Herbal compositions and methods for treating menorrhagia

TECHNICAL FIELD

This invention relates to new medicinal compositions and methods for treating menorrhagia 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.

Menorrhagia is defined as excessive blood loss associated with menstruation. There may be deluge bleeding during the normal course of the period or there may be an extended time (up to ten days) of menstrual bleeding or both. The cause of the heavy bleeding may be fibroids in the uterine cavity but often it is related to hormone imbalance, causing the uterine lining to thicken excessively. Continued menorrhagia leads to anaemia and debility. In young women it is sometimes treated with NSAID's used to treat period pain, but with limited effectiveness. Alternatively an implant such as an intrauterine device (IUD) impregnated with hormones may be required. In women past child bearing age, the treatment is surgical - either removal of fibroids, removal of the uterine lining or most commonly removal of the uterus itself.

In all cases except where fibroids are very large, this condition can be treated effectively by certain herbal remedies, however efficacy is variable and treatment is not standardised. There are few if any reported clinically trials of such remedies.

Therefore there is a need for novel therapies for the treatment of menorrhagia, 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 an effective treatment for menorrhagia in western women, without the risks inherent in the drug or surgical treatment options. The formulations provide an effective treatment by regulating hormones, reducing the thickness of the uterine lining and controlling the amount of blood lost, and by improving or alleviating one or more other symptoms accompanying or associated with menorrhagia, such as anaemia like pallor and fatigue.

Accordingly, in a first aspect, the present invention provides a composition for prophylactic or therapeutic treatment of menorrhagia, comprising the herbs: Huang Qi Radix astragali

Yi Mu Cao Herba leonuri heterophylli Sheng Di Radix rehmanniae

San Qi Radix pseudoginseng

He Shou Wu Radix polygoni multiflori

Pu Huang Pollen typhae

If required Huang Qi could be replaced with Dang Shen, and/or Sheng Di could be replaced with Shu Di or Xuan Shen {Radix scrophulariae), and/or He Shou Wu could be replaced with Dang Gui or Shu Di, and/or Yi Mu Cao could be replaced with Yan Hu Suo, and/or Pu Huang could be replaced with Dan Shen.

According to a second aspect, the present invention provides a method of therapeutic or prophylactic treatment of menorrhagia, comprising administering to a subject requiring such treatment, a composition of the first aspect.

According to a third aspect, the present invention provides the use of a composition according to the first aspect, in the manufacture of a medicament for the prophylactic or therapeutic treatment of menorrhagia.

According to a fourth aspect, the present invention provides use of a composition according to the first aspect, as a medicament.

Preferably, a composition according to the invention treats or alleviates a symptom and/or condition accompanying or associated with menorrhagia.

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.

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 and 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 dosage 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 menorrhagia. 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 prophylactic or therapeutic treatment of menorrhagia, comprise the herbs: Huang Qi Radix astragali

Yi mu Cao Herba leonuri heterophylli

Sheng Di Radix rehmanniae

San Qi Radix pseudoginseng He Shou Wu Radix polygoni multiflori

Pu Huang Pollen typhae

Certain herbs in the above composition may be replaced with other herbs that have a similar activity or function, should this be required for any reason. Thus, Huang Qi could be replaced with Dang Shen, and/or Sheng Di could be replaced with Shu Di or Xuan Shen {Radix scrophulariae), and/or He Shou Wu could be replaced with Dang Gui or Shu Di, and/or Yi Mu Cao could be replaced with Yan Hu Suo .and/or and Pu Huang could be replaced with Dan Shen.

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 menorrhagia. Preferably, a composition according to the invention treats or alleviates a symptom and/or condition accompanying or associated with menorrhagia.

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 extracts, 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 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 is also directed to methods of therapeutic or prophylactic treatment of menorrhagia, comprising administering to a subject requiring such treatment, a composition according to the invention.

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

The present invention is also directed to methods of treating or alleviating the symptoms and/or conditions accompanying or associated with menorrhagia, for example anaemia like pallor and fatigue.

The present invention is also directed to use of the composition as a medicament.

A preferred dose for treating or preventing menorrhagia and associated symptoms is in the range of 3g-15g (equivalent raw herb dosage) per day in a single does 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 menorrhagia, the general health of the patient and the presence of any accompanying symptoms. The required dosage can be easily established by practitioners 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 menorrhagia, 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, menorrhagia 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, i.e. arresting its development.

Preferred embodiments of the invention will now be described by way of example only with reference to the following case studies. Examples demonstrate the use of preferred formulation of the present invention in the treatment of menorrhagia.

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 (i.e. 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. Table 1: Base formulation Chinese name Pharmaceutical name Amount (gm)

Huang Qi Radix astragali 9 Yi Mu Cao Herba leonuri heterophylli 9 Sheng Di Radix rehmanniae 9 San Qi Radix pseudoginseng 6 He Shou Wu Radix polygoni multiflori 9 Pu Huang Pollen typhae 9

Example 2: Case Study 1

This patient (age 43 years) had a history of very heavy periods since puberty at age 17. Ultrasound revealed some small fibroids (around 2 cms) but these have not grown over the last 5 years. Blood tests revealed normal hormone levels, but her haemoglobin was usually low i.e. she was anaemic.

Periods - flow lasts for 7 days. Flow is very heavy for 3 days - flooding of bright red blood with large clots. She experiences dragging pain, which can be excruciating, requiring painkillers.

On the first day or two of her period, the patient is exhausted, dizzy and nauseous. The patent can't think clearly and finds it difficult to stand up. She looks extremely pale at this time.

The patent is always struggling with anaemia and has at times been recommended to have blood transfusions. She takes iron supplements always. She was prescribed the following formula:

Chinese name Pharmaceutical name Amount (gm)

Huang Qi Radix astragali 9

Yi Mu Cao Herba leonuri heterophylli 9 Sheng Di Radix rehmanniae 9

San Qi Radix pseudoginseng 6

He Shou Wu Radix polygoni multiflori 9

Pu Huang Pollen typhae 9

Her next two periods were shorter (i.e. stopped soon after day 3) but the first day was still very heavy. By the third cycle of treatment she reported her period was remarkably improved. The flow was much lighter and she did not feel as exhausted and sick. The dragging pain was also gone. She was instructed to continue the formula for another 2 cycles to consolidate the result.

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.