Compositions and methods useful for management of stress and anxiety

Abstract

Provided herein a composition comprising traditional Chinese remedies, as a formula useful to treating or prophylaxis of anxiety and / or stress-related conditions in a patient in need thereof.

Description

COMPOSITIONS AND METHODS USEFUL FOR MANAGEMENT OF STRESS ANDANXIETYFIELD OF THE INVENTION

[0001] The invention relates to the field of health care and more specifically, to compositions and methods, the compositions and methods useful for treating conditions caused or characterized by elevated stress and / or anxiety. Particularly, compositions comprising combinations of traditional Chinese remedies are disclosed.BACKGROUND

[0002] Anxiety is an unpleasant future-oriented mood state involving unease, worry, fear, general nervousness, and can manifest itself under many circumstances. Everyone has experienced or will experience anxiety more than once during their lifetime. Anxiety may be provoked by a variety of causes, both external, such as stress, overload, danger or a threat thereof, as well as by internal factors. Anxiety is a normal reaction to stress. Mild anxiety may increase the alertness in stressful situations. Abnormal anxiety is a complex cognitive, affective, physiological, and behavioral response system which involves panic, excessive fear, which is out of proportion to the situation and age, and may significantly hinder the ability of the affected person to function normally. Many types of anxiety disorders have been recognized by the Western medicine, including generalized anxiety disorder, panic, phobias, and many others. Related conditions include post-traumatic stress disorder, obsessive-compulsive disorder, and several other psychiatric conditions. Physiologically, anxiety involves amygdala and limbic system structures in the prefrontal cortex regions of the brain, and prefrontal-limbic activation abnormalities may be reversed with psychological or pharmacologic interventions. Noradrenaline, serotonin, dopamine, and gamma-aminobutyric acid have been implicated in the emergence and modulation of anxiety pathophysiology. The autonomic nervous system, especially the sympathetic nervous system, mediates most of the symptoms. Conventionally, anxiety disorders are treated with tranquilizers, such as benzodiazepines, as well as neurotransmitter reuptake inhibitors, tricyclic antidepressants, and also beta-blockers to control the manifestations of anxiety.

[0003] Conversely, in Chinese medicine, due to the specific approach to the “body and spirit”, no single condition parallel to anxiety has been recognized. Anxiety is an importantsymptom, however, of what is perceived as other conditions and disbalances. For example, anxiety has been associated with palpitations, and also with irritability, insomnia, and in some cases with insanity, all of which conditions are considered connected to the disturbances of “spirit” (shen - the same word used to describe divine), or more precisely of “consciousness” shen zhi. Traditional cause for the disturbances of the spirit is considered the “essence” (jing} expenditure, as a result of shock, fright, and jitteriness. Among other traditional causes for shen disturbances are overload that can lead to insufficiency of nutritive qi and blood, causing deficiencies of heart and liver, thereby affecting also the ethereal soul him (K®). Traditionally, these disturbances are addressed by “heavy” substances that anchor, settle down, and calm the spirit, and by mildly tonifying substances that nourish the heart. The management of conditions associated with shen and him disturbances also involves addressing the underlying cause, such as qi, blood, or yin deficiency, qi constraint, phlegm heat, and blood stasis, and is therefore addressed by, inter alia, by clearing heat from the heart, draining heat from the liver, relieving liver constraint, transforming phlegm, invigorating blood and dispelling blood stasis, calming the liver and extinguishing wind, and opening the orifices. Recently, in parallel to the Western medicine, the anxiety disorder has been generally called jiao lit zheng( ).

[0004] Several formulas have been developed in the Chinese medicine over the centuries to treat various manifestations of the anxiety and stress. For example, anxiety associated with insomnia has been treated by the composition known as Heavenly Emperor Special Pill, tianwdng buxin dan -Anxiety associated with depression and menstruation cycles has been treated with Augmented Rambling Powder, jiawei xiaoydo sanOther compositions are presented in Table 1 below. As used herein, the botanical names are given in abbreviated or full Linneic terminology, as the case may be, and the traditional Chinese name given in parentheses represented by optionally atonal pinyin, and sometimes the traditional Chinese name is given in traditional hieroglyphic writing. The following traditional formulas include Heavenly Emperor Special Pill, tianwdng buxin dan - ( TWBXD; Augmented Rambling Powder, jiaweiJWXYS; Emotions Settling Pill, ding zhi wanDJW; Modified Emotions Settling Pill DJW1; Eight Treasures Decoction, ba zhen tang (All'll) BZT; SpleenRestoring Decoction, gui pi tang (GPT; Shen Calming and Emotions Setting Decoctionand Heart Nourishing Decoction yangxinTable 1

[0005] In the table 1, the reference is made to: bai shao - (radix) paeonia lactiflora; bai zi ren - (semen) platycladus orientalis; bai zhu - (rhyzoma) atractylodes macrocephala; bo he - (herba) mentha haplocalyx; chai hu - (radix) bupleurum falcatum; chuan xiong - (rhizoma) ligusticum officinale; dan shen - (radix) salvia miltiorrhiza; dang gui - (radix) angelica sinensis; fit ling - (sclerotum) wolfiporia extensa; fit shen - (white part of sclerota) wolfiporia extensa; jie geng - (radix) platycodon grandifloras; huang qi - (radix) astragalus membranaceus; long gu - fossil os dracoinis; longyan rou - (fruit) dimocarpus longan (euphrobia); mai men dong - (radix) ophiopogon japonicus; mu xiang - (radix) saussurea costus; ren shen - (radix) panax ginseng; sheng di huang - (radix) rehmannia glutinosa; shu di huang - (radix) rehmannia glutinosa (preparata); sheng jiang - (rhizoma) zingiber officinale, shi chang pu - (rhizoma) acorus calamus (tatarinowii); suan zao ren - (semen) ziziphus jujuba; tian men dong - (radix) asparagus cochinchinensis; xuan shen - (radix) scrophularia ningpoensis; wu wei zi - (fructus) schisandra chinensis; yuan zhi - (radix) polygala tenuifolia; zhi gan cao - (radix) glycyrrhiza uralensis (preparata); zhi yuan zhi - (radix) poly gala tenuifolia (preparata).

[0006] Further modifications to these formulas are sometimes made (e.g., as can be readily seen on the commercial website of Dr. Joel Penner https: / / www.americandragon.com / , last accessed on December 7th, 2023, and still available on January 13th, 2025). Recently, a scientific publication Jiaqi Xie et al, Jiawei Xiaoyao San in treatment of anxiety disorder and anxiety: A review, Chin Herb Medicines, 15 (2), 2023, 214-221, doi: 10.1016 / j.chmed.2022.12.007, reviewed the pre-clinical and clinical data pertaining to use of JWXYS.

[0007] There remains a need in the art to find a suitable traditional Chinese medicine composition for the management of generalized anxiety and stress.SUMMARY OF THE INVENTION

[0008] In one aspect, provided herein a composition comprising a combination of several traditional Chinese remedies, e.g., herbal and / or mineral materials. The composition may be useful for the management of stress and anxiety, and in conditions and pathologies conductive to stress and anxiety. In another aspect provided herein methods of making the compositions of the remedies, as well as method of managing, reducing the incidence, or preventing stress and anxiety with these compositions, and their use for the same purposes, as a further aspect.

[0009] The compositions may be useful for short- or long-term management of stress and anxiety and symptoms thereof. The compositions preferably comprise the following traditional Chinese remedies’ ingredients below enumerated in Table 2 (herein, the “7 formula”), optionally augmented by at least one of the following traditional Chinese remedies’ ingredients below enumerated in Table 3, which together with the 7-formula constitute between 60 and 100% by weight of the composition. Normally, the composition contains no further traditional Chinese remedies beyond the combinations as disclosed herein, but may contain minor component that do not affect its activity and efficacy, i.e., the compositions may be consisting essentially of the enumerated ingredients. The composition may further comprise inactive components, as may be needed and required for the preparation or processing of the pharmaceutical dosage form.Table 2

[0010] The composition may further comprise one or more, preferably at least three, of the components in the Table 3 below.Table 3

[0011] Preferably, the composition comprises the ten components presented in Table 4 below, which, likewise, constitute between 60 and 100% by weight of the composition.

[0012] The ingredients of the composition may be provided in a variety of forms according to the need, e.g., according to traditional Chinese compounding practice, as known in the art anddescribed partially herein, or as an extract, e.g., an aqueous extract, an organic extract, a standardized extract, a concentrated extract, e.g., x5 concentrate, or as a tincture, or as a dried extract, or as any combination of these forms for one or more of the components.Table 4

[0013] The compositions according to the invention may be used for treating of a condition characterized by stress and / or anxiety, generally classified in a subclass 06 or 07 of the 11threvision of World Health Organization International Classification of Diseases (herein: “ICD-11”), e.g., general anxiety, panic, social phobia, social anxiety, separation anxiety, secondary anxiety, stress- related insomnia, and others. Usually, treating the condition comprises administering to a patient in need thereof, of the composition in a daily dose of between 3.5 g and 10.0 g of x5 concentrated extracts as described below, in divided doses at a regimen of between once daily and four times daily.

[0014] In a further aspect, provided herein a method of manufacturing of a composition suitable for use in treating a condition associated with stress and / or anxiety, said method comprising providing ingredients comprising traditional Chinese remedies, said ingredients being as defined herein, combining said ingredients together; and mixing said ingredients to obtain a homogenous mixture. The method may further comprise filling the obtained homogenous mixture into capsules.

[0015] Thus, the compositions according to some embodiments of the present invention comprise at least seven different ingredients of the total twelve ingredients listed in Tables 2 and3. Preferably, the composition may comprise ten ingredients enumerated in Table 4. Further, the compositions may comprise the ingredients in amounts as enumerated as designated in Table 5.

[0016] Thus, in a first aspect provided herein a composition useful for management of an anxiety and / or a stress-related disorder and symptoms thereof, comprising traditional Chinese remedies’ ingredients, said ingredients comprise Semen Ziziphus Jujubae, Radix Paeoniae Lactiflorae, Radix Bupleurii Falcati, Radix Salviae Miltiorrhizae, Radix Angelicae Sinensis, Fructus Schisandrae Chinensis, and Sclerotum Wolfiporiae Extensae, wherein said ingredients comprise between 60 and 100% by weight of said composition. The composition may be further comprising at least one of Radix Ophiopogoni Japonicae, Fossilus Ossis Dracoinii, Radix Panagis Ginsengi, Radix Polygalae Tenuifoliae, and Radix Saussureae Costi. The composition according to any one of the preceding claims, comprising Semen Ziziphus Jujubae, Radix Paeoniae Lactiflorae, Radix Salviae Miltiorrhizae, Radix Bupleurii Falcati, Radix Angelicae Sinensis, Sclerotum Wolfiporiae Extensae, Radix Polygalae Tenuifoliae, Radix Ophiopogoni Japonicae, Radix Panagis Ginsengi, and Fructus Schisandrae Chinensis. The composition may also be wherein each of said ingredients constitute between 2% and 20% of the total weight of the composition, given as 100% by weight. The composition may thus be comprising between 10 and 22 parts by weight Semen Ziziphus Jujubae, between 5 and 18 parts by weight Radix Paeoniae Lactiflorae, between 3 and 12 parts by weight Radix Bupleurii Falcati, between 6 and 15 parts by weight Radix Salviae Miltiorrhizae, between 3 and 15 parts by weight Radix Angelicae Sinensis, and between 0.5 and 10 parts by weight Fructus Schisandrae Chinensis, between 9 and 15 parts by weight Sclerotum Wolfiporiae Extensae. The composition may be further comprising between 3 and 10 parts by weight Radix Polygalae Tenuifoliae, between 6 and 15 parts by weight Radix Ophiopogoni Japonicae, between 15 and 30 parts by weight Fossilus Ossis Draconii, between 3 and 10 parts by weight Radix Panagis Ginsengi, and / or between 2 and 10 parts by weight Radix Saussureae Costi. The composition may also be comprising about 20 parts by weight Semen Ziziphus Jujubae, about 15 parts by weight Radix Paeoniae Lactiflorae, about 10 parts by weight Radix Bupleurii Falcati, about 10 parts by weight Radix Salviae Miltiorrhizae, about 10 parts by weight Radix Angelicae Sinensis, about 10 parts by weight Sclerotum Wolfiporiae Extensae, about 10 parts by weight Radix Polygalae Tenuifoliae, about 12 parts by weight Radix Ophiopogoni Japonicae about 10 parts by weight Radix Panagis Ginsengi, and about 10 parts byweight Fructus Schisandrae Chinensis. The composition may also be consisting essentially of Semen Ziziphus Jujubae, Radix Paeoniae Lactiflorae, Radix Salviae Miltiorrhizae, Radix Bupleurii Falcati, Radix Angelicae Sinensis, Sclerotum Wolfiporiae Extensae, Radix Polygalae Tenuifoliae, Radix Ophiopogoni Japonicae, Radix Panagis Ginsengi, and Fructus Schisandrae Chinensis, optionally wherein each of said ingredients constitute between 5% and 20% of the total weight of the composition, given as 100% by weight. The composition may this be consisting essentially of about 20 parts by weight Semen Ziziphus Jujubae, about 15 parts by weight Radix Paeoniae Lactiflorae, about 10 parts by weight Radix Bupleurii Falcati, about 10 parts by weight Radix Salviae Miltiorrhizae, about 10 parts by weight Radix Angelicae Sinensis, about 10 parts by weight Sclerotum Wolfiporiae Extensae, about 10 parts by weight Radix Polygalae Tenuifoliae, about 12 parts by weight Radix Ophiopogoni Japonicae about 10 parts by weight Radix Panagis Ginsengi, and about 10 parts by weight Fructus Schisandrae Chinensis. The composition may also be wherein said ingredients are provided in any one of following forms: according to traditional Chinese compounding practice, as concentrated extracts, as an aqueous extract, as an organic extract, as a standardized extract, as a tincture, or as a dried extract. The composition may also be wherein said ingredients are provided in a form of concentrated extracts, preferably wherein the concentration factor is between x3 and x7. The composition may also be filled into a pharmaceutically acceptable capsule. The composition may also be in a form of a liquid extract, optionally wherein said liquid extract is characterized by the concentration factor of between x3 and x7, further optionally of x5. The composition may also be wherein said liquid extract contains an equivalent dose of between 1 and 5 gram-equivalents of dried plant material per milliliter, optionally 2.5 gram-equivalents per milliliter.

[0017] In a further aspect provided herein a composition as defined herein, for use in the treating of a condition characterized by anxiety or stress. The composition may be wherein said condition is selected from the group consisting of general anxiety symptoms (MB24.3), general anxiety disorder (6B00), panic (MB23.H) and panic disorder (6B01), agoraphobia (6B02), social anxiety disorder (6B04), separation anxiety disorder (6B05), and a secondary anxiety, as defined in 11threvision of World Health Organization International Classification of Diseases. The composition may also be wherein said condition characterized by anxiety or stress is selected from the group consisting of general anxiety, anxiety attacks, post-traumatic syndrome, depression,mood swings, panic, and stress-induced attention deficit. The composition may be wherein said treating comprises administering to a patient in need thereof of the composition as x5 concentrated extracts in a dose of between 3.0 g and 10.0 grams, at a regimen of between once daily and four times daily. The composition may be wherein said treating comprises administering to a patient in need thereof of the composition as x5 concentrated extracts in a dose of between 4.0 and 8.5 grams per day or an equivalent thereof in other component form, in three divided doses. The composition may be wherein said treating comprises administering to a patient in need thereof of the composition as x5 concentrated liquid extracts in a dose of between be between 6 and 20 milliliters per day in other component form, optionally between 8 and 12 mL per day, in two divided doses, or between 12 and 18 mL per day in three divided doses.

[0018] In a further aspect provided herein a method of manufacturing of a composition suitable for use in treating a condition associated with anxiety and / or stress, said method comprising: providing ingredients comprising botanical or mineral material, said ingredients being as defined herein; combining said ingredients together; and mixing said ingredients to obtain a homogenous mixture. The method may be further comprising filling said homogenous mixture into a capsule, or providing said homogenous mixture in a liquid-dispensing bottle. The method may be further comprising packaging finished composition in a suitable package, and providing an oral or written instruction on the administration of the composition.DETAILED DESCRIPTION

[0019] In the first aspect, provided herein compositions that may be useful for treatment of conditions related to stress and / or anxiety. In a further aspect provided herein methods of making such compositions. In a yet further aspect provided herein methods of treatment of patients in need thereof, using such compositions, as well as using the compositions for the treating of patients in need thereof.

[0020] As can be readily seen in Table 1 above, despite the very different compositions there are but a few remedies that they share in common. These include, for example, bat zhu, fit ling, ren shen, and yuan zhi. Additionally, some of the known formulas, e.g., JWXYS andTWBXD, share only two components, understandably, as they are intended for treatment of completely different root cause.

[0021] It has now been unexpectedly found that combinations of suan zao ren, bai shao, chai hu, dan shen, dang gui, fu ling, and wu wei zi, may be particularly beneficial in the management of anxiety and / or stress-related conditions, with a very broad underlying etiology. Although it may be noted that the combination bears some resemblance to JWXYS and TWBXD, it is materially different from both. First, it is different from JWXYS in that it does not require several prominent components, such as bai zhu, bo he, sheng jiang, and zhi gan cao. It is also different from TWBXD that it does not require the presence of a major component thereof - of sheng di huang (Rehmannia glutinosa). The compositions as presently disclosed preferably also comprise mai men dong, mu xiang, yuan zhi, long gu, and / or ren shen. In currently preferred embodiments, the composition comprises, or consists essentially of, suan zao ren, bai shao, chai hu, dan shen, dang gui, fu ling, yuan zhi, mai men dong, ren shen, and wu wei zi, the ten components enumerated in Table 4 (the “10-formula”).

[0022] Thus, in a first aspect of the present invention, disclosed herein are useful compositions of herbal components, e.g., in form of traditional Chinese remedies, that, when administered to a patient in need thereof, e.g., a human or a non-human mammal, have a beneficial effect. Usually, upon administration of the composition to the patient reduces the symptoms and feeling associated with stress and / or anxiety. As a result, such compositions are useful for management of conditions resulting from or involving stress and / or anxiety. Whereas the exact mechanism of action of the composition or of the components thereof is not knows or material, without being bound by a particular theory it is believed that the administration of the composition may directly reduce the central noradrenergic, serotonergic, and / or gabaergic disbalance, and / or directly affect the peripheral sympathetic nervous system to ameliorate the symptoms and / or the underlying processes of general anxiety. It has been surprisingly found that combining specific herbal components it may be possible to achieve an improved stress / anxiety control, relatively to existing compositions, that are not tied specifically to other underlying or comorbid conditions.

[0023] Preferably, the subject is a human, or a non-human animal, in particular a non- human mammal. The composition may be useful for treating anxiety and / or stress-relatedconditions in the subject. The conditions include but not limited condition characterized by stress and / or anxiety, generally classified in a subclass 06 or 07 of the 11threvision of World Health Organization International Classification of Diseases (herein: “ICD-11”), e.g., general anxiety symptoms (ICD-11 MB24.3), general anxiety disorder (ICD-11 6B00), panic (ICD-11 MB23.H) and panic disorder (ICD-11 6B01), social phobia (i.e., agoraphobia, ICD-11 6B02), social anxiety disorder (ICD-11 6B04), separation anxiety disorder (ICD-11 6B05), stress-related insomnia, secondary anxiety symptoms, and others. The composition may be administered to prevent the ailment, i.e., the composition may be administered prophy lactically to prevent the development of an anxiety, particularly in subjects falling under one or more risk factors for developing stress and / or anxiety, e.g., a subject involved in an activity anticipating elevated stress level. In some preferred embodiments, condition characterized by anxiety or stress may be selected from the group consisting of general anxiety, anxiety attacks, post-traumatic syndrome, depression, mood swings, panic, and stress-induced attention deficit.

[0024] Thus, the compositions of the present disclosure herein comprise at least seven different ingredients of the twelve ingredients enumerated in Tables 2 and 3. In preferred embodiments the composition comprises suan zao ren (Semen Ziziphus Jujubae), bai shao (Radix Paeoniae Lactiflorae), chai hu (Radix Bupleurii Falcati), dan shen (Radix Salviae Miltiorrhizae), dang gui (Radix Angelicae Sinensis), fit ling (Sclerotum Wolfiporiae Extensae), and wu wei zi (Fructus Schisandrae Chinensis). In some further preferred embodiments, the composition further comprises any one of mai men dong (Radix Ophiopogoni Japonicae), and / or long gu (Fossilus Ossis Dracoinii), and / or mu xiang (Radix Saussureae Costi), yuan zhi (Radix Polygalae Tenuifoliae), and / or ren shen (Radix Panagis Ginsengi), and preferably at least three of the above, as explained below.

[0025] Although the preferred compositions comprise all ten ingredients enumerated in Table 4, the partial compositions with less than ten components, i.e., the 7-Formula, with or without the additional components enumerated in Table 3, demonstrate the principles of formulating the composition. Thus, in one preferred embodiment the composition comprises bai shao (Radix Paeoniae Lactiflorae), chai hu (Radix Bupleurii Falcati), dan shen (Radix Salviae Miltiorrhizae), dang gui (Radix Angelicae Sinensis), / ? / Z / / ?g(Sclerotum Wolfiporiae Extensae), mai men dong (Radix Ophiopogoni Japonicae), ren shen (Radix Panagis Ginsengi), suan zao ren(Semen Ziziphus Jujubae), wu wei zi (Fructus Schisandrae Chinensis), and yuan zhi (Radix Polygalae Tenuifoliae). The relative amounts of each ingredient in the formula may vary as known in the art and as described in greater detail below, but generally each ingredient may typically constitute between 0.5% and 30%, preferably between 2% and 20% by weight, of the total weight of the composition, given as 100%. Naturally, when the composition comprises only the 7-formula, the relative amounts may be proportionally higher, e.g., in the upper portion of the general range above.

[0026] These ingredients typically comprise between 60 and 100% by weight of the composition, e.g., between 65 and 100%, or between 70 and 100%, or between 75 and 100%, or between 80 and 100%. Within the totality of the ingredients, the composition may comprise between 10 and 22 parts by weight suan zao ren (Semen Ziziphus Jujubae), between 5 and 18 parts by weight bai shao (Radix Paeoniae Lactiflorae), between 3 and 12 parts by weight chai hu (Radix Bupleurii Falcati), between 6 and 15 parts by weight dan shen (Radix Salviae Miltiorrhizae), between 3 and 15 parts by weight danggui (Radix Angelicae Sinensis), between 9 and 15 parts by weight fu ling (Sclerotum Wolfiporiae Extensae), and between 0.5 and 10 parts by weight wu wei zi (Fructus Schisandrae Chinensis). Further, if used, the composition may comprise between 6 and 15 parts by weight mai men dong (Radix Ophiopogoni Japonicae), between 3 and 10 parts by weight ren shen (Radix Panagis Ginsengi), and / or between 3 and 10 parts by weight yuan zhi (Radix Polygalae Tenuifoliae), between 15 and 30 parts by weight long gu (Fossilus Ossis Dracoinii) and / or between 2 and 10 parts by weight mu xiang (Radix Saussureae Costi). The final percentage of each compound is dependent on the number of components and total number of parts by weight, with the partial weight of the component being divided by the total weight of the composition. These relative amounts may thus vary as described herein, but generally each ingredient may typically constitute between 2% and 20% of the total weight of the composition, given as 100%, e.g., between 5% and 20%, or a proportionally lower fraction if the totality of these ingredients does not constitute 100% but less, i.e., between 60% and 100%, as described above. The composition is then administered as further described herein.

[0027] According to further principles, sometimes the components may be substituted for other components, with similar traditional action, but with increased or decreased potency. For example, suan zao ren may be at least partially substituted for bai zi ren 5-10 parts by weight orda zao (Fructus Jujubae) in a dose of 5-10 parts by weight, preferably about 10 parts by weight. Bai shao may be at least partially substituted for sheng di huang in a dose of 10-30 parts by weight, preferably about 15 parts by weight, or for chi shao in a dose of 5-10 parts by weight, preferably about 10 parts by weight. Chai hu may be at least partially substituted for xiang fit (Rhizoma Cyperi) in a dose of 5-12 parts by weight, preferably about 10 parts by weight, or for yu jin (Radix Curcumae) in a dose of 5-10 parts by weight, preferably about 10 parts by weight. Dan shen may be at least partially substituted for mu dan pi (Cortex Moutani) in a dose of 6-12 parts by weight, preferably about 10 parts by weight. Danggui may be at least partially substituted for chuan xiong in a dose of 5-10 parts by weight, preferably about 10 parts by weight. Fu ling may be at least partially substituted for fu shen in a dose of 10-15 parts by weight, preferably about 10 parts by weight, or for lu hui (Aloe Vera) in a dose of 0.5-1.5 parts by weight, preferably about 1 part by weight. Wu wei zi may be at least partially substituted for Han zi (Semen Nelumbinis) in a dose of 5-12 parts by weight, preferably about 10 parts by weight, or for mu li (Concha Ostreae) in a dose of 10-30 parts by weight, preferably about 20 parts by weight. Preferably, no more than two substitutions as described herein may be made in the composition comprising 7 components.

[0028] Likewise, mai men dong may be at least partially substituted for bai he (Bulbus Lilii) in a dose of 10-30 parts by weight, preferably about 10 parts by weight, or in non-pregnant patients for tian hua fen (Radix Trichosanthis) in a dose of 10-15 parts by weight, preferably about 10 parts by weight. Ren shen may be at least partially substituted for tai zi shen (Radix Pseudostellariae) in a dose of 5-15 parts by weight, preferably about 10 parts by weight, or for huang qi in a dose of 10-30 parts by weight, preferably about 15 parts by weight. Yuan zhi may be at least partially substituted for huang lian (Rhizoma Coptidis) in a dose of 2-10 parts by weight, preferably about 10 parts by weight, or for mu tong (Caulis Akebiae) in a dose of 5-10 parts by weight, preferably about 10 parts by weight. Similarly preferably, no more than three substitutions as described herein may be made in the composition comprising 10-12 components.

[0029] These relative amounts may vary as well, as described above, but generally each ingredient may typically constitute between 0.5% and 25% of the total weight of the composition, given as 100%, or proportionally lower fraction if the totality of these ingredients does not constitute 100% but less, i.e., between 60% and 100%, as described above. Most preferably, therelative amounts of each ingredient are as readily understood from the compositions and relative weights as described herein.

[0030] The composition may comprise all ten ingredients enumerated in table 4, or their respective substitutes, as described above. When the composition comprises all ten ingredients, without being bound by any particular theory it is believed that the composition is particularly balanced and suitable for long-term treatment, without excessive effects on any of the traditional axes. The composition may thus be successfully used for extended time intervals. In the embodiments when the composition comprises the ten ingredients, it may be comprising about 20 parts by weight, e.g., between 18 and 22 parts by weight of suan zao ren (Semen Ziziphus Jujubae), about 15 parts by weight, e.g., between 13 and 17 parts by weight of bai shao (Radix Paeoniae Lactiflorae), about 10 parts by weight, e.g., between 8 and 12 parts by weight of chai hu (Radix Bupleurii Falcati), about 10 parts by weight, e.g., between 8 and 12 parts by weight of dan shen (Radix Salviae Miltiorrhizae), about 10 parts by weight, e.g., between 8 and 12 parts by weight of dang gui (Radix Angelicae Sinensis), about 10 parts by weight, e.g., between 9 and 12 parts by weight of fit ling (Sclerotum Wolfiporiae Extensae), about 10 parts by weight, e.g., between 7 and about 10 parts by weight of yuan zhi (Radix Polygalae Tenuifoliae), about 12 parts by weight, e.g., between 10 and 15 parts by weight of mai men dong (Radix Ophiopogoni Japonicae), about 10 parts by weight, e.g., between 7 and about 10 parts by weight of ren shen (Radix Panagis Ginsengi), and about 10 parts by weight, e.g., between 7 and about 10 parts by weight of wu mei zi (Fructus Schisandrae Chinensis).

[0031] The disclosed compositions may constitute between 60 and 100% by weight of the composition. Although the balance may contain additional traditional Chinese or other herbal or mineral remedies, provided they do not constitute more that 0-40 percent by weight, normally the compositions do not require any further traditional Chinese remedies beyond the combinations as disclosed herein. However, they may contain minor component that do not significantly affect its activity and efficacy, i.e., the compositions may be consisting essentially of the enumerated ingredients. The composition may also further comprise inactive components, as may be needed and required for the preparation. Thus, in some embodiments, the composition may consist essentially of about 20 parts by weight, e.g., between 18 and 22 parts by weight of suan zao ren (Semen Ziziphus Jujubae), about 15 parts by weight, e.g., between 13 and 17 parts by weight ofbai shao (Radix Paeoniae Lactiflorae), about 10 parts by weight, e.g., between 8 and 12 parts by weight of chai hu (Radix Bupleurii Falcati), about 10 parts by weight, e.g., between 8 and 12 parts by weight of dan shen (Radix Salviae Miltiorrhizae), about 10 parts by weight, e.g., between 8 and 12 parts by weight of dang gui (Radix Angelicae Sinensis), about 10 parts by weight, e.g., between 9 and 12 parts by weight of fit ling (Sclerotum Wolfiporiae Extensae), about 10 parts by weight, e.g., between 7 and about 10 parts by weight of yuan zhi (Radix Polygalae Tenuifoliae), about 12 parts by weight, e.g., between 10 and 15 parts by weight of mai men dong (Radix Ophiopogoni Japonicae), about 10 parts by weight, e.g., between 7 and about 10 parts by weight of ren shen (Radix Panagis Ginsengi), and about 10 parts by weight, e.g., between 7 and about 10 parts by weight of wu mei zi (Fructus Schisandrae Chinensis). Thus, the general composition is summarized in the Table 5 below.Table 5

[0032] The compositions may further comprise additional suitable herbs or minerals e.g., to accommodate specific personal traits, as known in the Chinese medicine. The additional components may sometimes be selected from the components enumerated in the Table 1 above. The amounts of these additional ingredients are determined by the needs of the patient and include any applicable amount by weight as known in the Chinese medicine. Generally, the relative amounts are such that the amount of each of the ingredients between 1.5% and 70% by weight of the composition, provided that the total sums up to 100%. Preferably, the relative amounts of theseingredients may be between 2% and 20 % by weight. The relative amounts of each ingredient will be dependent on the ingredient potency and form, and collaborative traditional action within the combination, as described, inter alia, in Chinese Herbal Formulas, Treatment Principles and Composition Strategies, by Yifan Yang, 2010, at Elsevier Press, ISBN: 9780702031328.

[0033] The Chinese traditional remedies usually refer to botanical or mineral component, but the traditional names also usually refer to the particular way these botanical or mineral components are obtained and prepared. Apart from the specific botanical part of a botanical remedy, the name usually also implies that the component was harvested from a specific plant, the material has been obtained from a specific plant organ, was audited for the classical description of appearance, color, taste, odor, and other traditional tests, and then optionally prepared according to the traditional way, such as dried and ground, boiled in water, cooked in honey, or otherwise modified according to the Chinese medical tradition. Similarly, mineral remedies are audited for the appearance, color, particle size, etc. Therefore, most preferably, the names of all traditional Chinese remedies refer to the “compendial” forms of the remedies, prepared according to the rules of the traditional Chinese medical compounding. As available today, the official forms of the Chinese traditional remedies may come as concentrated extracts, i.e., particularly the botanical material is supplied in a form that is substantially devoid of cellulose and other structural components. The concentrated extracts may be expressed in terms of their respective increased potency, e.g., x3, x4, x5, x6, or x7, although concentrations of up to xlO may be possible. The optimal concentration for each individual component is dependent on the component and the concentration process thereof, and the preferred concentration may therefore vary for each component mutatis mutandis.

[0034] Foregoing notwithstanding, in some embodiments, at least some of the herbal components of the compositions as described herein may be present in conventional herbal form as known in the Western medicine, i.e., as an aqueous or organic extract, tincture, dried extracts, standardized extracts, and the like. Each of the components may be present in a suitable form, and some of the components of the composition may be present, e.g., as aqueous extract, whereas some others may be in traditional forms, or as dried organic extract, etc.

[0035] The composition any further comprise any pertinent quantity of inactive components, e.g., inert excipients, which may be used to facilitate formulating the composition to a suitable administrable form, e.g., as known in the art. Particularly, a composition may be adapted for oral administration, e.g., as concentrated liquid composition, or as dried-extract (optionally concentrated) filled capsules.

[0036] The composition may usually be a pharmaceutical composition or a nutraceutical composition. The composition may also be provided in a form of a food additive or a dietary supplement.

[0037] As described below, the usual dose of the composition may be dependent on the components of the composition, but may usually be between 3.0 g and 10.0 grams when the composition is provided as a mixture of the x5 concentrated traditionally compounded remedies. Thus, when the component are present as dried plants, the dose may be between 15 and 50 grams per day. Therefore, the composition may preferably be provided as concentrated extracts of the composition or of the individual components thereof, whereby the dose may be significantly reduced. The preferred single daily dose of the composition administered as x5 concentrate may be between 4.0 and 8.5 grams per day. When the composition is presented as a liquid extract, it may be dosed according to the same dosing principles based on the equivalent dose of the dried plant material. For example, when a liquid extract, e.g., a tincture, contains an equivalent dose of 2.5 g of dried plant material in 1 milliliter, the dose may be between 6 and 20 milliliters per day (equivalent to 15-50 grams of dried plant material). It ought to be borne in mind that the liquid extract containing, for the sake of demonstration, an equivalent dose of 2.5 g of dried plant material in 1 milliliter, does not in fact contains 2.5 g of material per each milliliter, rather it contains extracted components concentrated from 2.5 g of dried plant material.

[0038] The daily dose of the composition may be administered in a suitable regimen. The regimen is preferably dividing the dose in three individual administrations, such that a third of a daily dose is administered three times a day, or t.i.d., as known in prescription terminology. Alternatively, the dose may be administered divided in half and given twice daily, or b.i.d. The daily dose may also be divided in quarters and administered in four administrations during the day, i.e., four times daily, q.i.d. The multiple administrations are preferably achieved by instructing thepatients to maintain a roughly equal time intervals between the doses, that is, the b.i.d. may be given roughly every 12 hours, t.i.d. may be given roughly every eight hours, and q.i.d. may be given roughly every six hours. Alternatively, in some cases the whole daily dose may be administered ay once, that is, in once-daily administration, or qd, as known in prescription terminology.

[0039] As explained above, when a liquid extract containing an equivalent dose of 2.5 g of dried plant material in 1 milliliter, the dose may be between 6 and 20 milliliters per day. The dose may be given, for example, as 3-6 mL 2-3 times daily, e.g., 3 mL b.i.d., 4 mL b.i.d., 5 mL b.i.d., 6 mL b.i.d., 3 mL t.i.d., 4 mL t.i.d., 5 mL t.i.d., or 6 mL t.i.d. Preferably, when the patient is an adult, the dose is 5 mL b.i.d. or t.i.d. Additionally, in milder cases, a once-daily administration may be sufficient. In these cases the dose may be between 3 to 10 mL qd, e.g., 3 mL qd, 4 mL qd, 5 mL qd, 6 mL qd, 7 mL qd, 8 mL qd, 9 mL qd, or 10 mL qd. Likewise, any amount including fractional volume between any of the indicated dosages could be possible if the case prescribes slow titration. Preferably, the dose may be between 8 and 12 mL of the composition per day, in two divided doses, e.g., 5 mL b.i.d. Also preferably, the dose may be between 12 and 18 mL per day, in three divided doses, e.g., 5 mL t.i.d.

[0040] A composition according to the teaching herein may be a pharmaceutical composition. The suitable pharmaceutical dosage forms of the composition are preferably oral administrable dosage form. These include a liquid, e.g., a solution comprising soluble extracts of the composition components, a tincture of the composition components, a dispersion of the soluble and insoluble composition components, e.g., a colloidal dispersion or a coarse dispersion, and an elixir. Preferably, the dosage form is a liquid, e.g., a tincture or liquid concentrated extracts, or a solid dosage form, e.g., a tablet or a capsule, comprising the solid components of the composition. The dosage form may also be in a form of a gel-cap, e.g., comprising oil-soluble / dispersible components of the composition. In some embodiments, the composition is a nutraceutical composition or a food additive.

[0041] Thus, the dosage form may be a capsule. The capsule may be filled with the composition of the formula components, homogenously blended together. The filling blend may then further comprise a filler, e.g., lactose or microcrystalline cellulose, a lubricant, e.g.m a fattyacid or its salt, like magnesium stearate, a disintegrant, e.g., croscarmelose, crospovidone, or sodium starch glycolate, a glidant, e.g., colloidal silicon dioxide, an antioxidant, an antimicrobial preservative, a colorant, and / or a fragrance. The components may be granulated, e.g., to improve the flow properties of the powder. In these embodiments the composition may further comprise a binder, e.g., a povidone, a hypromellose, a methylcellulose, a hydroxypropyl cellulose, or an ethyl cellulose. The capsule may then be coated with an immediate-release sealing coating, e.g., of Opadry™ family, such as hypromellose or polyvinyl-alcohol-based coating.

[0042] Alternatively, the dosage form may be a tincture, e.g., a liquid extract. In some preferred embodiments, the liquid extract may be based on a hydroalcoholic mixture, e.g., contain between 20 and 50 % by volume of ethanol in water, e.g., between 30% and 40%. The liquid extracts may have a concentration of between 1 g-equivalent / mL and 5 g-equivalent / mL of dried plant material equivalent, as elaborated above. Preferably, the extracts may have a concentration of between 2 g-eq / mL and 3 g-eq / mL of dried plant material equivalent, e.g., between 2.3 and 2.7 g-eq / mL.

[0043] The composition and a dosage form as described herein may be made using processes well known in the art, e.g., by conventional pharmaceutical and food technology processes. Some of these techniques are described, inter alia, in Remington: The Science and Practice of Pharmacy, by Pharmaceutical Press (ISBN 978-0-85711-062-6), also known as “Remington’s Pharmaceutical Sciences”.

[0044] Generally, the compositions are manufactured by combining together the components of the composition. Dosage forms may then be manufactured by combining the composition with the components of the dosage forms.

[0045] The components are usually weighed with the required accuracy, e.g., depending on the scale, and mixed together. The components may be first ground to a fine powder prior to combining with other components. Alternatively, the weighed components may be advantageously ground together to provide a homogenous fine powder of the composition. The grinding may usually be performed as known in the art, e.g., using a suitable mill. The mill may preferably be a blade mill, but may also be a rotor mill, a hammer mill, a ball mill, and the like. The componentsmay be likewise supplied in free-flowing powder form. The composition may also be granulated according to the needs, if particles with uniform size larger than e.g., 50 microns may be required, for example for capsule filling. The granulation may be performed using conventional granulators, e.g., high-shear granulators. Binders and / or granulation liquid may be added to the blend during the granulation. The wet granulation may then be dried, e.g., in tray oven, or in a fluid bed drier. Dried granulation may be performed, e.g., by roller compaction and subsequent grinding to desired particle size. The dried granulation may then be further ground using a mill to a desired particle size. The additional components may then be added and blended. Blending may be carried out using a variety of equipment, e.g. tumblers, mixers, for a time sufficient to produce a homogenous blend. When the composition is provided into an edible article, it may be combined first with a liquid that is present in the recipe, e.g., an oil. Some of the components may be pre-processed, e.g., protected or capsulated, before blending. The final blend may be filled in suitable capsules, e.g., pharmaceutical capsules of a standard size of between 0 to 00E.

[0046] The finished composition may then be further packaged in a suitable package, e.g., a plastic bottle or other suitable container. Preferably, the packaged composition is accompanied by an oral instruction to the patient in need thereof or to a caregiver thereof, on the administration of the composition, by affixing a written instruction on the administration onto the package, or both.

[0047] Various other features according to the invention as described herein for the aspect of compositions and / or dosage forms are applicable mutatis mutandis to the methods of manufacturing of the composition according to the teachings herein.

[0048] The composition may be used for treating a subject in need thereof. Particularly, the compositions may be used to treat a subject suffering from anxiety and / or stress-related disorder as elaborated above, or a subject who is susceptible to suffering from anxiety and / or stress, i.e., a subject having one or more of known risk factors for development of the condition or being exposed to anticipatory situation wherein anxiety and / or stress may ensue. Preferably, the subject is a human, although in some embodiments the subject may be a non-human animal, in particular a non-human mammal. Thus, also provided herein a method of treating a subject in need thereof, said subject suffering from anxiety and / or stress-related disorder as elaborated above, or a subjectwho is susceptible to suffering from anxiety and / or stress, as defined herein, by administering to said subject a therapeutically effective dose of a composition as generally described herein.

[0049] In some embodiments, administering the composition comprises administering a dosage form comprising the composition. The administering is usually performed according to the desired dose at a desired regimen.

[0050] The particular dosage administered is any suitable dosage and can be determined by a practitioner, e.g., based on factors such as the weight of the subject, and / or the severity of the condition being treated. It is currently believed that the required dosage for an adult human suffering from an anxiety symptoms or excessive stress may be between 3.0 and 10.0 grams per day of x5 concentrated dry remedies, preferably between 4 and 8.5 grams. The dose for the liquid extracts may be readily determined based on the dry content in the extract; generally, when standardized liquid extracts are used, the dose may be between about 6 and about 20 mL per day, preferably between about 7 and about 16 mL per day, e.g., 10 mL per day in two divided doses, between 12 and 18 ml per day, e.g., 15 mL in three divided doses.

[0051] In some such embodiments, the administering by oral administration of the composition to the subject constitutes treating the condition of the subject. Preferably, the treatment leads to alleviation of the stress and / or relieving or resolving of the anxiety. In some embodiments, the treatment leads to prevention of the development or deterioration of the stress and / or anxiety. Thus, the composition may be used for prophylaxis of anxiety and / or stress -related disorders in a patient in need thereof, e.g., in a patient at risk of developing anxiety and / or stress- related disorders, e.g., due to an existing or suspected risk factor. As demonstrated in the appended examples, when the 10-formula composition was used to alleviate the symptoms of patients suffering from anxiety and stress disorders, a significant reduction of the symptoms was recorded on the follow-up, including ina patient with treatment-refractory post-traumatic stress disorder.

[0052] Various other features according to the invention as described herein for the aspect of compositions and / or dosage forms are applicable mutatis mutandis to the methods of treating anxiety and / or stress-related disorders by the composition according to the teachings herein. Generally, various other features according to the invention as described herein for one aspect areapplicable mutatis mutandis to other disclosed aspects according to the teachings herein. The herein described preferred embodiments provided herein demonstrating some of the embodiments of the present disclosure are provided to better understand the present disclosure, which however does not limit the invention in any respect. Some variants and equivalents may be readily envisaged by the skilled artisan; the invention therefore encompasses all these variations and equivalents. It must also be noted that, as used in this specification and the appended claims: all scientific and technical terms have meanings commonly used in the art unless otherwise specified; the definitions as provided herein are given with the purpose to facilitate understanding of certain terms used frequently herein and are not necessarily meant to limit the scope of the present disclosure; as used herein the term "about", “c.a.”, and like, as used interchangeably herein, refers to the value and the range of ± 10 %; the terms "comprises", "comprising", "includes", "including", "having" and their conjugates mean "including but not limited to", with this terms also encompassing the terms "consisting of' and "consisting essentially of', which have their narrower meaning as known in the art, thus an embodiment described as comprising something also discloses embodiments consisting essentially of same and consisting exclusively of same; the singular forms “a”, “an”, and “the”, include plural referents unless the content clearly dictates otherwise; as used herein, a phrase in the form “A and / or B” means a selection from the group consisting of (A), (B) or (A and B); as used herein, a phrase in the form “at least one of A, B, and C” means a selection from the group consisting of (A), (B), (C), (A and B), (A and C), (B and C) or (A, and B, and C), and further combinations are envisaged for the lists comprising larger number of terms. It is appreciated that, certain features of the invention, which are, for brevity, described in the context of separate embodiments, may also be provided in combination with other features in a single embodiment, unless technically infeasible. Conversely, features described in specific combinations of various features, which are, for clarity and demonstration, are described in the context of a single embodiment, may also be provided as separate embodiments individually or in any suitable subcombination with other features and / or embodiments, as reasonable to the skilled artisan, suitable and operative. Certain features described in the context of various embodiments, including preferred features, are not to be considered essential features of those embodiments, unless the embodiment is inoperative without those elements.T1EXAMPLESExample 1: The composition

[0053] A composition according to the teachings herein was made by providing 100 g of mixture of the ten ingredients (each ingredient was purchased separately as x5 concentrate from audited reliable sources in Israel) at the (w / w) percentage as specified in table 5 by mixing the separate ingredients together in a blade blender. The resulting fine homogeneous-looking powder was an embodiment of a composition according to the teachings herein.Table 6Example 2: prospective efficacy study

[0054] The effect of the Composition according to Example 1 has been tested on informed patients of certified Chinese medicine clinic, referring due to underlying condition characterized by anxiety or stress.

[0055] A total of 19 patients provided consent to try the treatment with the composition according to Example 1. The volunteers were 12 males and 7 females, aged between 18 and 69 (mean ± SD: 48±17.0 years, median 54 years). The volunteers suffered in general from at least one of bothersome general anxiety and stress symptoms (n=6), anxiety attacks (n=6), post-traumaticsyndrome (n=2), moodiness and mood swings (n=2), depression (n=l), panic (n=l), and stress- induced attention deficit (n=l). The mean severity of symptoms upon admission was between 1 and 6 (mean ±SD 4.53±1.17), on a scale between 1 and 6, with 1 being slight discomfort and 6 being almost intolerable symptoms.

[0056] Nine of the patients received various prior treatments, both conventional and wholistic, as enumerated in Table 6 below, and other ten patients referred to the clinic for first line assistance. One further patient continued with medications unrelated to the stress and anxiety.Table 7

[0057] The mean symptom severity score in the previously treated patients was 5±0.7.

[0058] Following obtaining the informed consent, the patients were instructed and agreed to use the provided medication according to instruction. All the patients were instructed to take 5 mL of the x5 -concentrate liquid composition twice daily. The patient started composition as monotherapy or adjunctive to their normal therapy, according to the Table above. Some of the patients controllably reduced the dose of their primary medications under the supervision of prescribing professional.

[0059] The compliance to the treatment was high. Eleven of 19 patients (ca. 58%) reported taking the composition as prescribed, 2 / 19 (10.5%) adhered to the instructions most of the days, 4 / 19 (21%) reported taking the medication once daily on some of the days due to the improvement, and 2 / 19 (10.5%), mostly reporting mild symptoms on admission, reported reducing the medication intake to once daily due to the improvement.

[0060] Upon follow-up, an average improvement of 2.47 ±1.21 score units was reported (range 0-4 score units), to the mean severity score of 2.05 ± 0.91. The paired Student’s T-test furnished p-value of 5.68x10'8, indicating self-reported statistically significant effect of the treatment. This effect may be attributed to the composition of Example 1.

[0061] Particularly noteworthy was 52-y.o. male with treatment-refractory post-traumatic syndrome with multiple failed treatments. Being admitted to the study with the severity score 6, on the follow-up the reported severity score was 2. Three additional patients experiencing frequent anxiety attacks on admission demonstrated similar result without changing the concomitant pharmacotherapy (apart from dose reduction in two patients of three). According to treating professionals, such improvements are unexpected with no added concomitant pharmacotherapy modifications and may be attributed to the composition according to Example 1.

Claims

CLAIMS1. A composition useful for management of an anxiety and / or a stress-related disorder and symptoms thereof, comprising traditional Chinese remedies’ ingredients, said ingredients comprise Semen Ziziphus Jujubae, Radix Paeoniae Lactiflorae, Radix Bupleurii Falcati, Radix Salviae Miltiorrhizae, Radix Angelicae Sinensis, Fructus Schisandrae Chinensis, and Sclerotum Wolfiporiae Extensae, wherein said ingredients comprise between 60 and 100% by weight of said composition.

2. The composition according to claim 1 , further comprising at least one of Radix Ophiopogoni Japonicae, Fossilus Ossis Dracoinii, Radix Panagis Ginsengi, Radix Polygalae Tenuifoliae, and Radix Saussureae Costi.

3. The composition according to any one of the preceding claims, comprising Semen Ziziphus Jujubae, Radix Paeoniae Lactiflorae, Radix Salviae Miltiorrhizae, Radix Bupleurii Falcati, Radix Angelicae Sinensis, Sclerotum Wolfiporiae Extensae, Radix Polygalae Tenuifoliae, Radix Ophiopogoni Japonicae, Radix Panagis Ginsengi, and Fructus Schisandrae Chinensis.

4. The composition according to any one of the preceding claims, wherein each of said ingredients constitute between 2% and 20% of the total weight of the composition, given as 100% by weight.

5. The composition according to any one of the preceding claims, comprising between 10 and 22 parts by weight Semen Ziziphus Jujubae, between 5 and 18 parts by weight Radix Paeoniae Lactiflorae, between 3 and 12 parts by weight Radix Bupleurii Falcati, between 6 and 15 parts by weight Radix Salviae Miltiorrhizae, between 3 and 15 parts by weight Radix Angelicae Sinensis, and between 0.5 and 10 parts by weight Fructus Schisandrae Chinensis, between 9 and 15 parts by weight Sclerotum Wolfiporiae Extensae.

6. The composition according to any one of claims 2-5, further comprising between 3 and 10 parts by weight Radix Polygalae Tenuifoliae, between 6 and 15 parts by weight Radix Ophiopogoni Japonicae, between 15 and 30 parts by weight Fossilus Ossis Draconii, between3 and 10 parts by weight Radix Panagis Ginsengi, and / or between 2 and 10 parts by weight Radix Saussureae Costi.

7. The composition according to any one of preceding claims, comprising about 20 parts by weight Semen Ziziphus Jujubae, about 15 parts by weight Radix Paeoniae Lactiflorae, about 10 parts by weight Radix Bupleurii Falcati, about 10 parts by weight Radix Salviae Miltiorrhizae, about 10 parts by weight Radix Angelicae Sinensis, about 10 parts by weight Sclerotum Wolfiporiae Extensae, about 10 parts by weight Radix Poly galae Tenuifoliae, about 12 parts by weight Radix Ophiopogoni Japonicae about 10 parts by weight Radix Panagis Ginsengi, and about 10 parts by weight Fructus Schisandrae Chinensis.

8. The composition according to any one of the preceding claims, consisting essentially of Semen Ziziphus Jujubae, Radix Paeoniae Lactiflorae, Radix Salviae Miltiorrhizae, Radix Bupleurii Falcati, Radix Angelicae Sinensis, Sclerotum Wolfiporiae Extensae, Radix Polygalae Tenuifoliae, Radix Ophiopogoni Japonicae, Radix Panagis Ginsengi, and Fructus Schisandrae Chinensis.

9. The composition according to claim 8, wherein each of said ingredients constitute between 5% and 20% of the total weight of the composition, given as 100% by weight.

10. The composition according to any one of preceding claims, consisting essentially of about 20 parts by weight Semen Ziziphus Jujubae, about 15 parts by weight Radix Paeoniae Lactiflorae, about 10 parts by weight Radix Bupleurii Falcati, about 10 parts by weight Radix Salviae Miltiorrhizae, about 10 parts by weight Radix Angelicae Sinensis, about 10 parts by weight Sclerotum Wolfiporiae Extensae, about 10 parts by weight Radix Polygalae Tenuifoliae, about 12 parts by weight Radix Ophiopogoni Japonicae about 10 parts by weight Radix Panagis Ginsengi, and about 10 parts by weight Fructus Schisandrae Chinensis.

11. The composition according to any one of the preceding claims, wherein said ingredients are provided in any one of following forms: according to traditional Chinese compounding practice, as concentrated extracts, as an aqueous extract, as an organic extract, as a standardized extract, as a tincture, or as a dried extract.

12. The composition according to any one of the preceding claims, wherein said ingredients are provided in a form of concentrated extracts, preferably wherein the concentration factor is between x3 and x7.

13. The composition according to any one of the preceding claims, filled into a pharmaceutically acceptable capsule.

14. The composition according to any one of the preceding claims, in a form of a liquid extract.

15. The composition according to claim 12, wherein said liquid extract is characterized by the concentration factor of between x3 and x7, optionally of x5.

16. The composition according to any one of claims 14-15, wherein said liquid extract contains an equivalent dose of between 1 and 5 gram-equivalents of dried plant material per milliliter, optionally 2.5 gram-equivalents per milliliter.

17. A composition as defined in any one of the preceding claims, for use in the treating of a condition characterized by anxiety or stress.

18. The composition according to claim 17, wherein said condition is selected from the group consisting of general anxiety symptoms (MB24.3), general anxiety disorder (6B00), panic (MB23.H) and panic disorder (6B01), agoraphobia (6B02), social anxiety disorder (6B04), separation anxiety disorder (6B05), and a secondary anxiety, as defined in 11threvision of World Health Organization International Classification of Diseases.

19. The composition according to any one of claims 17 or 18, wherein said condition characterized by anxiety or stress is selected from the group consisting of general anxiety, anxiety attacks, post-traumatic syndrome, depression, mood swings, panic, and stress-induced attention deficit.

20. The composition according to any one of claims 17 to 19, wherein said treating comprises administering to a patient in need thereof of the composition as x5 concentrated extracts in a dose of between 3.0 g and 10.0 grams, at a regimen of between once daily and four times daily.

21. The composition according to any one of claims 17 to 20, wherein said treating comprises administering to a patient in need thereof of the composition as x5 concentrated extracts in a dose of between 4.0 and 8.5 grams per day or an equivalent thereof in other component form, in three divided doses.

22. The composition according to any one of claims 17 to 21, wherein said treating comprises administering to a patient in need thereof of the composition as x5 concentrated liquid extracts in a dose of between be between 6 and 20 milliliters per day in other component form, optionally between 8 and 12 mb per day, in two divided doses, or between 12 and 18 mb per day in three divided doses.

23. A method of manufacturing of a composition suitable for use in treating a condition associated with anxiety and / or stress, said method comprising: providing ingredients comprising botanical or mineral material, said ingredients being as defined in any one of the preceding claims; combining said ingredients together; and mixing said ingredients to obtain a homogenous mixture.

24. The method according to claim 23, further comprising filling said homogenous mixture into a capsule, or providing said homogenous mixture in a liquid-dispensing bottle.

25. The method according to any one of claims 23 or 24, further comprising packaging finished composition in a suitable package, and providing an oral or written instruction on the administration of the composition.