WO2000064461A1

WO2000064461A1 - Treatment for improving lung function

Info

Publication number: WO2000064461A1
Application number: PCT/AU2000/000379
Authority: WO
Inventors: David Rudov
Original assignee: David Rudov
Priority date: 1999-04-27
Filing date: 2000-04-27
Publication date: 2000-11-02
Also published as: AUPP999699A0

Abstract

Liquid extracts from a juice derived from cereal plants, particularly rye grass, are used to augment or enhance lung function in mammalian subjects, including humans, either for performance enhancing results or for therapeutic purposes.

Description

TREATMENT FOR IMPROVING LUNG FUNCTION Background of the invention

This invention relates to treatments for improving lung function including processes

and substances for enhancing or augmenting lung function in mammals. The lung function of a mammal, such as a human, includes gas uptake or transfer,

particularly uptake of oxygen by the bloodstream through the lungs and release of carbon

dioxide as well as lung capacity and gas expulsion parameters. The effectiveness or

efficiency of lung function varies considerably between individuals and can be impaired or

reduced or below average or below a desired level or performance due to both genetic

factors and environmental and internal physiological factors including traumatised lung

conditions and pathological conditions. Enhancing or augmenting lung function has many

benefits ranging from marginal performance enhancing improvements, e.g. for athletes,

through to relief or amelioration of abnormal conditions including pathological conditions of the lungs.

Enhancing or augmenting lung function in mammals can be achieved in various ways.

For example, physical exercise, particularly aerobic exercises, can help to enhance or augment lung function. For some abnormal lung conditions, some physiotherapy regimes are used such as massage and such as coughing and breathing exercises to help dislodge and

remove fluid or mucous accumulations. There are drugs available for alleviating the effects

of conditions associated with poor or compromised lung function, but these are frequently

based on substances to dilate gas passages, such as steroid based drugs. Such drugs may not

have any effect in enhancing or augmenting lung function and/or they may have undesirable

side effects either in the short or longer term. Summary of the invention

It is an object of the present invention to provide firstly substances, secondly the novel

manufacture of such substances, and thirdly processes for enhancing or augmenting lung function in mammals. The present invention is based on the unexpected and surprising property of enhancing

or augmenting lung function found in an extract from cereal plants, the extract comprising a

pharmaceutically acceptable extract derived from juice of cereal plants, preferably young plants at the unjointed stage of plant development, the extract being carried in a

pharmaceutically acceptable base carrier or excipient which is taken up by the mammalian

subject.

Broadly the substance used in the present invention comprises a pharmaceutically

acceptable liquid extract derived from cereal plants and carried in a pharmaceutically

acceptable carrier or excipient for application to and take up by a mammalian subject. Such

a substance will be referred to in this specification as "a substance of the kind described".

According to a first aspect of the present invention, there is provided a novel use of a cereal plant extract for the manufacture of a product for the treatment of mammalian subjects

to enhance or augment the lung function of the subjects, the treatment being either for

physical performance enhancment or for a therapeutic effect, the cereal plant extract

comprising a pharmaceutically acceptable liquid extract derived from cereal plants which is

carried in a pharmaceutically acceptable carrier or excipient for application to and take up by

the subjects.

According to a second aspect of the present invention there is provided a method of

enhancing or augmenting the lung function of a mammalian subject, the process including the

steps of administering an effective quantity of a cereal plant extract to the mammalian subject in a manner and over a period of time so as to enhance or augment the lung function of the

subject, the cereal plant extract comprising a pharmaceutically acceptable liquid extract

derived from cereal plants and carried in a pharmaceutically acceptable carrier or excipient for application to and take up by the mammalian subject. In a third aspect of the present invention there is provided a treatment product for

enhancing or augmenting lung function of a mammalian subject and comprising a cereal plant extract in an effective quantity for achieving when administered to the mammalian subject the

enhancement or augmentation of lung function of the subject, the cereal plant extract

comprising a pharmaceutically acceptable liquid extract derived from cereal plants and

the mammalian subject.

In accordance with a fourth aspect of the present invention there is provided a physical

performance enhancing product effective to enhance or augment a lung function of a

mammalian subject, the product comprising a cereal plant extract provided in a concentration

and medium for administration to the mammalian subject to achieve the enhanced or

augmented lung function, the cereal plant extract comprising a pharmaceutically acceptable liquid extract derived from cereal plants and carried in a pharmaceutically acceptable carrier

or excipient for application to and take up by the mammalian subject.

In a fifth aspect of the present invention there is provided a process for enhancing

physical performance capacity of a mammalian subject by enhancing the lung function of the

subject, the process including the step of administering to the mammalian subject a cereal

plant extract in a quantity and over a period of time to be effective to achieve enhancement

or augmentation of the lung function, the cereal plant extract comprising a pharmaceutically acceptable liquid extract derived from cereal plants and carried in a pharmaceutically acceptable carrier or excipient for application to and take up by a mammalian subject.

In all aspects of the invention, the mammalian subjects may be humans but the invention is also applicable to other animals such as racehorses. Brief Description of the drawings

Figure 1 is a graphical indication of lung function tests in the clinical trial described

later, and Figure 2 is a graphical indication of a qualitative evaluation of results of the clinical trial.

Detailed description of the invention

A substance of the kind described is already known from Australian patent

specification No. AU-81985/87 (Patent No. 599725) (equivalent to US Patent No. 4943433)

by the present applicant. In this prior patent specification, a range of possible uses of the

substance are described or indicated in passing. This earlier patent specification and subsequent uses of the commercial product produced according to the prior patent

specification have resulted in recognition of range of physiological indications including

anti-inflammatory, immunomodulatory, and analgesic activity. However, the activity of the

substance of the kind described in enhancing or augmenting lung function is totally unexpected and surprising leading to novel new uses of the substance hitherto unknown and

with no reason to expect or suspect or seek such new uses.

Reference may be made to AU-81985/87 for further background and description of a

substance of the kind described useable in the present invention in its various aspects.

However, a particular cereal plant found to be particularly useful as a source of the extract is Secale Cereale or "rye grass". Extracts from barley and wheat are also believed to be effective. The wheat may comprise Triticum vulgare or aestivum, T. durum, or T. compactum. Another possible

source of the active substance is the hybrid cereal plant known as triticale. Corn, rice, oats, maize, sorghum and millet may also be effective. Preferably the extract is derived from the green leafy part of the plant, or at least

principally from this part of the plant, although additional green parts such as stalk may be

included. The leaves of the plant are preferably treated to yield the extract before the plant

reaches flowering or seed production stage of development. That is, the plant is at its

unjointed or immature development stage.

The extraction is preferably carried out by squeezing, crushing and/or grinding

processes, not by a cutting process, to yield a juice from which the extract is derived. It may

also be possible to extract the actives by steeping the plant material in a solvent, with or

without first disrupting the plant material by squeezing etc., although this process will be

sloλver than the recommended disruption and juice extraction.

Preferably the extract from the cereal plants comprises substantially only the water

soluble components of the juice.

The plant extract may be used in the concentration in which it is derived from the plants.

Alternatively, if desired, the extract may be concentrated and some or substantially all the

liquid content of the plant extract may be removed. For example, the extracted plant matter may be dried, such as by spray drying to yield a powder for mixing with the carrier. The

spray drying is preferably carried out at a temperature of about 50°C and preferably below

60°C. Other possible stabilisation processes for the juice include partial concentration of the derived juice to provide a concentrated liquid, freeze drying of the derived juice, and

blending the derived juice with a preserving agent forming an ingredient of the carrier

Preferably the stabilisation or mixing with the carrier or both is carried out within a

short time and preferably within two hours after extraction

In an alternative possibility the extract may be produced by firstly drying plant matter

after which the dried material is comminuted to yield a powder which includes ingredients

originally in the juice

The carrier for the extract may be any suitable material such as a liquid (e g water or

other solvent), cream, lotion, oil, gel or powder For example the carrier may comprise a

liquid in which the extract is dissolved or vanishing cream which is intended to be absorbed

through the skin when applied so as to thereby carry the plant extract into sub-cutaneous

tissue A water based or aqueous carrier capable of carrying water soluble ingredients to

sub-surface tissues is preferred

Preferably the carrier includes an anti-microbial agent so as to kill or at least inhibit

growth, reproduction or activity of contaminating organisms that may be present in the plant

extract or may be introduced during production of the substance Preferably the

anti-microbial agent is an anti-bacterial agent In addition or alternatively the agent may

have anti-fungal and anti-yeast properties The anti-microbial agent may be added to the

substance during production or may be present in the carrier if the carrier for example is a

standard commercially available product The anti-microbial agent is preferably active to inhibit any activity of organisms and thereby is operative to inhibit spoilage of the substance, e g spoilage of the product when being stored by the user or by a commercial outlet If the anti-microbial is not provided, it is preferred that the extract is substantially sterile when mixed with the carrier. The plants from which the extract is derived may be grown

hydroponically for example under sterile conditions to prevent the introduction of micro-organisms at that stage. The subsequent harvesting and processing may also be carried out under sterile conditions.

The ratio of the extract to the carrier may be anywhere within a large range of possible

ratios. For example the ratio of base carrier to plant extract (and other additives if provided)

may be anywhere betλveen 1 to 5 and 200 to 1 (by weight). A range of 1 to 30% by weight

of extract is preferred.

Preferably the substance has a generally neutral pH in the range 6.0 to 8.0. For

example, the pH may be in the range 6.5 to 7.5.

Use of the substance of the kind described to enhance or augment lung function is

preferably by external application so that the substance is taken up by the body by absorption

through the skin. A particularly preferred method of transdermal uptake is by applying the

substance to the mouth for uptake through mucous tissues of the mouth. For example, the

substance may be administered sublingually, e.g. in the form of drops of the substance taken

orally and held in the mouth under the tongue for a short time. It is found that this method

of administration is effective for uptake of the substance into the body. However, it may also be possible (subject to obvious safeguards concerning the composition of the substance

and carrier) to administer the substance subdermally by implant or injection.

The use of a substance of the kind described to enhance lung function has been

demonstrated by a clinical trial using adult asthmatics categorised as mild or moderate

sufferers from the condition. Clinical trial results

A number of the subjects selected randomly were assigned to respective treatment

groups. One group was provided with a product containing a substance according to the present invention in a liquid form to be taken in a few drops twice or three times daily sublingually. The substance was a rye grass extract in a liquid carrier which is a

commercially available product sold under the trade mark ORALMAT and available from

Schumacher Pharmaceuticals Pty Ltd of Melbourne, Australia. The other group was

provided with a placebo in a similar physical form and with the same dosage instructions.

The trial was a blind trial, i.e. with no clinical personnel or patients knowing whether they were receiving the substance or the placebo.

Lung function tests were carried out on all the patients at the start of the trial, after

one week, and again after four weeks. The tests were carried out after Ventolin™ inhalation

to dilate air passages and minimise other influences on the readings. Figure 1 shows the

results of the lung function tests showing a statistically significant enhancement or

augmentation of lung function in the group administered with the substance of the kind

described.

Both the groups (administered with the tested substance and the placebo) showed

significant improvements in lung fuction measured by FEF max (post-Nentolin) but the group administered with the ORALMAT showed changes seen as more highly significant

(p<0.01) than the changes seen in the placebo group (p<0.05).

The subjects were also asked to qualitatively assess their ability to exercise without excessive distress or fatigue. Figure 2 shows the results of this qualitative test. The vertical

axis relates to a scale from "0" meaning "no change", through to "+3" meaning "greatly

improved", and through to "-3" meaning "greatly worse". The results provided a statistically significant improvement in subjectively assessed ability to exercise achieved by the group administered with the substance of the invention-

No noticeable effect on other treatments which the subjects were undertaking were observed, nor were any adverse side effects of taking the substance of the invention observed

during the trial.

The significant enhancement or augmentation of lung function achieved by

administration of the substance of the kind described leads to many potential fields of use

including physical performance enhancing uses, e.g. by athletes and racehorses, by people

wishing to achieve better gas uptake or transfer whether simply to generally improve

wellness, or whether to recover from or ameliorate some trauma or pathological condition.

The enhancement or augmentation of lung function was unexpected and surprising and as yet

the mechanism for the lung function enhancing activity has not been determined. Indeed no

obvious possible mechanism for the observed activity appears from the known physiological activities of the substance according to the prior patent specification AU-81985/87 which

have been seen over about the last ten years that might have suggested or predicted lung function enhancement activity.

Claims

1. The use of a cereal plant extract for the manufacture of a product for the treatment of

mammalian subjects to enhance or augment the lung function of the subjects, the treatment

being either for physical performance enhancment or for a therapeutic effect, the cereal plant

extract comprising a pharmaceutically acceptable liquid extract derived from cereal plants

which is carried in a pharmaceutically acceptable carrier or excipient for application to and

take up by the subjects.

2 The use as claimed in claim 1 wherein the cereal plants from which the extract is

derived comprise rye grass plants (Secale Cereale).

3 The use as claimed in claim 1 or 2 wherein the liquid extract is obtained from green

leafy parts of the cereal plants.

4. The use as claimed in any one of the preceding claims wherein the component parts of

the cereal plants from which the extract is derived are obtained from plants at their unjointed

or immature development stage and before the plants reach flowering or seed production

stages of development.

5. The use as claimed in any one of the preceding claims wherein the parts of the cereal

plants from which the extract is derived are processed by squeezing, crushing and/or grinding

processes to yield a juice from which the extract is derived.

6. The use as claimed in claim 5 wherein the extract obtained from the juice comprises

substantially only water soluble components of the juice obtained from the cereal plants.

7. The use as claimed in any one of the preceding claims wherein the carrier or excipient

for the extract comprises a water based on aqueous carrier capable of carrying water soluble ingredients in the extract to sub-surface tissues of the mammalian subjects.

8. The use as claimed in any one of the preceding claims wherein the extract is substantially sterile when mixed with the carrier or excipient.

9. A method of enhancing or augmenting the lung function of a mammalian subject, the process including the steps of administering an effective quantity of a cereal plant extract to

5 the mammalian subject in a manner and over a period of time so as to enhance or augment

the lung function of the subject, the cereal plant extract comprising a pharmaceutically

acceptable carrier or excipient for application to and take up by the mammalian subject.

10. A treatment product for enhancing or augmenting lung function of a mammalian

10 subject and comprising a cereal plant extract in an effective quantity for achieving when

administered to the mammalian subject the enhancement or augmentation of lung function of

the subject, the cereal plant extract comprising a pharmaceutically acceptable liquid extract derived from cereal plants and carried in a pharmaceutically acceptable carrier or excipient for application to and take up by the mammalian subject.

15 1 1. A physical performance enhancing product effective to enhance or augment a lung

function of a mammalian subject, the product comprising a cereal plant extract provided in a

concentration and medium for administration to the mammalian subject to achieve the

enhanced or augmented lung function, the cereal plant extract comprising a pharmaceutically acceptable liquid extract derived from cereal plants and carried in a pharmaceutically

20 acceptable carrier or excipient for application to and take up by the mammalian subject.

12. A product as claimed in claim 10 or 11 wherein the cereal plants from which the

extract is derived comprise rye grass plants (Secalβ Cereale).

13. A product as claimed in any one of claims 10 to 12 wherein the liquid extract is

obtained from green leafy parts of the cereal plants.

14. A product as claimed in any one of claims 10 to 13 wherein the component parts of

stages of development.

15. A product as claimed in any one of claims 10 to 14 wherein the parts of the cereal

plants from which the extract is derived are processed by squeezing, crushing and/or grinding processes to yield a juice from which the extract is derived.

16. A product as claimed in claim 15 wherein the extract obtained from the juice

comprises substantially only water soluble components of the juice obtained from the cereal

plants.

17. A product as claimed in any one of claims 10 to 16 wherein the carrier or excipient for

the extract comprises a water based on aqueous carrier capable of carrying water soluble

ingredients in the extract to sub-surface tissues of the mammalian subject.

18. A product as claimed in any one of claims 10 to 17 wherein the extract is substantially

sterile when mixed with the carrier or excipient.

19. A process for enhancing physical performance capacity of a mammalian subject by

enhancing the lung function of the subject, the process including the step of administering to

the mammalian subject a cereal plant extract in a quantity and over a period of time to be effective to achieve enhancement or augmentation of the lung function, the cereal plant

and carried in a pharmaceutically acceptable carrier or excipient for application to and take

up by a mammalian subject.

20. A method as claimed in claim 9 or 19 wherein the step of administering the cereal plant extract comprises external application of the extract to the mammalian subject so that

the extract is taken up by the body of the subject by transdermal absorption.

21. A method as claimed in claim 20 wherein the administration of the cereal plant extract

comprises applying the extract orally to the mammalian subject for uptake through mucous

tissues of the mouth of the subject.

22. A method as claimed in claim 21 wherein the step of administering the cereal plant

extract comprises administering the extract sub-lingually, the extract being in the form of

drops taken orally and held in the mouth of the subject under the tongue for a period of time.