HERBAL COMPOSITIONS AND METHODS FOR TREATING PREMENSTRUAL SYNDROME

TECHNICAL FIELD

This invention relates to new medicinal compositions and methods for treating premenstrual syndrome and conditions associated therewith. BACKGROUND

Any discussion of the prior art throughout the specification should in no way be considered as an admission that such prior art is widely known or forms part of common general knowledge in the field.

Premenstrual syndrome (PMS) is a set of symptoms which occur at any time before the menstrual period and after ovulation, Le. the latter two weeks of the menstrual cycle. Most commonly PMS is experienced in the weeks or days immediately before the onset of the period. Symptoms include breast swelling or soreness, abdominal pain and /or bloating, mood changes (irritability, depression, anxiety, lability), food cravings, insomnia, headaches, fluid retention and/or lower back pain and digestive disorders.

Different treatments are aimed at different causes of PMS, and different approaches may temporarily relieve some symptoms but not others. Antiinflammatory drugs are helpful for cramping, bowel symptoms, breast pain, and headaches. Anti-anxiety drugs and antidepressants may help with mood, irritability, and concentration. For those women who also seek contraception, contraceptives such as pills, implants and patches (all of which inhibit ovulation) may be of value as they reduce the hormonal variability of the natural menstrual cycle. Supplements help some women as well. A number of treatments mentioned above can produce undesirable or potentially dangerous side-effect and combination therapies may be undesirable. Therefore there is a need for novel therapies for the treatment of PMS and its associated symptoms, that are better tolerated and have fewer side-effects.

It is an object of the present invention to overcome or ameliorate at least one of the disadvantages of the prior art, or to provide a useful alternative.

SUMMARY OF THE INVENTION The formulations of the present invention are designed to provide a treatment for PMS in western women, by improving or alleviating one or more of the symptoms associated with PMS.

According to a first aspect, the present invention provides a composition for prophylactic or therapeutic treatment of PMS, comprising the herbs:

Chai Hu Radix bupleuri Bai Shao Radix paeoniae lactiflorae Dang Gui Radix angelicae sinensis Bai Zhu Rhizoma atractylodes Fu Ling Sclerotium poriae cocos Dan Shen Radix salviae miltiorrhizae He Huan Pi Cortex albizziae julibrissin Xiang Fu Rhizoma cyperi rotundi Xu Duan Radix dipsacus

According to a second aspect, the present invention provides a composition for therapeutic or prophylactic treatment of PMS, comprising the herbs:

Chai Hu Radix bupleuri Bai Shao Radix paeoniae lactiflorae Dang Gui Radix angelicae sinensis Bai Zhu Rhizoma atractylodes Fu Ling Sclerotium poriae cocos Dan Shen Radix salviae miltiorrhizae He Huan Pi Cortex albizziae julibrissin Xiang Fu Rhizoma cyperi rotundi Xu Duan Radix dipsacus and one or more, or all of: Tao Ren Semen persicae Chuan Niu Xi Radix cyathula Yu Jin Radix curcumae

Chong Wei Zi Semen leonuri heterophylli Chuan Xiong Radix ligustici wallichii Hong Hua Carthami flos Chi Shao Radix paeoniae rubra Ji Nei Jin Endothelium corneum gigeraiae galli Tu Si Zi Semen cuscatae Bu Gu Zhi Fructus psoraleae Dang Shen Radix codonopsis pilulosae

Fu Shen Sclerotium poriae cocos

Chen Pi Pericarpium citri reticulate

Gui Zhi Cinnamomum cassia

Qing Pi Pericarpium citri reticulatae viride Suan Zao Ren Semen zizyphi spinosi

Mu Dan Pi Cortex moutan radicis

Yuan Zhi Radix plygalae

Fu Shen Sclerotium poriae cocos

Huang Lian Rhizoma coptidis Gou Teng Ramulus cum unicus uncariae

He Shou Wu Radix polygoni multiflorai

Shan Yu Rou Fructus corni officianalis

Shan Yao Radix dioscorea

Shu Di Radix rehmanniae Zhi Mu Radix anemarrhena

Nu Zhen Zi Fructus ligustri lucidi

Tu Si Zi Semen cuscatae

Mai Ya Fructus hordei

Sheng Jiang Rhizoma zingiberis officinalis Bo He Herba menthae haplocalycis

Gan Cao Glycyrrhiza uralensis

Shi Chang Pu Rhizoma acori tatarinowa

Pu Huang Typhae pollen

Zhi Ke Fructus aurantii Mu Xiang Radix aucklandiae

Wu Yao Radix linderae

Lu Lu Tong Fructus liquidambaris

Huang Qin Radix scuttellariae

Shan Zha Fructus crataegi Zhi Gan Cao Radix glycyrrhiza uralensis

Sheng Ma Rhizoma cimicifugae

Wu Ling Zhi Trogopterori faeces

Sha Ren Amomi fructus

Gui Ban Testudinis plastrum

Ji Xue Teng Caulis spatholobi

Huang Qi Radix astragali

According to a third aspect, the present invention provides a composition for therapeutic or prophylactic treatment of PMS, comprising the herbs: Chai Hu Radix bupleuri

Bai Shao Radix paeoniae lactiflorae

Dang Gui Radix angelicae sinensis and one or more, or all of:

Bai Zhu Rhizoma atractylodes Fu Ling Sclerotium poriae cocos

Dan Shen Radix salviae miltiorrhizae

He Huan Pi Cortex albizziae julibrissin

Xiang Fu Rhizoma cyperi rotundi

Xu Duan Radix dipsacus Tao Ren Semen persicae

According to a fourth aspect, the present invention provides a composition for therapeutic or prophylactic treatment of PMS, comprising the herbs:

Chai Hu Radix bupleuri

Bai Shao Radix paeoniae lactiflorae Dang Gui Radix angelicae sinensis

Bai Zhu Rhizoma atractylodes

Fu Ling Sclerotium poriae cocos

Dan Shen Radix salviae miltiorrhizae and one or more, or all of: He Huan Pi Cortex albizziae julibrissin

Xiang Fu Rhizoma cyperi rotundi

Xu Duan Radix dipsacus

Tao Ren Semen persicae

According to a fifth aspect, the present invention provides a composition for therapeutic or prophylactic treatment of PMS, comprising the herbs:

Chai Hu Radix bupleuri

Bai Shao Radix paeoniae lactiflorae

Dang Gui Radix angelicae sinensis

Bai Zhu Rhizoma atractylodes Fu Ling Sclerotium poriae cocos Dan Shen Radix salviae miltiorrhizae Tao Ren Semen persicae He Huan Pi Cortex albizziae julibrissin and one or more, or all of: Xiang Fu Rhizoma cyperi rotundi Xu Duan Radix dipsacus

Preferably, the present invention also provides a composition according to any one of aspects 3 to 5, further including:

Chuan Niu Xi Radix cyathula

Yu Jin Radix curcumae

Chong Wei Zi Semen leonuri heterophylli

Chuan Xiong Radix ligustici wallichii Hong Hua Carthami flos

Chi Shao Radix paeoniae rubra

Ji Nei Jin Endothelium corneum gigeraiae galli

Xu Duan Radix dipsacus

Tu Si Zi Semen cuscatae Bu Gu Zhi Fructus psoraleae

Xiang Fu Rhizoma cyperi rotundi

Dang Shen Radix codonopsis pilulosae

Fu Shen Sclerotium poriae cocos

Chen Pi Pericarpium citri reticulate Gui Zhi Cinnamomum cassia

Qing Pi Pericarpium citri reticulatae viride

Suan Zao Ren Semen zizyphi spinosi

Mu Dan Pi Cortex moutan radicis

Yuan Zhi Radix polygalae Fu Shen Sclerotium poriae cocos

Huang Lian Rhizoma coptidis

Gou Teng Ramulus cum unicus uncariae

He Shou Wu Radix polygoni multiflorai

Shan Yu Rou Fructus corni officianalis Shan Yao Radix dioscorea Shu Di Radix rehmanniae Zhi Mu Radix anemarrhena Nu Zhen Zi Fructus ligustri lucidi Tu Si Zi Semen cuscatae Mai Ya Fructus hordei Jin Nei Jin Endothelium corneum gigeraiae galli Sheng Jiang Rhizoma zingiberis officinalis Bo He Herba menthae haplocalycis Gan Cao Glycyrrhiza uralensis Shi Chang Pu Rhizoma acori tatarinowa Pu Huang Typhae pollen Zhi Ke Fructus aurantii Mu Xiang Radix aucklandiae Wu Yao Radix linderae Lu Lu Tong Fructus liquidambaris Huang Qin Radix Scutellariae Shan Zha Fructus crataegi Zhi Gan Cao Radix glycyrrhiza uralensis Sheng Ma Rhizoma cimicifugae Wu Ling Zhi Tro gopter or i faeces Sha Ren Amomi fructus Gui Ban Testudinis plastrum Ji Xue Teng Caulis spatholobi Huang Qi Radix astragali

If required, Chai Hu and Xiang Fu could be replaced with Chuan Lian Zi {Fructus meliae toosendaή), and/or Bai Shao could be replaced with Chi Shao {Radix paeonia rubra), and/or Dang Gui could be replaced with He Shou Wu {Radix polygoni multiflorϊ) or Shu Di {Radix rehmanniae glutinosae conquitae), and/or Bai Zhu could be replaced with Dang Shen {Radix codonopsis pilulosae), and/or Fu Ling could be replaced with Yi Yi Ren {Semen coicis lachryma -jobϊ), and/or He Huan Pi could be replaced with He Huan Hua {Flos albizziae julibrissiή), and/or Xu Duan could be

replaced with Du Zhong (Cortex eucommiae), Ba Ji Tian (Radix morindae officinalis),

Chuan Niu Xi (Radix cyathulά) or Yin Yang Huo (Herba epimediϊ).

One or more herbs from additional subsets may be included in formulations of any one of the first to fifth aspects, if not already included, to enhance treatment of one or more symptoms associated with PMS. The preferred subsets are as follows:

Subset a: PMS associated with dysmenorrhoea, clotty menstrual flow or history of fibroids or endometriosis.

Tao Ren Semen persicae

Chuan Niu Xi Radix cyathula Yu Jin Radix curcumae

Chong Wei Zi Semen leonuri heterophylli

Chuan Xiong Radix ligustici wallichii

Hong Hua Carthami flos

Chi Shao Radix paeoniae rubra Pu Huang Typhae pollen

Wu Ling Zhi Trogopterori faeces

Subset b: PMS associated with marked lower back pain.

Xu Duan Radix dipsacus

Tu Si Zi Semen cuscatae Bu Gu Zhi Fructus psoraleae

Subset c: PMS associated with marked abdomen bloating and/or cramping.

Dang Shen Radix codonopsis pilulosae

Fu Shen Sclerotium poriae cocos

Chen Pi Pericarpium citri reticulate Gui Zhi Cinnamomum cassia

Qing Pi Pericarpium citri reticulatae viride

Zhi Ke Fructus aurantii

Mu Xiang Radix aucklandiae

Wu Yao Radix Under ae Subset d: PMS associated with marked irritability.

Suan Zao Ren Semen zizyphi spinosi

Mu Dan Pi Cortex moutan radicis

Subset e: PMS associated with insomnia, depression or poor concentration

Yuan Zhi Radix polygalae

Fu Shen Sclerotium poriae cocos

Huang Lian Rhizoma coptidis

Shi Chang Pu Rhizoma acori graminei Sheng Ma Rhizoma cimicifugae

Subset f: PMS associated with marked anger and/or headaches

Gou Teng Ramulus cum unicus uncariae

Subset g: PMS accompanied by excess blood loss and fatigue.

He Shou Wu Radix polygoni multiflorai Ji Xue Teng Caulis spatholobi

Huang Qi Radix astragali

Subset h: PMS associated with subfertility

Shan Yu Rou Fructus corni officianalis

Shan Yao Radix dioscorea Shu Di Radix rehmanniae

Zhi Mu Radix anemarrhena

Nu Zhen Zi Fructus ligustri lucidi

Tu Si Zi Semen cuscatae

Gui Ban Testudinis plastrum Subset i: PMS associated with constipation and/or digestive disorders.

Mai Ya Fructus hordei

Jin Nei Jin Endothelium corneum gigeraiae galli

Shan Zha Fructus crataegi

Huang Qin Radix Scutellaria Sha Ren Fructus amomi

Subset j: These herbs are added in small doses to increase efficacy of main formula and increase compliance through better digestibility and taste.

Sheng Jiang Rhizoma zingiberis officinalis

Bo He Herba menthae haplocalycis Gan Cao Radix glycyrrhiza uralensis

Zhi Gan Cao Radix glycyrrhiza uralensis (prepared differently)

Subset k: PMS associated with marked breast soreness and/or breast lumps.

Lu Lu Tong Fructus liquidambaris

According to a sixth aspect, the present invention provides a method of therapeutic or prophylactic treatment of PMS, comprising administering to a subject requiring such treatment, a composition of any one of the first to fifth aspects.

According to a seventh aspect, the present invention provides the use of a composition according to any one of the first to fifth aspects, in the manufacture of a medicament for the prophylactic or therapeutic treatment of PMS.

According to an eighth aspect, the present invention provides a composition according to any one of the first to fifth aspects, for use as a medicament.

It will be understood however, that the disorders and symptoms identified for treatment with formulations comprising the various subsets of herbs need not be as designated above. The designations are provided merely as an example of preferred groupings and possible indications of use.

In addition to effective treatment of PMS it will be understood from the disclosure provided herein that the formulations of the present invention may be suitably used, and be effective, in the treatment of symptoms and/or conditions accompanying and/or found associated with PMS. These are for example; a) dysmenorrhoea, clotty menstrual flow or history of fibroids or endometriosis, b) marked lower back pain, c) marked abdomen bloating and/or cramping, d) marked irritability, e) insomnia and poor concentration, f) marked anger and/or headaches, g) excess blood loss and fatigue, h) subfertility i) constipation and digestive disorders j) additional herbs e.g. better digestibility and taste k) marked breast soreness and/or breast lumps

Hence, when referring to formulations useful in the treatment of PMS, it is intended that such formulations are also useful in the treatment of PMS in combination with any one of the symptoms and/or conditions outlined above.

Formulations for treatment of the accompanying and/or associated symptoms and/or conditions will include, in addition to the core herb formulation, one or more herbs suitable for treatment of such symptoms.

The compositions can be formulated as dry powdered herbs and taken loose, or can be encapsulated or tabletted. The raw (un-powdered) herbs may also be provided that can be decocted for use by the patient. However, the compositions of the present invention can also be formulated with aqueous, organic or aqueous/organic extracts of the herbs, as would be understood by those skilled in the art, which extracts may be dried and formulated by conventional means. The composition may also be delivered in tablet or other solid dosage form, but it can also be delivered in a liquid or paste form. The composition may further include pharmaceutically acceptable excipients, adjuvants, solvents, disintegrators, carriers, flavours, colourings or coatings, and may be formulated in slow-release or controlled-release dosage formats.

Unless the context clearly requires otherwise, throughout the description and the claims, the words 'comprise', 'comprising', and the like are to be construed in an inclusive sense as opposed to an exclusive or exhaustive sense; that is to say, in the sense of "including, but not limited to". DESCRIPTION OF THE PREFERRED EMBODIMENT

The treatment of medical disorders using herbal formulations differs from orthodox Western-style treatments in that the herbal formulations are intended to be tailored to meet the specific requirements of each patient. The present invention provides base or core formulations that are effective in the treatment of PMS. Also provided are expanded formulations which include the core formulations and additional herbs for effective treatment or alleviation of associated symptoms that may manifest in a patient diagnosed with PMS.

Moreover, the formulations of the present invention are more efficacious and have less side-effects than medications and formulations previously or currently available.

The components of a preferred formulation effective in the treatment of PMS, comprises the herbs:

Chai Hu Radix bupleuri

Bai Shao Radix paeoniae lactiflorae Dang Gui Radix angelicae sinensis

Bai Zhu Rhizoma atractylodes

Fu Ling Sclerotium poriae cocos

Dan Shen Radix salviae miltiorrhizae

He Huan Pi Cortex albizziae julibrissin

Xiang Fu Rhizoma cyperi rotundi

Xu Duan Radix dipsacus

The components of another preferred formulation effective in the treatment of PMS, comprises the herbs:

Chai Hu Radix bupleuri

Bai Shao Radix paeoniae lactiflorae

Dang Gui Radix angelicae sinensis

Bai Zhu Rhizoma atractylodes

Fu Ling Sclerotium poriae cocos

Dan Shen Radix salviae miltiorrhizae

He Huan Pi Cortex albizziae julibrissin

Xiang Fu Rhizoma cyperi rotundi

Xu Duan Radix dipsacus and one or more, or all of:

Tao Ren Semen per sicae

Chuan Niu Xi Radix cyathula

Yu Jin Radix curcumae

Chong Wei Zi Semen leonuri heterophylli

Chuan Xiong Radix ligustici wallichii

Hong Hua Carthami flos

Chi Shao Radix paeoniae rubra

Ji Nei Jin Endothelium corneum gigeraiae galli

Xu Duan Radix dipsacus

Tu Si Zi Semen cuscatae

Bu Gu Zhi Fructus psoraleae

Xiang Fu Rhizoma cyperi

Dang Shen Radix codonopsis pilulosae

Fu Shen Sclerotium poriae cocos

Chen Pi Pericarpium citri reticulate

Gui Zhi Cinnamomum cassia

Qing Pi Pericarpium citri reticulatae viride

Suan Zao Ren Semen zizyphi spinosi

Mu Dan Pi Cortex moutan radicis

Yuan Zhi Radix polygalae Fu Shen Sclerotium poriae cocos Huang Lian Rhizoma coptidis Gou Teng Ramulus cum unicus uncariae He Shou Wu Radix polygoni multiflorai Shan Yu Rou Fructus corni officianalis Shan Yao Radix dioscorea Shu Di Radix rehmanniae Zhi Mu Radix anemarrhena Nu Zhen Zi Fructus ligustri lucidi Tu Si Zi Semen cuscatae Mai Ya Fructus hordei Sheng Jiang Rhizoma zingiberis officinalis Bo He Herba menthae haplocalycis Gan Cao Glycyrrhiza uralensis

Shi Chang Pu Rhizoma acori tatarinowa Pu Huang Typhae pollen Zhi Ke Fructus aurantii Mu Xiang Radix aucklandiae Wu Yao Radix linderae Lu Lu Tong Fructus liquidambaris Huang Qin Radix scuttellariae Shan Zha Fructus crataegi Zhi Gan Cao Radix glycyrrhiza uralensis Sheng Ma Rhizoma cimicifugae Wu Ling Zhi Trogopterori faeces Sha Ren Amomi fructus Gui Ban Testudinis plastrum Ji Xue Teng Caulis spatholobi Huang Qi Radix astragali

The components of another preferred formulation effective in the treatment of PMS, comprises the herbs: Chai Hu Radix bupleuri

Bai Shao Radix paeoniae lactiβorae

Dang Gui Radix angelicae sinensis and one or more, or all of: Bai Zhu Rhizoma atractylodes Fu Ling Sclerotium poriae cocos Dan Shen Radix salviae miltiorrhizae He Huan Pi Cortex albizziae julibrissin Xiang Fu Rhizoma cyperi rotundi Xu Duan Radix dipsacus Tao Ren Semen per sicae The components of another preferred formulation effective in the treatment of

PMS, comprises the herbs: Chai Hu Radix bupleuri

Bai Shao Radix paeoniae lactiflorae Dang Gui Radix angelicae sinensis Bai Zhu Rhizoma atractylodes Fu Ling Sclerotium poriae cocos Dan Shen Radix salviae miltiorrhizae and one or more, or all of: He Huan Pi Cortex albizziae julibrissin Xiang Fu Rhizoma cyperi rotundi Xu Duan Radix dipsacus Tao Ren Semen per sicae

The components of another preferred formulation effective in the treatment of PMS, comprises the herbs: Chai Hu Radix bupleuri

Bai Shao Radix paeoniae lactiflorae

Dang Gui Radix angelicae sinensis

Bai Zhu Rhizoma atractylodes

Fu Ling Sclerotium poriae cocos Dan Shen Radix salviae miltiorrhizae

Tao Ren Semen per sicae

He Huan Pi Cortex albizziae julibrissin and one or more, or all of:

Xiang Fu Rhizoma cyperi rotundi

Xu Duan Radix dipsacus

Preferably the above formulations also comprise one or more, or all of the following herbs:

Chuan Niu Xi Radix cyathula Yu Jin Radix curcumae

Chong Wei Zi Semen leonuri heterophylli

Chuan Xiong Radix ligustici wallichii

Hong Hua Carthami flos

Chi Shao Radix paeoniae rubra Ji Nei Jin Endothelium corneum gigeraiae galli

Xu Duan Radix dipsacus

Tu Si Zi Semen cuscatae

Bu Gu Zhi Fructus psoraleae

Xiang Fu Rhizoma cyperi rotundi Dang Shen Radix codonopsis pilulosae

Fu Shen Sclerotium poriae cocos

Chen Pi Pericarpium citri reticulate

Gui Zhi Cinnamomum cassia

Qing Pi Pericarpium citri reticulatae viride Suan Zao Ren Semen zizyphi spinosi

Mu Dan Pi Cortex moutan radicis

Yuan Zhi Radix polygalae

Fu Shen Sclerotium poriae cocos

Huang Lian Rhizoma coptidis Gou Teng Ramulus cum unicus uncariae

He Shou Wu Radix polygoni multiβorai

Shan Yu Rou Fructus corni officianalis

Shan Yao Radix dioscorea

Shu Di Radix rehmanniae Zhi Mu Radix anemarrhena

Nu Zhen Zi Fructus ligustri lucidi

Tu Si Zi Semen cuscatae

Mai Ya Fructus hordei

Jin Nei Jin Endothelium corneum gigeraiae galli

Sheng Jiang Rhizoma zingiberis officinalis

Bo He Herba menthae haplocalycis

Gan Cao Glycyrrhiza uralensis

Shi Chang Pu Rhizoma acori tatarinowa Pu Huang Typhae pollen

Zhi Ke Fructus aurantii

Mu Xiang Radix aucklandiae

Wu Yao Radix linderae

Lu Lu Tong Fructus liquidambaris Huang Qin Radix scuttellariae

Shan Zha Fructus crataegi

Zhi Gan Cao Radix glycyrrhiza uralensis

Sheng Ma Rhizoma cimicifugae

Wu Ling Zhi Trogopterori faeces Sha Ren Amomi fructus

Gui Ban Testudinis plastrum

Ji Xue Teng Caulis spatholobi

Huang Qi Radix astragali

The formulations of the present invention are primarily intended to be generic formulations that can be used without major changes for all female patients with PMS, the only changes to the formulation being those that allow treatment of certain symptoms and/or conditions accompanying and/or associated with PMS in addition to

PMS itself. However, specific tailored formulations comprising the core and additional supplementary herbs, which may usefully be prescribed for treatment, are also included as individual embodiments of the present invention.

One or more herbs from additional subsets may be included in formulations that do not already include them, to enhance treatment of symptoms associated with

PMS. Such subsets may be chosen from:

Subset a: PMS associated with dysmenorrhoea, clotty menstrual flow or history of fibroids or endometriosis.

Tao Ren Semen persicae

Chuan Niu Xi Radix cyathula

Yu Jin Radix curcumae

Chong Wei Zi Semen leonuri heterophylli

Chuan Xiong Radix ligustici wallichii

Hong Hua Carthamiflos

Chi Shao Radix paeoniae rubra

Pu Huang Typhae pollen Wu Ling Zhi Trogopterori faeces

Subset b: PMS associated with marked lower back pain.

Xu Duan Radix dipsacus

Tu Si Zi Semen cuscatae

Bu Gu Zhi Fructus psoraleae Subset c: PMS associated with marked abdomen bloating and/or cramping.

Dang Shen Radix codonopsis pilulosae

Fu Shen Sclerotium poriae cocos

Chen Pi Pericarpium citri reticulate

Gui Zhi Cinnamomum cassia Qing Pi Pericarpium citri reticulatae viride

Zhi Ke Fructus aurantii

Mu Xiang Radix aucklandiae

Wu Yao Radix linderae

Subset d: PMS associated with marked irritability. Suan Zao Ren Semen zizyphi spinosi

Mu Dan Pi Cortex moutan radicis

Subset e: PMS associated with insomnia, depression or poor concentration

Yuan Zhi Radix polygalae

Fu Shen Sclerotium poriae cocos Huang Lian Rhizoma coptidis

Shi Chang Pu Rhizoma acori graminei

Sheng Ma Rhizoma cimicifugae

Subset f: PMS associated with marked anger and/or headaches

Gou Teng Ramulus cum unicus uncariae Subset g: PMS accompanied by excess blood loss and fatigue.

He Shou Wu Radix polygoni multiflorai

Ji Xue Teng Caulis spatholobi

Huang Qi Radix astragali

Subset h: PMS associated with subfertility

Shan Yu Rou Fructus corni officianalis

Shan Yao Radix dioscorea

Shu Di Radix rehmanniae

Zhi Mu Radix anemarrhena Nu Zhen Zi Fructus ligustri lucidi

Tu Si Zi Semen cuscatae

Gui Ban Testudinis plastrum

Subset i: PMS associated with constipation and/or digestive disorders.

Mai Ya Fructus hordei Jin Nei Jin Endothelium corneum gigeraiae galli

Shan Zha Fructus crataegi

Huang Qin Radix Scutellaria

Sha Ren Fructus amomi

Subset j: These herbs are added in small doses to increase efficacy of main formula and increase compliance through better digestibility and taste

Sheng Jiang Rhizoma zingiberis officinalis

Bo He Herba menthae haplocalycis

Gan Cao Radix glycyrrhiza uralensis

Zhi Gan Cao Radix glycyrrhiza uralensis (prepared differently) Subset k: PMS associated with marked breast soreness and/or breast lumps.

Lu Lu Tong Fructus liquidambaris

The present invention also provides a composition, wherein the composition treats or alleviates a symptom and/or condition accompanying and/or associated with

PMS. The herbal formulation of the present invention can be administered orally or parenterally in any conventional form such as example granules, capsules, tablets, elixirs, powders, granules, suspensions in water or non-aqueous media, and sachets as additives to food or beverages.

The herbal formulation may be produced utilizing concentrated herbal extract, either an extract of the total formulation, or by combining separate extracts of individual herbs. Such extracts may be employed as the base materials in the manufacture of tablets or powders. Methods for preparing herbal formulations using herbal extracts are well known and are described in numerous texts and manuals, for example Bensky, D. and Barolet, R. "Chinese Herbal Medicine Formulas and

Strategies", 1990 Eastland Press (pgs 18 - 24) and Bensky, D., Clavey, S. and Stoger E., Chinese Herbal Medicine", Materia Medica, 3 ^rd Ed. 2004 and the like, incorporated in their entirety herein by reference.

In powder form, the various dry powdered ingredients are mixed together until a substantially homogeneous mixture is obtained. The powder can be administered by mixing with a liquid, such as water or juice for consumption of the resulting suspension. Liquid preparations may take the form of, for example, solutions, syrups or suspensions or they may be presented as a dry powder for reconstitution with an appropriate liquid carrier, preferably water, for oral administration or for packaging in containers for example in ampoules or in multi-dose containers. Such liquid preparations may be prepared by conventional means with pharmaceutically acceptable additives such as suspending agents, emulsifying agents, preservatives, non-aqueous vehicles example almond oil, oily esters or ethyl alcohol and artificial or natural colours and/or sweeteners. The composition may also be delivered in a capsule or tablet dosage form, but it can also be delivered in a liquid or paste form. In tablet form, the ingredients are mixed together and the tablets prepared according to methods well known in the art, for example the wet granulation method, the dry- granulation method or direct compression. The composition may further include pharmaceutically acceptable excipients, adjuvants, solvents, disintegrators, carriers, flavours, colourings or coatings. The tablets may be uncoated, or may be coated by known techniques to delay disintegration and absorption in the gastrointestinal tract and thereby provide a sustained action over a longer period. For methods of preparing various types of formulations and choice of carriers, excipients and additives, see standard pharmacy texts and manuals such as for example Remington: The Science and Practice of Pharmacy, 19 ^th Ed., Mack Publishing Co., 1995, the Theory and Practice of Industrial Pharmacy, Lachman L., et al. Lea & Febiger, Philadelphia 3 ^rd Edition, Bentley's Textbook of Pharmaceutics Ed. EA Rawlings Ballilliere Tindall, London 8 ^th Edition incorporated in its entirety herein by reference.

Animals or humans may be treated in accordance with the invention. The herbal formulations are preferably administered orally and in dosage units. For treatment of a subject, depending on activity of the herbal formulation, manner of administration, nature and severity of the disorder, age and body weight of the subject, different daily doses can be used. Under certain circumstances, however, higher or lower doses may be appropriate. The administration of the daily dose can be carried

out both by single administration in the form of an individual dose unit or else several smaller dose units and also by multiple administration of subdivided doses at specific intervals. It will be appreciated that the formulation may also be administered via a slow release device. The present invention also provides a method of therapeutic or prophylactic treatment of PMS, comprising administering to a subject requiring such treatment, a composition according to the invention.

The present invention also provides use of composition according to the invention, in the manufacture of a medicament for the prophylactic or therapeutic treatment of PMS.

The present invention is also directed to methods of treating or alleviating the symptoms and/or conditions accompanying and/or associated with PMS, for example, dysmenorrhoea, clotty menstrual flow or history of fibroids or endometriosis, marked lower back pain, marked abdomen bloating and/or cramping, marked irritability, insomnia, depression and poor concentration, marked anger and/or headaches, excess blood loss and fatigue, subfertility and/or constipation and marked breast soreness and/or lumps.

The present invention is also directed to the use of the composition as a medicament. A preferred dose for treating or preventing PMS and associated symptoms is in the range of 3g - 15g (equivalent raw herb dosage) per day in a single dose or multiple doses. More preferably it is 3g-5g (equivalent raw herb dosage) once or twice per day. However, the exact dose depends to a great extent on the severity of PMS, the general health of the patient and the presence of any accompanying symptoms. The required dosage can be easily established by a practitioner skilled in the art.

Generally, the terms "treating", "treatment" and the like are used herein to mean affecting a subject, tissue or cell to obtain a desired pharmacological and/or physiological effect. The effect may be prophylactic in terms of completely or partially preventing PMS or accompanying symptoms and/or associated conditions, and/or may be therapeutic in terms of a partial or complete cure of a disorder. "Treating" as used herein covers any therapy of, or prevention of, PMS in a mammal, particularly a human, and includes preventing the disorder from occurring in a subject who may be predisposed to the disorder, but has not yet been diagnosed as having it;

inhibiting the disorder, Le. arresting its development; or relieving or ameliorating the effects of the disorder i.e. cause regression of the effects of the disorder.

Preferred embodiments of the invention will now be described by way of example only with reference to the following case studies. The examples demonstrate the use of preferred formulations of the present invention in the treatment of PMS in association with a number of symptoms and/or conditions.

EXAMPLES Example 1 : Formulations and Preparation

. For the purpose of conducting clinical studies, all herbs were used in the dried powdered form. If desired the herbs may be encapsulated before administration. If sufficiently dry, the herbs were powdered using a grinder or similar device. If the moisture content of the herbs was high, the herbs were baked before being powdered.

Although fresh or dried herbs can be used, the herbs may also be formulated by one of the following methods: (a) concentrating either a water or an organic solvent (e.g. alcohol) extract of each herb and then combining the extracts;

(b) all the raw herbs can be boiled together and then concentrated by spray drying or other known methods into a dry granulated formulation. The extracts can be concentrated before or after combining and may be processed into tablets or capsules.

Methods for preparing herbal formulations are well known and are the subject of numerous texts and manuals, for example "Chinese Herbal Medicine", Materia Medica, 3 ^rd Ed. 2004 and the like, incorporated in its entirety herein by reference.

As a specific example, when using granules the formula is constructed typically with 3 - 15 g of each herb. A typical dose in the range of 3-5 g (about a teaspoon) of the formula is then taken twice a day in form of a tea. When using raw herbs for decoction the formula makes use of approximately the same amount of each herb (ie. typically 3-15 g) and the entire formula is then boiled together in 2-3 cups of water until it is reduced to an amount of about one cup (approximately 45 minutes but the time can range from about 20 to about 60 minutes). This is then drunk at once or in divided doses over the course of the day. In some instances the same herbs can be decocted a second time the following day with the addition of 2 cups of water and boiled down to about one cup. This cup can be drunk at once or in divided doses over the course of the day. These herbs are then discarded.

The components of a preferred formulation of the present invention are listed in Table 1 below.

Chinese name Pharmaceutical name Amount (grri)

Chai Hu Radix bupleuri 12 Bai Shao Radix paeoniae lactiflorae 12

Dang Gui Radix angelicae sinensis 9

Bai Zhu Rhizoma atractylodes 9

Fu Ling Sclerotium poriae cocos 15

Dan Shen Radix salviae miltiorrhizae 9 He Huan Pi Cortex albizziae julibrissin 9

Xiang Fu Rhizoma cyperi rotundi 9

Xu Duan Radix dipsacus 9

Certain additional herbs may be used in conjunction with the above formulations, to create further formulations, depending on which accompanying symptom or associated conditions need treatment. One or more such additional herbs can be chosen from the following subsets:

Subset a: PMS associated with dysmenorrhoea, clotty menstrual flow or history of fibroids or endometriosis.

Tao Ren Semen persicae Chuan Niu Xi Radix cyathula

Yu Jin Radix curcumae

Chong Wei Zi Semen leonuri heterophylli

Chuan Xiong Radix ligustici wallichii

Hong Hua Carthami flos Chi Shao Radix paeoniae rubra

Pu Huang Typhae pollen

Wu Ling Zhi Trogopterori faeces

Subset b: PMS associated with marked lower back pain.

Xu Duan Radix dipsacus Tu Si Zi Semen cuscatae

Bu Gu Zhi Fructus psoraleae

Subset c: PMS associated with marked abdomen bloating and/or cramping.

Dang Shen Radix codonopsis pilulosae

Fu Shen Sclerotium poriae cocos

Chen Pi Pericarpium citri reticulate

Gui Zhi Cinnamomum cassia

Qing Pi Pericarpium citri reticulatae viride

Zhi Ke Fructus aurantii Mu Xiang Radix aucklandiae

Wu Yao Radix linderae

Subset d: PMS associated with marked irritability.

Suan Zao Ren Semen zizyphi spinosi

Mu Dan Pi Cortex moutan radicis Subset e: PMS associated with insomnia, depression or poor concentration

Yuan Zhi Radix polygalae

Fu Shen Sclerotium poriae cocos

Huang Lian Rhizoma coptidis

Shi Chang Pu Rhizoma acori graminei Sheng Ma Rhizoma cimicifugae

Subset f: PMS associated with marked anger and/or headaches

Gou Teng Ramulus cum unicus uncariae

Subset g: PMS accompanied by excess blood loss and fatigue.

He Shou Wu Radix polygoni multiβorai Ji Xue Teng Caulis spatholobi

Huang Qi Radix astragali

Subset h: PMS associated with subfertility

Shan Yu Rou Fructus corni officianalis

Shan Yao Radix dioscorea Shu Di Radix rehmanniae

Zhi Mu Radix anemarrhena

Nu Zhen Zi Fructus ligustri lucidi

Tu Si Zi Semen cuscatae

Gui Ban Testudinis plastrum Subset i: PMS associated with constipation and/or digestive disorders.

Mai Ya Fructus hordei

Jin Nei Jin Endothelium corneum gigeraiae galli

Shan Zha Fructus crataegi

Huang Qin Radix Scutellaria

Sha Ren Fructus amomi

Subset j: These herbs are added in small doses to increase efficacy of main formula and increase compliance through better digestibility and taste. Sheng Jiang Rhizoma zingiberis officinalis Bo He Herba menthae haplocalycis

Gan Cao Radix glycyrrhiza uralensis

Zhi Gan Cao Radix glycyrrhiza uralensis (prepared differently)

Subset k: PMS associated with marked breast soreness and/or breast lumps.

Lu Lu Tong Fructus liquidambaris The herbs described below in the case studies were taken in the two weeks before the period, i.e. before and during the time of PMS. The improvements in symptoms described by the patients refer to the menstrual cycle during which the herbs were actually taken. Dose was 3g-5g of granules twice a day.

The formulations used in the following case studies lead in part to the development of the generic formulations of the present invention. Example 2: Case Study 1

The patient presented with PMS; symptoms included bloating, abdominal cramping, lower back pain, irritability, insomnia and poor concentration.

After she took the following herbs she reported that her all her premenstrual symptoms were overall much improved.

Chinese name Pharmaceutical name Amount (grn)

Chai Hu Radix bupleuri 15

Bai Shao Radix paeoniae lactiflorae 15

Fu Ling Sclerotium poriae cocos 15 Bai Zhu Rhizoma atractylodes 15

Dang Gui Radix angelicae sinensis 15

Dan Shen Radix salviae miltiorrhizae 6 and

Sheng Jiang Rhizoma zingiberis officinalis 6 Bo He Herba menthae haplocalucis 6

Gan Cao Radix glycyrrhiza uralensis 6

Wu Ling Zhi Trogopterori faeces 6

Tao Ren Semen per sicae 6

At a later visit she took the following formula and reported that in addition to the previous months improvements, there was no longer any back pain at all before her period. Chinese name Pharmaceutical name Amount (gm)

Dang Gui Radix angelicae sinensis 9

Bai Zhu Rhizoma atractylodes 9

He Huan Pi Cortex albizziae julibrissin 9

Dan Shen Radix salviae miltiorrhizae 9 and

Fu Shen Sclerotium poriae cocos 6

Tu Si Zi Semen cuscatoe 9

Bu Gu Zhi Fructus psoraleae 9

Dang Shen Radix codonopsis pilulosae 9 Yuan Zhi Radix plygalae 9

Huang Lian Rhizoma coptidis 5

He Shou Wu Radix polygoni multiflora 9

Example 3: Case Study 2

The patient presented with PMS; symptoms included fatigue, constipation, depression, anxiety, occasional sore breasts and irritability.

After taking the following herbs she reported that all her premenstrual symptoms were all markedly reduced. Chinese name Pharmaceutical name Amount (gm)

Chai Hu Radix bupleuri 12 Bai Zhu Rhizoma atractylodes 9

Fu Ling Sclerotium poriae cocos 10

Dang Gui Radix angelicae sinensis 10

Bai Shao Radix paeoniae lactiflorae 15

He Huan Pi Cortex albizziae julibrissin 10 and

Shan Yu Rou Fructus corni officianolis 12

Shan Yao Radix dioscorea 10

Shu Di Radix rehmanniae 10

Dan Pi Cortex moutan radicis 10

Zhi Mu Radix anemarrhena 6

He Shou Wu Radix polygoni multifloro 10

Mai Ya Fructus hordei 10

Ji Nei Jin Endothelium corneum gigeraiae galli 6 Sha Ren Fructus amomi 3

Example 4: Case Study 3

The patient presented with PMS; symptoms included mood swings, irritability, bloating and lethargy.

After taking the following herbs she reported that her moods were much improved.

Chinese name Pharmaceutical name Amount (gm)

Chai Hu Radix bupleuri 10

Bai Shao Radix paeoniae lactiflorae 9

Bai Zhu Rhizoma atractylodes 9 Fu Ling Sclerotium poriae cocos 9

Dan Shen Radix salviae miltiorrhizae 9

Dang Gui Radix angelicae sinensis 9 and

Sheng Jiang Rhizoma zingiberis officinalis 6 Bo He Herba menthae haplocalycis 6

Gan Cao Glycyrrhiza uralensis 3

Dan Pi Cortex moutan radicis 9

Fu Shen Sclerotium poriae cocos 9

Example 5: Case Studv 4 The patient presented with PMS; symptoms included abdomen pain, spotting of blood, tender breasts and anxiety.

After taking the following herbs she had no premenstrual symptoms at all. Chai Hu Radix bupleuri 9

Bai Shao Radix paeoniae lactiflorae 9 Dang Gui Radix angelicae sinensis 9

Bai Zhu Rhizoma atractylodes 9

Fu Ling Sclerotium poriae cocos 9

He Huan Pi Cortex albizziae julibrissin 9 and

Sheng Jiang Rhizoma zingiberis officinalis 3

Bo He Herba menthae haplocalycis 3

Gan Cao Radix glycyrrhiza uralensis 3

Gui Ban, Testudinis plastrum 9 Shu Di, Radix rehmanniae 6

Chuan NIu Xi Radix cyathulae 6

Example 6: Case Study 5

The patient presented with PMS; symptoms included bloating, sore breasts and was emotional. She experienced none of these signs and symptoms of PMS after taking the herbs below. Chinese name Pharmaceutical name Amount (em)

Chai Hu Radix bupleuή 9

Bai Shao Radix paeoniae lactiflorae 9 Dang Gui Radix angelicae sinensis 9

Bai Zhu Rhizoma atractylodes 9

Fu Ling Sclerotium poriae cocos 9

Dan Shen Radix salviae miltiorrhizae 9 and He Shou Wu Radix polygoni multiflora 9

Chen Pi Pericarpium citri reticulate 6

Gui Zhi Cinnamomum cassia 6

Nu Zhen Zi Fructus ligustri lucidi 6

Tu Si Zi Semen cuscatae 9 Chuan Xiong Radix ligustici wallichii 6

Example 7: Case Studv 6

The patient presented with PMS; symptoms included intolerance and extreme emotions like anger, and she was very easily upset.

After taking these herbs she said she coped much better before her period and was not angry.

Chinese name Pharmaceutical name Amount (em)

Chai Hu Radix bupleuri 12

Bai Shao Radix paeoniae lactiflorae 15

Dang Shen Radix codonopsis pilulosae 9

Dan Shen Radix salviae miltiorrhizae 9

Fu Ling Sclerotium poriae cocos 12

Dang Gui Radix angelicae sinensis 9

He Huan Pi Cortex albizziae julibrissin 9 and

Tao Ren Semen persicae 5

Example 8: Case Study 7

The patient presented with PMS; symptoms included anger, irritability, and swollen breasts. The above symptoms of PMS disappeared when she took these herbs: Chinese name Pharmaceutical name Amount ( gm)

Chai Hu Radix bupleuri 12

Fu Ling Sclerotium poriae cocos 10

Bai Shao Radix paeoniae lactiflorae 10 Dang Gui Radix angelicae sinensis 10

Dan Shen Radix salviae miltiorrhizae 15

He Huan Pi Cortex albizziae julibrissin 9 and

Suan Zao Ren Semen zizyphi spinosi 18 Gou Teng Ramulus cum unicus uncariae 12

Tao Ren Semen persicae 9

Yu Jin Radix curcumae 9

Chong Wei Zi Semen leonuri heterophylli 6

Example 9: Case Study 8 The patient presented with PMS; symptoms included irritability, anger, sore breasts, headaches, abdominal bloating and cramping.

In the month she took these herbs her breast soreness was reduced to 1 day and all the other symptoms were resolved.

Chinese name Pharmaceutical name Amount (gm) Chai Hu Radix bupleuri 6

Bai Shao Radix paeoniae lactiflorae 12

Dang Gui Radix angelicae sinensis 12

Dan Shen Radix salviae miltiorrhizae 10

Xiang Fu Rhizoma cyperi rotundi 10

Xu Duan Radix dipsacus 12 and Ji Xue Teng Caulis spatholobi 12

Chi Shao Radix paeonia rubra 10

Tao Ren Semen persicae 5

Chuan Xiong Radix ligustici wallichii 5

Hong Hua Carthami flos 3 Qing Pi Pericarpium citri reticulatae viride 6

Huang Qi Radix astragali 12

Example 10: Case Study 11

The patient presented with PMS since puberty, and recently it was getting worse. For 7 to 10 days every month she became irritable, tense, depressed and teary.

Her breasts were very tender, her abdomen bloated and she had diarrhoea. She was fatigued, forgetilil and suffered dull headaches. Her lower back became painful.

Chinese name Pharmaceutical name Amount fgm) Chai Hu Radix bupleuri 10

Bai Shao Radix paeoniae lactiflorae 10

Bai Zhu Rhizoma atractylodes 10

Dang Gui Radix angelicae sinensis 10

He Huan Pi Cortex albizziae julibrissin 15 Xu Duan Radix dipsacus 10 and

Huang Qi Radix astragali 15

Shi Chang Pu Rhizoma acori graminei 12

Pu Huang Typhae pollen 10 Wu Ling Zhi Trogopterori faeces 10

Yuan Zhi Radix polygalae 10

After 2 weeks of taking these she reported that before her period she was less irritable, less bloated. There was no breast soreness at all and no diarrhoea. The lower back pain and the headache was still present.

She was recommended to continue the herbs. Example 11: Case Study 12

Since she was a teenager, the patient experienced breast tenderness, depression and tearyness, abdomen bloating, indigestion with marked burping, fatigue and lower back pain in the two weeks before her menstrual periods.

She was prescribed: Cycle 1 Chinese name Pharmaceutical name Amount (gm)

Chai Hu Radix bupleuri 10 Bai Shao Radix paeoniae lactiflorae 10

Dang Gui Radix angelicae sinensis 10

Dan Shen Radix salviae miltiorrhizae 10

He Huan Pi Cortex albizziae julibrissin 12

Xiang Fu Rhizoma cyperi rotundi 12 and

Fu Shen Sclerotium poriae cocos 6

Yi Yi Ren Semen coicis lachryma —jobi 10

Zhi Ke Fructus aurantii 6

Mu Xiang Radix aucklandiae 6 Shi Chang Pu Rhizoma acori graminei 6 and

Wu Yao Radix linderae 6

Chuan Xiong Radix ligustici wallichii 6

PMS improved markedly in all respects except the breast tenderness which persisted, as did the burping.

Cycle 2 - repeat the same herbs (as above) with the addition of

Chinese name Pharmaceutical name Amount (gm)

Chuan Lian Zi Fructus meliae toosendan 6

Lu Lu To ng Fructus liquidambaris 10 PMS same i.e. improvement of all symptoms except breasts still tender and burping still bothered her. Cycle 3 Chinese name Pharmaceutical name Amount (gm)

Chai Hu Radix bupleuri

Bai Shao Radix paeoniae lactiflorae 15 Xiang Fu Rhizoma cyperi rotundi 9 He Huan Pi Cortex albizziae julibrissin 15 and Zhi Ke Aurantii fructus 9 Chuan Xiong Radix ligustici wallichii 6 Chen Pi Pericarpium citri reticulate 9 Huang Qin radix Scutellaria 12 Shi Chang Pu Rhizoma acori graminei 9 Shan Zha Fructus crataegi 6 Zhi Gan Cao Radix glycyrrhiza uralensis 3

PMS symptoms resolved including breast tenderness, which was now much reduced.

Burping persisting.

Cycle 4

Chinese name Pharmaceutical name Amount (grn)

Chai Hu Radix bupleuri 9 Bai Shao Radix paeoniae lactiflorae 9 Dang Gui Radix angelicae sinensis 9 Bai Zhu Rhizoma atractylodes 9 Fu Ling Sclerotium poriae cocos 9 Xiang Fu Rhizoma cyperi rotundi 6 and

Bu Gu Zhi Fructus psoraleae 9 Chuan Xiong Radix ligustici wallichii 9 Ji Xue Teng Caulis spatholobi 12 Sheng Ma Rhizoma cimicifugae 6 Chen Pi Pericarpium citri reticulate 6 Sheng Jiang Rhizoma zingiberis officinalis 3 Bo He Herba menthae haplocalycis 3 Gan Cao Radix glycyrrhiza uralensis 3

PMS - The patient now has no breast tenderness at all, i.e. PMS resolved except for burping.

Treatment for PMS was discontinued at this point, and treatment which focussed soley on digestion was instituted.

Although the present invention has been described with reference to certain preferred embodiments and examples, it will be understood that variations in keeping with the spirit and thrust of the invention described are also within its scope.