment, the composition may be taken by pregnant women during the last weeks of pregnancy and may also be used for maintenance treatment during the postpartum period (also known as the neonatal period).

[0099] Preferably, the composition can be used for the treatment of PPD in postpartum women. In addition, the composition can be used to treat postpartum women in the neonatal period included between 0 weeks and 24 months, preferably included between 0 weeks and 18 months, preferably included between 0 weeks and 12 months, preferably included between 0 weeks and 9 months, preferably included between 0 weeks and 6 months, preferably included between 0 weeks and 20 weeks, preferably included between 0 weeks and 16 weeks, preferably included between 0 weeks and 12 weeks, preferably included between 0 weeks and 8 weeks, preferably included between 2 weeks and 8 weeks, preferably included between 4 weeks and 8 weeks.

[0100] Note that preferably, PPD is characterized by symptoms selected from the group consisting of rapid mood swings, irritability, anxiety or panic attacks, decreased concentration, crying crises (collectively referred to as the "baby blues"); appetite disorders (e.g., loss of appetite or excessive eating); sleep disorders (e.g., insomnia or hypersomnia); insomnia even when the child is sleeping; psychomotor agitation or retardation; fatigue / tiredness; suicidal thoughts; depressed mood; decreased libido; headaches and myalgias; excessive concern or disinterest in the infant; feelings of uselessness or inadequacy as a mother; feelings of guilt; fear of harming the infant; and combinations thereof.

[0101] Example

[0102] 1. A capsule comprising the composition of the present invention.

[0103] For illustrative and non-limiting purposes, embodiments of the composition objects of the present invention are shown below.

[0104]

[0105]

[0106] 2. Clinical data: Evaluation of the efficacy of preparations based on natural substances such as Ashwagandha (150 mg), Lavender OE (100 mg), Lemon Balm (100 mg) and added vitamin D3 (50 μg) in the treatment of postpartum depression.

[0107] The study aims to evaluate the efficacy and tolerability of a new product consisting of natural substances capable of resisting and preventing the onset of postpartum depression.

[0108] 50 women aged 18 to 40 were recruited in the first week after natural childbirth or caesarean section, and they were diagnosed with postpartum depression by self-assessment by completing the EPDS questionnaire (Edinburgh Postnatal Depression Scale). EPDS is a self-assessment questionnaire consisting of 10 items investigating the presence and intensity of depressive symptoms, including: anhedonia, guilt, anxiety, fear or panic, sadness and crying, sense of failure, difficulty sleeping, thoughts of hurting oneself. Women can choose between four answers, and their scores (0-3) vary in an increasing manner according to the severity of the symptoms investigated. The lowest and highest scores are 0 and 30.

[0109] When the score was >12.5, the woman defined herself as having PPD.

[0110] The women enrolled in the study were treated with a monotherapy comprising daily administration of a solid oral composition (capsule) according to Example 1 for 12 weeks.

[0111] After 6 weeks (T1) and 12 weeks (T2) from the start of treatment (T0) with this new phytotherapeutic (nutraceutical) product, the patients filled in the questionnaire again.

[0112] 2.1 EPDS Questionnaire

[0113] The following are the contents of the EPDS form for the purposes of the clinical study in question:

[0114]

[0115]

[0116] EPDS questionnaire (10 items scored from 0 to 3 in descending order indicating well-being); women scoring between 0 and 12 were not depressed, and those scoring between 13 and 30 were probably or definitely diagnosed with postpartum depression.

[0117] 2.2 Results

[0118] Figure 2A-2L For each item of the questionnaire, the arithmetic mean of the scores given by each patient from the beginning of the treatment to the end of the study (T0, T1, T2) is shown.

[0119] Figure 1 The mean of the sum of the scores recorded for each item of the EPDS questionnaire for each patient from the start of treatment to the end of the study (T0, T1, T2) is shown.

[0120] In the following Table 1, it is shown that Figure 1(sum of scores) and Figure 2A-2L The same values ​​found in (arithmetic mean of each patient's score) and the relative standard deviation (SD) readings.

[0121]

[0122] Table 1: Scores and associated standard deviations obtained by processing the data collected at the end of the clinical study: These values ​​represent both the mean score obtained for each item of the questionnaire (items 1-10) and the sum (Sum) of the mean scores recorded for each item of the questionnaire.

[0123] For the purpose of comparing the mean values ​​of the scores at T0-T1 and T1-T2, a t-test (paired, two-tailed t-test) was applied; to evaluate the significance of the differences in scores found at T1 relative to T0 and at T2 relative to T1, p-values ​​were also calculated, with a threshold α of 0.001.

[0124] from Figure 2A-2L It can be seen that for each item of the EPDS questionnaire, the scores decreased over time.

[0125] The sum of the average scores was statistically analyzed ( Figure 1 ) to assess whether the treatment resulted in a significant overall improvement in the sum of the mean scores and, therefore, in a significant overall improvement in the patients examined; the scores of the individual items (i.e., each question) that make up the EPDS questionnaire were also statistically analyzed to assess whether the treatment resulted in a significant improvement in the presence and intensity of the target depressive symptoms (anhedonia, feelings of guilt, anxiety, fear or panic, sadness and crying, feelings of failure, difficulty sleeping, thoughts of harming oneself).

[0126] Considering that the minimum score for diagnosing PPD through EPDS is 12.5, Figure 1 It can be noted that the sum of the mean scores decreases significantly, from a value of 20.56 to a value of 12.98, already 6 weeks after the start of treatment (T0-T1: p<0.001), thus approaching the threshold that allows to distinguish the presence or absence of pathology. After 12 weeks from the start of treatment, the score decreases significantly below this threshold. Note that the decrease recorded between time T2 and time T1 is also significant (T2-T1: p<0.001). Overall ( Figure 1 ), the sum of the average scores recorded at time T2 is reduced by approximately 61% compared to the average scores recorded at time T0, and is reduced by approximately 38% compared to the average scores recorded at time T1.

[0127] For each test item (i.e., for each question), the score reduction recorded 6 weeks after the start of treatment (T0-T1) and the score reduction recorded 6 weeks after half of the treatment (T1-T2) were significant (p<0.001). It can therefore be concluded that the composition object of the present invention is effective in the treatment of postpartum depression.

Claims

1. A composition comprising as active ingredients: - dry extract of Withania somnifera, - dry extract of lemon balm, and - Microencapsulated essential oil of Lavandula angustifolia, The composition is used for preventing and / or treating postpartum depression (PPD).

2. A composition for use according to claim 1 as an adjuvant in drug therapy.

3. A composition for use according to claim 1 or 2 for the prevention of PPD in the following populations: - pregnant women, preferably between the 35th and 40th week of pregnancy, or - Postpartum women in the neonatal period included between 0 and 6 weeks after delivery.

4. A composition for use according to any one of claims 1 to 3 for the treatment of PPD in postpartum women.

5. A composition for use according to claim 4 for the treatment of PPD in a postpartum woman during the neonatal period comprised between 0 weeks and 24 months.

6. A composition for use according to any one of claims 1 to 5, wherein PPD is characterized by symptoms selected from the group consisting of: rapid mood swings, irritability, anxiety or panic attacks, decreased concentration, crying crises; appetite disturbances; sleep disturbances or insomnia even when the child is sleeping; psychomotor agitation or retardation; fatigue / tiredness; suicidal thoughts; depressed mood; decreased libido; headaches and myalgias; excessive concern or disinterest in the infant; feelings of worthlessness or inadequacy as a mother; feelings of guilt; fear of harming the infant; and combinations thereof.

7. A composition for use according to any one of claims 1 to 6, comprising per dosing unit: - a dry extract of Withania somnifera in a concentration comprised between 30% and 40% (w / w), - a dry extract of Melissa officinalis in a concentration comprised between 20% and 30% (w / w), - microencapsulated essential oil of Lavandula angustifolia in a concentration comprised between 20% and 30% (w / w).

8. Composition for use according to any one of claims 1 to 7, comprising as a further active ingredient vitamin D3, preferably in a concentration comprised between 3% and 8% (w / w), per administration unit.

9. A composition for use according to any one of claims 1 to 8, characterised in that The daily dose is 1 or 2 dosing units.

10. A composition for use according to any one of claims 1 to 9 in solid form, preferably in the form of a tablet, capsule or powder.

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