Herbal composition for use in the treatment or prevention of postpartum depression

Abstract

The present invention relates to a composition for use in the prevention and / or treatment of postpartum depression (PPD) comprising, as active ingredients, a dry extract of Withania somnifera, a dry extract of Melissa officinalis, an essential oil of microencapsulated lavender, and optionally vitamin D.

Description

Technical Field

[0001] The composition of the present invention belongs to the technical field of a composition or combination of active ingredients useful for the treatment of postpartum depression.

Background Art

[0002] After childbirth, approximately 8 - 12% of new mothers suffer from a major depressive disorder known as postpartum depression. Postpartum depression (PPD), which constitutes one of the most common medical complications during the postpartum period, includes major depressive episodes and minor depressive episodes that occur during pregnancy or within 12 months after childbirth, and affects 1 in 7 women. PPD can have a devastating impact on women, children, and families. Maternal suicide is the leading cause of death among pregnant and postpartum women, exceeding hemorrhagic diseases and hypertensive disorders.

[0003] Compared to depression that occurs at times other than postpartum, PPD has been scarcely studied so far, but discussions have started in the latest scientific literature about the definition of this disorder, and more specifically, about the differences between PPD and depression that occurs at times other than postpartum.

[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) have clarified the reasons why postpartum depression (PPD) should be considered as a distinct pathology from depression. In particular, the reasons supporting the differences between the two pathologies are: 1) Guidelines: There are guidelines specialized for postpartum depression (e.g., NICE and SIGN guidelines). This is because the identification and treatment of women with PPD require special considerations that are not usually applicable to depression outside the perinatal period. In addition, the treatment needs of women with PPD are different from those of women with ordinary depression and often require a multidisciplinary approach (physicians need to consider the effects of antidepressants during lactation and recognize and treat the mother in the context of her relationship with the child). 2) Prognosis and outcome: Some epidemiological and clinical studies suggest a relationship between bipolar disposition and PPD; since there is evidence of a relationship between childbirth and bipolar disorder, physicians need to pay particular attention to the evaluation, treatment, and follow-up of women with PPD. This is because they are at high risk of bipolar disposition. This feature also differentiates 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 outside the perinatal period. Therefore, it seems reasonable that these two pathologies require different treatments and clinical interventions, which strengthens the idea of considering these two pathologies as separate pathologies. 4) Epidemiology : According to many epidemiological and clinical studies, depression is shown to be more common postpartum than at other times in a woman's life, suggesting an exact etiological relationship with this specific period in a woman's life.

[0005] Batt (Melissa M Batt, "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) addresses the similarities and differences between PPD and depression outside the perinatal period. In particular, considering the period up to 8 weeks after childbirth as the postpartum period, it is pointed out that the distinction between the two types of depression is very clear. This is because within this time frame, the symptom severity, hormone levels, genetics, epigenetic data, and response to treatment are different from those in the postpartum period after 8 weeks. After 8 weeks, it becomes more similar to that of depression occurring outside the perinatal period.

[0006] Regarding treatment, it is also considered that there may be benefits in the treatment of early PPD compared to late PPD. Late PPD responds to treatment rather as if it were a normal depression. 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 is different from other depressions due to the particularity of this period in a woman's life and the possibility that this type of depression can affect not only the woman but also the child. This publication also emphasizes the fact that there are no approved antidepressants for postpartum depression in Europe. Therefore, it is the responsibility of the attending physician to prescribe antidepressants during this very delicate period of a woman's life. Antidepressants cannot actually be used during breastfeeding and may also change a woman's ability to care for the baby (for example, sedatives).

[0007] Comparative studies were also conducted with the aim of comparing the symptoms and biological responses of normal depressive patients with those of PPD patients or patients in a state like PPD. In a retrospective study, the symptoms and responses to treatment of 26 women with PPD and 25 women with normal depression were compared, and the following points were noted.

[0008] - Women with PPD experienced a more intense state of anxiety and more severe depression than women with normal depression; - In women with PPD, the response time to drug therapy was longer than that of women with normal depression (6 weeks vs. 3 weeks); - When the response to drug therapy was achieved, 60% of women with PPD were treated with multiple antidepressants rather than a single antidepressant (compared with 4% of women with normal depression).

[0009] Therefore, the authors concluded that there were clear differences between PPD and normal depression. Women with PPD actually had more pronounced anxiety characteristics, took longer to respond to antidepressants, and required the use of more antidepressants 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).

[0010] O’Brien (O’Brien S et al., "Is postnatal depression a distinct subtype of major depressive disorder? An exploratory study". Arch Womens Ment Health. 2021 Apr;24(2):329-333) conducted an exploratory study to examine whether women with a history of PPD have specific differences in brain activation compared to women with normal depression. This examination was carried out by subjecting the registered women to a functional magnetic resonance imaging (fMRI) scan that measures brain activation at the level of the amygdala, a nuclear group located in the temporal lobe of the brain that manages emotions.

[0011] This study was based on the results of two previous studies. In the first study (Groenewold et al., 2013), it was observed that women with a history of depression (not PPD) who underwent fMRI experienced an increase in amygdala activation when exposed to negative facial expressions. In the second study (Moses-Kolko et al., 2010), conversely, it was observed that women with PPD experienced a decrease in amygdala activation when exposed to negative facial expressions.

[0012] The aim of O’Brien et al.’s study was a direct comparison between women with a history of normal depression and women with a history of PPD (vs control). It has also been shown that the main factor contributing to the onset of PPD is the rapid decline of sex hormones that occurs after childbirth. Women with a tendency to PPD are actually particularly sensitive to these changes. This is why the measurements in O’Brien et al.’s exploratory study were made in the late luteal phase of the menstrual cycle. Because the rapid decline in estradiol and plasma progesterone concentrations during this period is similar to the postpartum hormonal environment, albeit in a modified form. In this way, it became possible to evaluate the way in which the brain activation changes in women with PPD and women with normal depression under circumstances that simulate the postpartum hormonal state.

[0013] From the study by O'Brien et al., it was revealed that women with a history of PPD had reduced brain activity in the tonsils compared to women with a history of ordinary depression. Therefore, a hypothesis was put forward that in women who develop PPD, brain activation is different compared to women who develop ordinary depression. This supports the idea that the two pathologies are different from each other.

[0014] Problems of the background art The existence of PPD is known to many people, but there is little knowledge about the pharmacological management of patients, and patients may sometimes be treated with the same therapies used to treat major depressive disorders that occur at times other than the postpartum period.

[0015] This measure is inappropriate. This is because therapies that can have an adverse impact on the child need to be avoided. The adverse impact is either directly due to exposure to drug therapy through breastfeeding or indirectly due to the possibility that the mother's mood and temperament may change due to the current drug therapy.

[0016] As emphasized by the NICE guidelines, currently in Europe, there are no approved psychotropic drugs for postpartum depression, and attending physicians are in a position where they have to evaluate on a case-by-case basis which therapy to prescribe in order to treat the mother while minimizing the possible impact on the child.

[0017] Due to this difference in clinical practice and also because of the different symptom profiles compared to ordinary depression, PPD should be regarded as a distinct pathology. Compared to mothers without depression, mothers with PPD tend to have a lower quality of interaction with their children, such as greater disconnection or less positive affection. These aspects of PPD affect both the mother's behavior, her satisfaction with her role, and also the child in ensuring optimal developmental outcomes. PPD is actually associated with deficits in the child's cognitive and socioemotional development, and there is also evidence suggesting that the quality of the mother-child relationship mediates such developmental outcomes (Melissa M Batt et al., "Is postpartum depression different from depression that onsets outside the perinatal period? A review of the evidence." Focus (Am Psychiatr Publ) 2020 Apr;18(2):106-119).

[0018] Therefore, there is a need to prepare natural products that can be used without problems during the postpartum period and while breastfeeding. Advanced technologies include natural therapies useful for the treatment of disorders resulting from anxiety disorders or depressive forms. However, none of these have been applied to the prevention and / or treatment of postpartum depression in the advanced technologies.

[0019] EP1796702 describes the use of lavender oil (Lavandula angustifolia;

[0009] ) in the treatment of patients suffering from somatic disorders and post-traumatic stress disorder (PTSD; paragraph

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

[0017] ).

[0020] WO2011 / 098394 describes compositions for the treatment and prevention of neurological disorders and sleep disorders. The compositions contain extracts / tinctures of the following plants: Lavandula angustifolia, Humulus lupulus, Melissa officinalis, Passiflora incarnata, and Valeriana officinalis (page 1, paragraphs 12 - 13). Neurological disorders are defined in the literature as characterized by hyper-excitability, irritability (excitability, irascibility), sleep disorders, insomnia, resignation, depressive detuning, decreased libido, exhaustion, anxiety, nervousness, menopausal disorders, shortness of breath, headache, migraine, muscle contraction or cramps, heart problems (arrhythmia, angina), and convulsions of the stomach, intestines, or bladder, etc. (page 2, paragraph 3).

[0021] WO2007 / 014334 describes pharmaceuticals, veterinary pharmaceuticals, or dietary supplements containing an extract of Withania somnifera at a concentration of 0.05% to 99% by weight. This composition may also contain other active ingredients such as antioxidants, vitamins, minerals, or plant extracts (page 6, lines 1 - 3). This composition is intended for the treatment of stress disorders characterized by symptoms including insomnia, palpitations, sweating, fatigue, irritability, and a sense of inescapable / imminent fate (claim 10).

[0022] WO2020 / 144591 describes a delivery system for Withania somnifera, in particular, a core containing solid particles (preferably consisting of saccharides or derivatives; page 6, lines 9 - 11) and a layer of Withania somnifera extract covering the particles; and a layer (page 2, lines 19 - 25) disposed on the core and having a function of protecting Withania somnifera from the attack by gastric juice, including a solid dosage form. This composition has several biological activities such as immunomodulation, reduction of depressive state or anxiety, improvement of sleep disorder, improvement of male testosterone level, and prolongation of sexual behavior. This composition aimed at treating depression, anxiety, and sleep disorder is administered to a subject having these disorders at a dosage containing 10 mg to 2000 mg (page 6, line 27 - page 7, line 6).

Prior Art Documents

Patent Documents

[0023]

Patent Document 1

Patent Document 2

Patent Document 3

Patent Document 4

Non - Patent Documents

[0024]

Non - Patent Document 1

Non - Patent Document 2

Non - Patent Document 3

Non - Patent Document 4

Summary of the Invention

[0025] The applicant has recently identified a composition useful for the prevention and treatment of postpartum depression that solves the problems of the prior art. This composition contains, as active ingredients (effective ingredients), - Dried extract of Withania somnifera, - Dried extract of Melissa officinalis, and - Microencapsulated essential oil of Lavandula angustifolia and includes.

[0026] According to a particularly preferred embodiment, the composition may further contain vitamin D3. Advantages of the present invention The composition developed by the applicant is beneficial for the following reasons.

[0027] - Since it is a natural product, it is safe for use by women during pregnancy or lactation. - As a treatment for postpartum depression, it provides patients and physicians with a specific treatment proposal for PPD that currently does not exist.

[0028] - Since it can be taken alone or as an adjuvant to drug therapy with conventional antidepressants or anxiolytics, it is possible to reduce the number of conventional drug treatments. As shown in the literature, in fact, 60% of women with PPD are treated with more antidepressants compared to 4% of women with normal depression (Hendrick V et al., "Postpartum Depression and Depression Outside of Postpartum: Differences in Symptoms and Response to Pharmacotherapy". Depress Anxiety 2000;11(2):66 - 72).

Brief Description of the Drawings

[0029]

Figure 1

Figure 2A

Figure 2B

Figure 2C

Figure 2D

Figure 2E

Figure 2F

Figure 2G

Figure 2H

Figure 2I

Figure 2L

Modes for Carrying Out the Invention

[0030] Composition As can be predicted from the summary of the invention, the composition to be protected contains, as active ingredients - a dry extract of Withania somnifera, - a dry extract of Melissa officinalis, and - an essential oil of microencapsulated Lavandula angustifolia in it.

[0031] Since the dry extract of Withania somnifera, the dry extract of Melissa officinalis, and the essential oil of microencapsulated Lavandula angustifolia are active ingredients of plant origin, they are also referred to as "herbs" or "herbal active ingredients" in the present text.

[0032] According to a preferred embodiment, the dry extract of Withania somnifera, the dry extract of Melissa officinalis, and the essential oil of microencapsulated Lavandula angustifolia constitute the only herbal active ingredients of the composition which is the subject of the present invention.

[0033] Although the applicant does not have corroborating experimental evidence at present, it is considered that the combination of the dry extract of Withania somnifera, the dry extract of Melissa officinalis, and the essential oil of microencapsulated Lavandula angustifolia may have a synergistic effect in the prevention and treatment of postpartum depression and the prevention and treatment of the accompanying symptoms.

[0034] Preferably, the composition does not contain the following: Hawthorn such as Crataegus pinnatifida or Crataegus Oxyacantha, or their extracts / derivatives; True Lavender (Lavandula officinalis) or its extracts / derivatives; Hops (Humuls lupulus) or its extracts / derivatives; Extracts / derivatives of Valeriana officinalis; Cinnamomum cassia or its extracts / derivatives; Fruits of the genus Citrus such as Citrus bergamia, Citrus Union, Citrus paradisi, or their extracts / derivatives.

[0035] Withania somnifera has been used in medicine since Ayurveda, an ancient Indian medical system. Withania somnifera has been used as an aphrodisiac, liver tonic, anti-inflammatory, astringent, and to treat bronchitis, asthma, ulcers, debility, insomnia, and senile dementia. More recently, Withania somnifera has been proven useful in the treatment of anxiety, cognition and neuropathy, inflammation, and Parkinson's disease (Singh, G & Sharma, P.K. & Dudhe, Rupesh & Singh, Sukhdev. (2009). Biological activities of Withania somnifera. Ann Biol Res. 1).

[0036] For the purposes of the present invention, the dried extract of Withania somnifera (W. somnifera) is preferably an extract of the roots of the plant. Furthermore, the extract of Withania somnifera is preferably characterized by having a thiol content of ≥ 5% by weight in total withanolides, based on the total weight of the extract; and a withaferin A titer of < 0.1% by weight, based on the total weight of the extract.

[0037] Lemon balm (M. officinalis) has been long used in several ethnomedical (folk medicine) approaches, especially traditional medicine, for the treatment of several diseases (health syndromes of the nervous, central nervous, cardiovascular systems, etc.); as an antibacterial, antidepressant, and memory enhancer for dementia patients (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 )。

[0038] For the purposes of the present invention, the dried extract of lemon balm (M. officinalis) is preferably an extract of the leaves of the plant and preferably has an extract / drug ratio of 1:4 to 1:6. Further, the dried extract of lemon balm preferably has a thiol in rosmarinic acid of ≥12% by weight, based on the total weight of the extract.

[0039] Lavender essential oil is used in various cosmetics and therapeutic products. Oils obtained from various lavenders have been shown to have numerous biological activities. Lavender is well-known and valued as a fragrant herb in the cosmetics, food, and pharmaceutical industries. Lavender essential oil is widely sold as a commercial phytotherapy for treating depression, anxiety, and stress. International agencies, including the World Health Organization (WHO), the European Medicines Agency (EMA), and the European Scientific Cooperative on Phytotherapy (ESCOP), recognize lavender as an approved therapeutic agent for alleviating anxiety, stress, and restlessness.

[0040] For the purposes of the present invention, the lavender essential oil is preferably an extract of the flowers of lavender (L. angustifolia). The essential oil is in microencapsulated form. Microencapsulation means a delivery technology in which the active ingredient is incorporated into a particle structure with a coating suitable for maintaining the biological, functional and physicochemical properties of the core material. Microencapsulation of essential oils is known to those skilled in the art and can generally be achieved by various methods, such as emulsification, spray drying, coaxial electrospray, freeze drying, coacervation, in-situ polymerization, melt extrusion, supercritical fluid utilization technology, and fluidized bed coating. Coacervation and spray drying are the most commonly used techniques for microencapsulation of essential oils.

[0041] According to a preferred embodiment, the microcapsules of lavender essential oil contain about 80% to 90% by weight of essential oil, preferably about 85% to 90% of essential oil. Preferably, the microcapsules of lavender essential oil are characterized by a particle size of about 100 μm to 600 μm (more precisely, 80% of the particle population of the microencapsulated lavender essential oil sample has a particle size of 100 μm to 600 μm as measured by dynamic light scattering).

[0042] More preferably, the lavender essential oil contained in the microcapsules has a potency of about 30% to about 40% by weight of linalool based on the total weight of the essential oil; about 30% to about 40% by weight of linalyl acetate based on the total weight of the essential oil; and about 30% to about 40% by weight of linaryl acetate based on the total weight of the essential oil.

[0043] Preferably, the dried extract of ashwagandha is contained in the composition at a concentration of about 30% to 40% by weight, preferably about 32% to 38% by weight, preferably about 35% to 38% by weight, based on the total weight of the composition.

[0044] Preferably, the dried extract of lemon balm is contained in the composition at a concentration of about 20% to 30% by weight, preferably about 22% to 27% by weight, preferably about 23% to 26% by weight, based on the total weight of the composition.

[0045] Preferably, the microencapsulated lavender essential oil is contained in the composition at a concentration of about 20% to 30% by weight, preferably about 22% to 27%, about 23% to 26% based on the total weight of the composition.

[0046] According to a preferred embodiment, the dosage unit of the composition is - a dried extract of Withania somnifera at a concentration of 30% to 40% (w / w) (preferably having a withanolide titer of ≧5%); - a dried extract of Melissa officinalis at a concentration of 20% to 30% (w / w) (preferably having a rosmarinic acid titer of ≧12%); and - a microencapsulated essential oil of Lavandula angustifolia at a concentration of 20% to 30% (w / w) (the essential oil is preferably characterized by a linalool titer of 30% to 40%) and contains.

[0047] According to a particularly preferred embodiment, the composition contains vitamin D3 as a further (non-herbal) active ingredient. Preferably, the dosage unit of the composition contains vitamin D3 at a concentration of 3% to 8% by weight based on the total weight of the composition.

[0048] Note that preferably, vitamin D3 is the only vitamin present in the composition of the present invention. The benefits resulting from the combination of vitamin D3 and the aforementioned active ingredient are derived from the fact that a direct correlation between vitamin D deficiency and the onset or progression of postpartum depression has been shown in the scientific literature (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., “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;17:213 9; Fu CW et al., “Association between serum 25 hydroxyvitamin D levels measured 24 hours after delivery and postpartum depression”, BJOG 2015;122:1688 94).

[0049] 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. Twenty-seven women participated in this study (randomized double blind) and were divided into three groups (ratio 1:1:1).

[0050] - Group 1: Vitamin D + 500 mg of calcium - Group 2: Vitamin D + calcium placebo - Group 3: Vitamin D placebo + calcium placebo (control) The treatment continued for 8 weeks, and at the end, vitamin D levels and EPDS scores were compared to the baseline. The scores on the EPDS questionnaire decreased significantly from baseline in the groups treated with (vitamin D + calcium) and (vitamin D + calcium placebo) compared to the control group treated with placebo only. Furthermore, the effect of vitamin D on the EPDS score was greater in the group treated with vitamin D only without adding calcium. Therefore, the authors concluded that vitamin D might be effective in improving the clinical symptoms of PPD.

[0051] According to a preferred embodiment, the dosage unit of the composition is - a dried extract of Withania somnifera at a concentration of 30% to 40% (w / w) (preferably having a withanolide titer of ≧ 5%); - Dried extract of Melissa officinalis at a concentration of 20% to 30% (w / w) (preferably having a rosmarinic acid titer of ≧12%); and - Microencapsulated essential oil of Lavandula angustifolia at a concentration of 20% to 30% (w / w) (the essential oil is preferably characterized by a linalool titer of 30% to 40%) - Vitamin D3 at a concentration of 3% to 8% (w / w) Containing.

[0052] Preferably, the composition of the present invention also contains suitable excipients and / or diluents useful for formulating products intended for oral ingestion. By way of example, the excipients and / or diluents can be selected from anticoagulants (such as microcrystalline cellulose), bulking agents, anti-packing agents or fluidizing agents (such as silicon dioxide), emulsifiers, glidating agents (such as magnesium salts of fatty acids), stabilizers, pigments, flavoring agents.

[0053] According to a preferred embodiment of the present invention, the dried extract of Withania somnifera, the dried extract of Melissa officinalis, the microencapsulated essential oil of Lavandula angustifolia, and vitamin D3 constitute the only active ingredients of the composition which is the subject of the present invention.

[0054] Dosage form of the composition Preferably, the composition of the present invention is intended for oral administration. Preferably, the composition of the present invention is characterized in that the daily dose is 1 or 2 dosage units.

[0055] Preferably, the composition, i.e., the dosage unit of the composition, is in solid or liquid form, preferably solid. More preferably, the composition, i.e., the dosage unit of the composition, is in the form of solid tablets, capsules, or powders / granules.

[0056] Preferably, when the composition is in the form of a powder / granule, the powder / granule is dissolved in water before administration or is orally absorbed. According to a preferred embodiment, the composition of the present invention is a nutritional supplement.

[0057] A nutritional supplement means a preparation that falls within the scope of the basic definition of Directive 2002 / 46 / EC of the Council, as amended. In this Directive, nutritional supplements are precisely defined as follows: "Foods intended to supplement the normal diet, which are concentrates of nutrients such as vitamins and minerals or other substances having a nutritional or nutritional or physiological effect, in particular amino acids, essential fatty acids, dietary fiber and extracts of plant origin, which are single compounds and multi-component compounds in a pre-dosed form, but are not limited thereto." Medical use As emphasized in the Summary of the Invention section, the disclosed composition is intended for the prevention and treatment of postpartum depression (PPD).

[0058] According to a preferred embodiment, the present composition is used as an adjuvant to drug therapy. The treatment of PPD varies depending on the patient and generally includes psychological intervention (psychotherapy), and / or the use of neuroactive drugs (sedatives, anxiolytics, mood regulators, antidepressants) (both with appropriate caution), and / or the use of natural therapeutic substances (e.g., Hypericum perforatum, which is representative of substances used for PPD, but which is not without side effects). Note that in most cases, PPD develops in postpartum women during the puerperium of 4 to 6 weeks after childbirth (Melissa M Batt et al., "Is postpartum depression different from depression occurring outside 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).

[0059] Note that in most cases, PPD develops in postpartum women during the puerperium of 4 to 6 weeks after childbirth (Melissa M Batt et al., "Is postpartum depression different from depression occurring outside 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).

[0060] Preferably, the present composition is - for pregnant women, preferably pregnant women at 35 to 40 weeks of pregnancy; or - for puerperae in the neonatal period from 0 to 6 weeks after childbirth, preferably from 2 to 6 weeks, preferably from 2 to 4 weeks Note that it is suitable for the prevention of PPD.

[0061] According to a preferred embodiment, the present composition is taken by pregnant women in the last few weeks of pregnancy, and the therapy can continue during the postpartum period (also called the neonatal period). Preferably, the present composition is useful for the treatment of PPD in puerperae. Furthermore, the present composition is useful for the treatment of puerperae in the neonatal period from 0 weeks to 24 months, preferably from 0 weeks to 18 months, preferably from 0 weeks to 12 months, preferably from 0 weeks to 9 months, preferably from 0 weeks to 6 months, preferably from 0 weeks to 20 weeks, preferably from 0 weeks to 16 weeks, preferably from 0 weeks to 12 weeks, preferably from 0 weeks to 8 weeks, preferably from 2 weeks to 8 weeks, preferably from 4 weeks to 8 weeks.

[0062] Preferably, note that PPD is characterized by symptoms selected from the group consisting of severe mood changes, irritability, anxiety or panic attacks, decreased concentration, crying crises (collectively known as "baby blues"); eating disorders (such as anorexia or bulimia); sleep disorders (such as insomnia or hypersomnia); inability to sleep even during the baby's sleep; psychomotor agitation or retardation; lethargy / fatigue; suicidal thoughts; depressive mood; decreased libido; headache and muscle pain; excessive concern or indifference towards the baby; a sense of powerlessness or inferiority as a mother; guilt; fear of harming the baby, and combinations thereof.

Examples

[0063] 1. Capsules containing the composition of the present invention For illustrative and non-limiting purposes, one embodiment of the composition which is the subject of the present invention is shown below.

[0064]

Table A

[0065] 2. Clinical data: Evaluation of the efficacy of a formulation containing vitamin D3 (50 μg) based on natural substances such as ashwagandha (150 mg), lavender O.E. (100 mg), and lemon balm (100 g) in the treatment of postpartum depression The purpose of this study is to evaluate the efficacy and tolerance of a new product composed of natural substances that can suppress and prevent the onset of postpartum depression

[0066] Fifty women aged 18 to 40 years diagnosed with postpartum depression by self - evaluation through filling out the EPDS questionnaire (Edinburgh Postnatal Depression Scale) in the first week after natural childbirth or cesarean section were recruited. The EPDS is a self - evaluation questionnaire consisting of 10 items that examines the presence and intensity of depressive symptoms related to anhedonia, guilt, anxiety, fear or panic, sadness and crying, frustration, sleep difficulties, and self - harm thoughts. Women can choose from four responses, and the score (0 - 3) increases according to the severity of the symptoms investigated. The minimum and maximum scores are 0 and 30

[0067] Women are considered to have PPD if their score is > 12.5 The women participating in this study were treated with monotherapy including daily administration of the solid oral composition (capsule) according to Example 1 for 12 weeks

[0068] Patients filled out the questionnaire again 6 weeks (T1) and 12 weeks (T2) after the start of treatment (T0) with this new phytotherapy (nutritional supplement) product 2.1 EPDS questionnaire The following is the content of the English version of the EPDS form used for the purpose of the clinical study in question

[0069]

Table B - 1

[0070]

Table B - 2

[0071] 2.2 Results Figures 2A - 2L show the arithmetic mean of the scores obtained from each patient from the start of treatment to the end of the study (T0, T1, T2) for each item of the questionnaire.

[0072] Figure 1 shows the mean of the total scores recorded by each patient from the start of treatment to the end of the study (T0, T1, T2) for each item of the EPDS questionnaire. The following Table 1 shows the same values as seen in Figure 1 (total scores) and Figures 2A - 2L (arithmetic mean of scores for each patient), along with the notation of the relative standard deviation (SD).

[0073] [Table 1]

[0074] To compare the mean scores at two time points T0 - T1 and T1 - T2, a t - test (paired two - sided t - test) was applied. To evaluate the significance of the difference in scores seen at T1 compared to T0 and the significance of the difference in scores seen at T2 compared to T1, the p - value was also calculated with a threshold α of 0.001.

[0075] As can be seen from Figures 2A - 2L, for each item of the EPDS questionnaire, a decrease in scores is seen over time. Statistical analysis was performed on the total mean score (Figure 1) to evaluate whether the treatment brought about a significant overall improvement in the total mean score, i.e., in the patients under study; it was also performed on the scores of the individual items (i.e., each question) that make up the EPDS questionnaire to evaluate whether the treatment brought about a significant improvement with respect to the presence and intensity of the problem depressive symptoms (anhedonia, guilt, anxiety, fear or panic, sadness and crying, frustration, sleep difficulties, self - harm thoughts).

[0076] Considering that the minimum score for PPD diagnosis by EPDS is 12.5, it can be seen from Figure 1 that the total average score has significantly decreased from 20.56 to 12.98 already at 6 weeks after the start of treatment (T0 - T1: p < 0.001), approaching the threshold that enables differentiation between the presence and absence of the disease. This score significantly drops below this threshold 12 weeks after the start of treatment. Note that the decrease recorded between T2 and T1 is also significant (T1 - T2: p < 0.001). Generally (Figure 1), the total average score recorded at T2 decreased by approximately 61% compared to the average score recorded at T0, and by approximately 38% compared to the average score recorded at T1.

[0077] For each test item (i.e., each question), the decrease in the score recorded at 6 weeks after the start of treatment (T0 - T1) and the decrease in the score recorded at 6 weeks after half of the treatment (T1 - T2) were also significant (p < 0.001). Therefore, it can be concluded that the composition of the present invention was effective in the treatment of postpartum depression.

Claims

1. A composition for use in the prevention and / or treatment of postpartum depression (PPD), comprising: - a dry extract of Withania somnifera (L.); - a dry extract of Melissa officinalis (L.), and - an essential oil of microencapsulated Lavandula angustifolia as active ingredients.

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

3. - a pregnant woman, preferably a pregnant woman at 35 to 40 weeks of gestation; or - a puerpera in the neonatal period from 0 to 6 weeks postpartum A composition for use as claimed in claim 1 or 2 in the prevention of PPD.

4. A composition for use as claimed in any one of claims 1 to 3 in the treatment of PPD in puerperas.

5. A composition for use as claimed in claim 4 in the treatment of PPD in puerperas in the neonatal period from 0 to 24 months.

6. PPD is characterized by symptoms selected from the group consisting of severe mood swings, irritability, anxiety or panic attacks, decreased concentration, crying crises; eating disorders; sleep disorders or inability to sleep even during the baby's sleep; psychomotor agitation or retardation; lethargy / fatigue; suicidal thoughts; depressive mood; decreased libido; headache and muscle pain; excessive worry or indifference towards the baby; a sense of powerlessness or inferiority as a mother; guilt; fear of harming the baby, and combinations thereof. A composition for use as claimed in any one of claims 1 to 5.

7. Per dosage unit, - a dry extract of Withania somnifera at a concentration of 30% to 40% (w / w), - a dry extract of Melissa officinalis at a concentration of 20% to 30% (w / w), - an essential oil of microencapsulated Lavandula angustifolia at a concentration of 20% to 30% (w / w) A composition for use as claimed in any one of claims 1 to 6.

8. As a further active ingredient, per dosage unit, preferably containing vitamin D3 at a concentration of 3% to 8% (w / w). A composition for use as claimed in any one of claims 1 to 7.

9. A composition for use as claimed in any one of claims 1 to 8, characterized in that the daily dose is 1 or 2 dosage units.

10. The composition according to any one of claims 1 to 9, which is in solid form, preferably in the form of tablets, capsules or powders.

Images