WO2001022980A1

WO2001022980A1 - Side effects treatment

Info

Publication number: WO2001022980A1
Application number: PCT/AU2000/001159
Authority: WO
Inventors: David Rudov
Original assignee: Individual
Current assignee: Individual
Priority date: 1999-09-24
Filing date: 2000-09-25
Publication date: 2001-04-05
Anticipated expiration: 2002-03-24
Also published as: GB0206401D0; GB2369299A; DE10085032T1

Abstract

The invention provides a novel use of a substance comprising a pharmaceutically acceptable liquid extract from a juice derived from cereal plants (which includes wild grasses) and carried in a pharmaceutically acceptable carrier or excipient for application to and take up by an animal subject. The use is for the manufacture of a product for the adjunct treatment of animals including humans, to reduce the incidence or severity of side effects associated with primary chemical treatment of the animal. The invention also provides a product for the adjunct treatment of animals, a process for the adjunct treatment of animals, an adjunct secondary treatment product effective to reduce the incidence or severity of side effects, and a process for enhancing the therapeutic treatment of an animal.

Description

SIDE EFFECTS TREATMENT

This invention relates to processes and products for the treatment of animals,

including humans, to reduce side effects associated with other chemical treatment regimes.

The treatment of animals including veterinary treatment of domestic animals, sporting

animals such as race horses, and livestock by use of chemical substances (including systemic and local treatments by ingestion. intravenous, and subcutaneous application as

well as by external or topical application) frequently leads to undesirable side effects of the

treatment regime. There is a very wide range of such side effects such as effects caused by

systemic circulation of the treatment substances or caused by by-products or caused by

reaction products. Such side effects include for example rashes, headaches, nausea,

dizziness, vision difficulties, circulatory problems and disorders, as well as general or local

sensations of pain. Other side effects include gastrointestinal problems, e.g. reflux,

indigestion, gas production and eructation, constipation, diarrhoea. The side effects can be

due to toxic or allergic reactions by the subject as well as being effects of the mechanisms of the substances. For example, the use of antibiotics is frequently associated with digestive

problems when taken by ingestion due to the action of the antibiotics in inhibiting or killing

normally present and beneficial micro-organisms in the digestive tract. .

Antibiotics are frequently prescribed and used in the treatment of animals, including

humans, for micro-organism infections, particularly bacterial infections and undesired side

effects of the antibiotics of the general kind outlined above are observed. Such side effects

frequently require separate treatment, such as treatment with antihistamines to manage mild

allergic responses.

The condition known as "chronic fatigue syndrome" or "CFS" is believed to be

caused or associated with bacterial infection and is therefore known to be treated with antibiotics. Undesired side effects are therefore associated with treatment of CFS patients

with antibiotics.

The administration of antibiotics to animals, including human patients, both before, during and after surgery or other interventions including intrusive examinations is common. Such administration of antibiotics is carried out to avoid or reduce trauma that may be

commonly associated with the procedures. For example, respiratory infections, including

bacterial and viral infections, are commonly encountered in post operative patients because

patients are more susceptible at such times due to the immune system being compromised or more vulnerable following the traumatic procedures and due also to the condition for which

the procedure has been carried out. The administration of antibiotics in such circumstances

is a frequently used as a precautionary measure. The antibiotics are frequently administered

intravenously together with other substances such as saline solutions, analgesics, sedatives.

The administration of antibiotics or other chemical treatments as precautionary or

preventative treatments before, during or after traumatic events or during immuno

compromised or vulnerable conditions can be associated with the undesired side effects of

the kind discussed above.

It is an object of the present invention to provide methods and products for reducing

the incidence or severity of undesired side effects associated with chemical treatments of

animals, including humans.

According to the present invention there is provided a method of treating an animal, including a human, e.g. for a pathological or injured or abnormal condition or for

precautionary or preventative treatment before during or after a traumatic event or immuno

compromised or vulnerable condition of the animal, the method including a primary

chemical treatment involving the administration of a primary substance, the primary treatment substance being selected from the group of treatment substances for animals

including antibiotics and other pharmacologically effective substances for treating animals, the administration of such primary substance being commonly or occasionally associated with undesirable side effects being experienced by the animal, the method of treating further comprising administering to the animal, in conjunction with the administration of the

primary treatment substance, a pharmacologically or therapeutically effective amount of a

secondary substance to reduce the incidence or severity of the side effects, the secondary

substance including an extract from cereal plants, the extract comprising a pharmaceutically

acceptable extract derived from juice of cereal plants, the extract being carried in a

pharmaceutically acceptable base carrier or excipient enabling the secondary substance to be

taken up by the animal being treated.

The treatment of an animal, including a human, with a primary treatment substance

having undesirable side effects with the secondary substance as an adjunct to the primary

treatment is based on the unexpected and surprising reduction of the incidence or severity of

the side effects resulting apparently from the adjunct treatment. For example, it has been

observed that in the treatment of CFS using antibiotics, the normally or occasionally

expected and observed side effects of the antibiotic treatment regime were significantly

reduced in subjects having the adjunct treatment with the secondary substance according to

the process of the present invention.

Likewise, it has been observed that the treatment of race horses for injured or

pathological conditions involving administration of chemical substances such as antibiotics,

has frequently necessitated the horses being rested or "spelled" or "turned out" for several

months due to side effects of the primary treatment. However the administration of a

secondary substance in accordance with the present invention to the animals as an adjunct to the primary treatment has surprisingly led to horses following thorough veterinary inspections being declared fit to be raced again after much shorter resting or spelling

periods.

Broadly the secondary substance used in the present invention comprises a

pharmaceutically acceptable liquid extract from a juice derived from cereal plants (which

includes wild grasses) and carried in a pharmaceutically acceptable carrier or excipient for

application to and take up by an animal subject. Such a substance will be referred to in this specification as "a substance of the kind described".

The references throughout this specification to a primary chemical treatment are

intended to cover any treatment with a foreign substance or material, whether by external,

topical, transdermal. subcutaneous, intravenous application or by ingestion, the foreign

substance or material including pharmaceuticals, herbal or naturopathic substances, and

organic and inorganic elements or compounds, and carriers or excipients therefor.

According to a first particular aspect of the present invention, there is provided a

novel use of the substance of the kind described for the manufacture of a product for the

adjunct treatment of animals including humans, to reduce the incidence or severity of side

effects associated with primary chemical treatment of the animal.

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

product for the adjunct treatment of animals, including humans, the product comprising a

substance of the kind described in an effective quantity to reduce the incidence or severity

of side effects associated with primary chemical treatment of the animal.

In a third particular aspect of the present invention there is provided a process for the

adjunct treatment of animals, including humans, undergoing a primary chemical treatment,

the process including the steps of administering an effective quantity of a substance of the kind described to the animal in a manner and over a period of time to reduce the incidence

or severity of side effects associated with primary chemical treatment of the animal.

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

an adjunct secondary treatment product effective to reduce the incidence or severity of side

effects associated with primary chemical treatment of the animal, the product comprising a substance of the kind described provided in a concentration and medium for administration

to the animal to achieve the side effect reduction.

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

enhancing a therapeutic treatment of an animal by reducing the incidence or severity of side

effects associated with a primary chemical treatment of the animal, the process comprising

administering to the animal a substance of the kind described in a quantity and over a period

of time to be effective to achieve the side effect reduction.

Preferably in the processes of the invention the administration of the adjunct

secondary treatment substance occurs simultaneously with, and may also be continued after,

the primary chemical treatment period.

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

specification No. AU-81985/87 (Patent No. 599725) (equivalent US Pat. No. 4.943,433) 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 activit} of the

substance of the kind described to reduce the incidence or severity of side effects associated

with primary chemical treatment of the animal 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.

References herein to "cereal plants" is to be interpreted to include wild grasses. 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, T. compactum. or 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.

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. Benzyl alcohol is a suitable carrier component for

transdermal take up of the active ingredients.

The carrier for the extract may comprise the same carrier as used for the primary

chemical treatment. For example, antibiotics can be administered to an animal in a lotion or

cream to be applied topically or externally. In such a case the substance of the kind described can be mixed with the primary treatment substance in the same carrier for

simultaneous administration. Likewise, antibiotics or other primary treatment substances

can be administered intravenously and. subject to obvious precautions concerning

composition and concentrations, the substance of the kind described can be mixed with the intravenous solution for simultaneous administration. Of course, it will be appreciated that the primary treatment substance and secondary treatment substance can be administered

separately in their respective carriers, e.g. the primary substance intravenously and the secondary substance transdermal ly. or the primary substance by ingestion and the secondary substance by sublingual administration and transdermal absorbtion through oral mucous

tissues.

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 between 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 reduce the incidence or severity of side

effects associated with primary chemical treatment of the animal is preferably by external

application so that the substance is taken up by the body by absorption through the skin or mucous tissues. 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. A suitable

formulation is available commercially under the registered trade mark Oralmat,

manufactured by Schumacher Pharmaceuticals Pty Ltd of Melbourne, Australia. This formulation can be taken sublingually. three drops taken three times daily, to achieve the

described beneficial effects.

It may also be possible (subject to obvious safeguards concerning the composition

and concentration of the substance and carrier) to administer the substance subdermally by

implant or injection.

The reduction of the incidence or severity of side effects associated with primary

chemical treatment of the animal was unexpected and surprising and as yet the mechanism

for this activity has not been determined. Indeed no obvious possible mechanism for the

observed side effect reducing 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 that activity.

The described effects of reducing incidence or severity of side effects have been observed in use of the secondary substance as a simultaneous adjunct treatment of patients

being treated for chronic fatigue syndrome with a primary treatment substance in the nature

of an antibiotic.

The accelerated recovery with reduced or shortened incidence or severity of side

effects has been observed in race horses undergoing primary chemical treatment for injury

or pathological conditions. These observed examples of reduction of the incidence or severity of side effects in

chronic fatigue syndrome patients and in race horses indicate applicability of the present invention as an adjunct treatment for an animal, including a human, being treated for a

pathological or injured or abnormal condition involving administration of a primary

chemical treatment, particularly antibiotics. However, the observed advantageous effects in

side effects reduction indicates that the present invention is also applicable as a

precautionary or preventative treatment, e.g. before, during or after a traumatic event or

before, during or after an observed or expected immuno compromised or vulnerable condition, e.g. pre or post operative periods. The adjunct treatment of an animal according

to the present invention promises a substantial reduction or amelioration of side effects in

such circumstances.

Claims

1. The use of a secondary substance for the manufacture of a product for the adjunct treatment of animals including humans to reduce the incidence or severity of side effects

associated with a primary chemical treatment of the animal, the secondary substance

comprising a pharmaceutically acceptable liquid extract from a juice derived from cereal

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

and take up by an animal subject.

2. The use as claimed in claim 1 wherein the juice is derived from rye grass (Secale Cereale).

3. The use as claimed in claim 1 or 2 wherein the extract is obtained from juice derived

from the green leafy parts of the plants harvested when the plants are at the unjointed or

immature development stage.

4. The use as claimed in any one of the preceding claims wherein the liquid extract

comprises substantially only the water soluble components of the juice.

5. The use as claimed in any one of the preceding claims wherein the product includes

both the secondary substance for the adjunct treatment mixed in the same carrier or

excipient as the primary substance used for the primary chemical treatment whereby both

the primary treatment substance and the secondary substance are administered to the subject

simultaneously.

6. The use as claimed in claim 5 wherein the primary treatment substance comprises an antiobiotic in a carrier or excipient for topical or external application to the subject, the

secondary substance being mixed in the same carrier or excipient.

7. A substance for the adjunct treatment of animals including humans to reduce the

incidence or severity of side effects associated with a primary chemical treatment of the animal, the secondary substance comprising a pharmaceutically acceptable liquid extract

from a juice derived from cereal plants and carried in a pharmaceutically acceptable carrier or excipient for application to and take up by an animal subject.

8. A substance as claimed in claim 7 wherein the juice is derived from rye grass (Secale

Cereale).

9. A substance as claimed in claim 7 or 8 wherein the extract is obtained from juice

derived from the green leafy parts of the plants harvested when the plants are at the

unjointed or immature development stage.

10. A substance as claimed in any one of claims 7 to 9 wherein the liquid extract comprises

substantially only the water soluble components of the juice.

1 1. A substance as claimed in any one of claims 7 to 10 wherein the product includes both the secondary substance for the adjunct treatment mixed in the same carrier or excipient as

the primary substance used for the primary chemical treatment whereby both the primary

treatment substance and the secondary substance are administered to the subject simultaneously.

12. A substance as claimed in claim 1 1 wherein the primary treatment substance comprises

an antibiotic in a carrier or excipient for topical or external application to the subject, the secondary substance being mixed in the same carrier or excipient.

13. A method of treating an animal, including a human, e.g. for a pathological or injured or

abnormal condition or for precautionary or preventative treatment before during or after a

traumatic event or immuno compromised or vulnerable condition of the animal, the method

including a primary chemical treatment involving the administration of a primary substance,

the primary treatment substance being selected from the group of treatment substances for

animals including antibiotics and other pharmacologically effective substances for treating animals, the administration of such primary substance being commonly or occasionally associated with undesirable side effects being experienced by the animal, the method of treating further comprising administering to the animal, in conjunction with the administration of the primary treatment substance, a pharmacologically or therapeutically

5 effective amount of a secondary substance to reduce the incidence or severity of the side

effects, the secondary substance including an extract from cereal plants, the extract

comprising a pharmaceutically acceptable extract derived from juice of cereal plants, the extract being carried in a pharmaceutically acceptable base carrier or excipient enabling the

secondary substance to be taken up by the animal being treated.

10 14. A method as claimed in claim 13 wherein the juice is derived from rye grass (Secale

Cereale).

15. A method as claimed in claim 13 or 14 wherein the extract is obtained from juice

unjointed or immature development stage.

15 16. A method as claimed in any one of claims 13 to 15 wherein the liquid extract comprises substantially only the water soluble components of the juice.

17. A method as claimed in any one of claims 13 to 16 wherein the administration of the

secondary substance occurs at least simultaneously with the administration of the primary

treatment substance.

0 18. A method as claimed in any one of claims 13 to 17 wherein the administration of the

secondary substance comprises external application to the animal of the secondary

substance so that the secondary substance is taken up by the body by absorption through the

skin or mucous tissues.

19. A method as claimed in claim 18 wherein the secondary substance is administered sub-lingually by administering the secondary substance orally to be held in the mouth and

under the tongue.

20. A method as claimed any one of claims 13 to 19 wherein the primary substance 5 comprises an antibiotic substance.

21. A method as claimed in claim 20 wherein the animal comprises a human being treated

for chronic fatigue syndrome b\ the administration of the antibiotic substance.

22. A method as claimed in claim 20 wherein the animal is a human undergoing treatment by administration of the antibiotic substance pre or post surgical procedure or intrusive

10 examination.

23. An adjunct secondary treatment substance for the adjunct treatment of animals including humans to reduce the incidence or severity of side effects associated with a

primary chemical treatment of the animal, the secondary substance comprising a

pharmaceutically acceptable liquid extract from a juice derived from cereal plants and

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

by an animal subject, the liquid extract being provided in a concentration for administration

to the animal to achieve the side effect reduction.

24. An adjunct secondary treatment substance as claimed in claim 23 wherein the juice is

derived from rye grass (secale cereale).

20 25. An adjunct secondary treatment substance as claimed in claim 23 or 24 wherein the

extract is obtained from juice derived from the green leafy parts of the plants harvested

when the plants are at the unjointed or immature development stage.

26. An adjunct secondary treatment substance as claimed in any one of claims 23 to 25

wherein the liquid extract comprises substantially only the water soluble components of the

juice.

27. An adjunct secondary treatment substance as claimed in any one of claims 23 to 26

wherein the product includes both the secondary substance for the adjunct treatment mixed in the same carrier or excipient as the primary substance used for the primary chemical

treatment whereby both the primary treatment substance and the secondary substance are

administered to the subject simultaneously.

28. An adjunct secondary treatment substance as claimed in claim 27 wherein the primary

treatment substance comprises an antibiotic in a carrier or excipient for topical or external

application to the subject, the secondary substance being mixed in the same carrier or

excipient.

29. A method of enhancing the therapeutic treatment of an animal, including a human, e.g.

for a pathological or injured or abnormal condition or for precautionary or preventative treatment before during or after a traumatic event or immuno compromised or vulnerable

condition of the animal, by reducing the incidence or severity of side effect associated with

a primary chemical treatment involving the administration of a primary substance, the

method comprising administering to the animal, in conjunction with the administration of

the primary treatment substance, a pharmacologically or therapeutically effective amount of

a secondary substance to reduce the incidence or severity of the side effects, the secondary

pharmaceutically acceptable base carrier or excipient enabling the secondary substance to be taken up by the animal being treated, the secondary substance administered being in a quantity and over a period of time to be effective to achieve the side effect reduction.

30. A method as claimed in claim 29 wherein the juice is derived from rye grass (Secale

Cereale). 5

31. A method as claimed in claim 29 or 30 wherein the extract is obtained from juice

unjointed or immature development stage.

32. A method as claimed in any one of claims 29 to 31 wherein the liquid extract comprises substantially only the water soluble components of the juice.

10 33. A method as claimed in any one of claims 29 to 32 wherein the administration of the

treatment substance.

34. A method as claimed in any one of claims 29 to 33 wherein the administration of the

15 substance so that the secondary substance is taken up by the body by absorption through the

skin or mucous tissues.

35. A method as claimed in claim 34 wherein the secondary substance is administered

sub-lingually by administering the secondary substance orally to be held in the mouth and

under the tongue.

20 36. A method as claimed any one of claims 29 to 35 wherein the primary substance

comprises an antibiotic substance.

37. A method as claimed in claim 36 wherein the animal comprises a human being treated

for chronic fatigue syndrome by the administration of the antibiotic substance.

38. A method as claimed in claim 36 wherein the animal is a human undergoing treatment

by administration of the antibiotic substance pre or post surgical procedure or intrusive

examination.