Processing

Please wait...

Settings

Settings

Goto Application

1. WO2010052680 - COMPOSITION FOR TREATMENT OF CANCER

Note: Text based on automatic Optical Character Recognition processes. Please use the PDF version for legal matters

[ EN ]

COMPOSITION FOR TREATMENT OF CANCER

FIELD OF THE INVENTION

The present invention relates to the field of natural pharmaceuticals, and more specifically to a natural composition comprising plant extracts for the treatment or prevention of cancer.

BACKGROUND OF THE INVENTION

Cancer is a term used for diseases in which abnormal cells divide without control and are able to invade other tissues. Cancer cells can spread to other parts of the body (metastasis) through the blood and lymph systems.

There are more than 100 types of cancer, including leukemia, lung cancer, liver cancer, breast cancer, colon cancer, glioma, and pancreatic cancer.

Lung cancer forms in tissues of the lung, usually in the cells lining air passages. The two main types are small cell lung cancer and non-small cell lung cancer. Since lung cancer tends to spread or metastasize very early in its course, it is a very life-threatening cancer and one of the most difficult cancers to treat. While lung cancer can spread to any organ in the body, certain organs, particularly the adrenal glands, liver, brain, and bone, are the most common sites for lung-cancer metastasis.

Colon cancer is cancer of the large intestine (colon). About 112,000 people are diagnosed with colon cancer annually, and about 41,000 new cases of rectal cancer are diagnosed each year, according to the American Cancer Society. Most cases of colon cancer begin as small, benign clumps of cells called adenomatous polyps. Over time some of these polyps become colon cancers.

Breast cancer forms in tissues of the breast. It occurs in both men and women, although male breast cancer is rare. There are two main types of breast cancer, ductal carcinoma, which starts in the ducts that move milk from the breast to the nipple, and lobular carcinoma, which starts in the lobules that produce milk. Most breast cancers are of the ductal type. In rare cases, breast cancer can start in other areas of the breast.

Leukemia is a cancer that starts in blood-forming tissue such as the bone marrow and is characterized by an abnormal proliferation of blood cells, usually leukocytes. Leukemia is divided into four categories: myelogenous or lymphocytic, each of which can be acute or chronic.

Primary liver cancer begins in the cells of the liver itself. In the United States, cancer affecting the liver is more commonly metastatic cancer. Cancers that commonly spread to the liver include colon, lung and breast cancers. Primary liver cancer is rarely discovered early and often doesn't respond to current treatments, thus the prognosis is often poor.

Gliomas are primary brain tumors. There are several kinds of gliomas: astrocytomas, which grow anywhere in the brain or spinal cord; brain stem gliomas, which arise in the lowest part of the brain; ependymomas, which develop inside the brain, in the lining of the ventricles, and oligodendrogliomas, which usually grow in the cerebrum

The most common type of pancreatic cancer arises from the exocrine glands and is called adenocarcinoma of the pancreas. The endocrine glands of the pancreas can give rise to a completely different type of cancer, referred to as pancreatic neuroendocrine carcinoma or islet cell tumor. Pancreatic cancer often has a poor prognosis, even when diagnosed early. Pancreatic cancer typically spreads rapidly and is seldom detected in its early stages, which is a major reason why it's a leading cause of cancer death. Signs and symptoms may not appear until pancreatic cancer is quite advanced and surgical removal isn't possible.

The World Health Organization estimates that the worldwide incidence of cancer is set to double from 10 million to 20 million, and the death rate is expected to increase from 6 million to 10 million over the next two decades. According to the American Cancer Society, about 1.5 million new cancer cases are diagnosed annually in the U.S. and over 500 thousand Americans are expected to die from the disease, cancer being the second leading cause of death. The main types of deadly cancer in the US are lung, colon and prostate for men and lung, colon and breast for women. The statistics in Western Europe are similar.

Surgery, chemotherapy and irradiation are the most acceptable treatments for cancer, however, for many cancer patients those therapies offer little hope of recovery. The overall five-year survival rate is currently only about 62%, in spite of the fact that over $60 billion are currently being spent on direct cancer medical costs.

Currently known chemotherapeutic agents cause a wide range of side-effects, including nausea, vomiting, anemia, and hair loss.

There is thus a widely recognized need for, and it would be highly advantageous to have, a composition for treatment or prevention of cancer which is devoid of at least some of the limitations of the prior art.

SUMMARY OF THE INVENTION

The present invention, in at least some embodiments, provides compositions comprising extracts of at least three selected from the group consisting of Petroselinum, Cymbopogon, Citrus, Apium graveolens, Aloysia, Foeniculum, Melissa, Fortunella, Arisaema, and Pelargonium, and uses thereof for the treatment or prevention of cancer.

According to some embodiments, there is provided the use of a composition comprising extracts of at least three selected from the group consisting of Petroselinum, Cymbopogon, Citrus, Apium graveolens, Aloysia, Foeniculum, Melissa, Fortunella, Arisaema, and Pelargonium for the treatment or prevention of cancer.

As used herein, the term "treating" may optionally comprise one or more of preventing, ameliorating, reducing, alleviating, eliminating (partially or completely) or relieving.

According to some embodiments, the at least three extracts comprise Petroselinum (such as, for example, Petroselinum crispum or Petroselinum neapolitanum or combinations thereof), Citrus, and Cymbopogon (such as, for example, Cymbopogon bombycinus, Cymbopogon citratus, Cymbopogon citriodora, Cymbopogon βexuosus, Cymbopogon martinii, Cymbopogon nardus, Cymbopogon obtectus, Cymbopogon procerus, Cymbopogon proximus, Cymbopogon refractus, Cymbopogon schoenanthus, or Cymbopogon winterianus or combinations thereof).

According to some embodiments, the at least three extracts comprise Apium graveolens, Citrus, and Aloysia (such as, for example, Aloysia triphylla, Aloysia dodsoniorum, Aloysia gratissima, Aloysia macrostachya, or Aloysia wrightii or combinations thereof).

According to some embodiments, the at least three extracts comprise Foeniculum, Citrus, and Melissa (such as, for example, Melissa axillaris, Melissa bicornis, Melissa flava, Melissa officinalis, or Melissa yunnanensis, or combinations thereof).

According to some embodiments, the at least three extracts comprise Arisaema

(such as, for example, Arisaema amurense, Arisaema angustatum, Arisaema candidissimum, Arisaema concinnum, Arisaema consanguineum, Arisaema costatum, Arisaema dracontium, Arisaema elephas, Arisaema erubescens, Arisaema fimbriatum, Arisaema flavum, Arisaema grijfithii, Arisaema jacquemontii, Arisaema kiushianum, Arisaema lidaense, Arisaema lihenganum, Arisaema monophyllum, Arisaema nepenthoides, Arisaema peninsulae, Arisaema propinquum, Arisaema ringens, Arisaema robustum, Arisaema serratum, Arisaema sikokianum, Arisaema speciosum, Arisaema thunbergii, Arisaema tortuosum, Arisaema triphyllum, Arisaema undulatifolium, Arisaema undulatifolium, Arisaema thunbergii, Arisaema utile, Arisaema wattii, or Arisaema yamatense, or combinations thereof), Fortunella (such as, for example, Fortunella margarita, Fortunella crassifolia, Fortunella hindsii, Fortunella japonica, Fortunella obovata, or Fortunella polyandra, or combinations thereof), and Pelargonium.

According to some embodiments, Citrus may comprise one or more of Citrus aurantifolia, Citrus medica, Citrus reticulata, Citrus aurantium, Citrus latifolia, Citrus limon, Citrus limonia, Citrus paradisi, Citrus sinensis, Citrus tangelo, Citrus nobilis, Citrus Clementina, Citrus reshni, Citrus unshiu, Citrus limetta, Citrus limettiodes, Citrus latifolia, Citrus jambhiri, Citrus depressa, Citrus sudachi, and Citrus volkameriana.

According to some embodiments, the composition comprises extracts of Petroselinum crispum, Citrus reticulata and Cymbopogon citratus

According to some embodiments, the extract Petroselinum crispum is obtained from the root of the plant. Optionally and preferably, the extract is an alcohol extract. Optionally and more preferably, the alcohol extract of root of Petroselinum crispum is present in the composition at a concentration at a in the range of from about 20% to about 60% (v/v) of the total composition, and more preferably the concentration is about 40% of the total composition.

According to some embodiments, the extract of Citrus reticulata is obtained from the peel of the fruit. Optionally and preferably, the extract of peel of Citrus reticulata comprises an alcohol extract. Optionally and more preferably, the alcohol extract of peel of Citrus reticulata is present in the composition at a concentration in the range of from about 10% to about 30% (v/v) of the total composition, and more preferably, the concentration is about 20% of the total composition.

According to some embodiments, the extract of Cymbopogon citratus comprises an essential oil. Optionally and preferably, the essential oil of Cymbopogon citratus is obtained by steam distillation. Optionally and more preferably, the essential oil of Cymbopogon citratus is present in the composition at a concentration in the range of from about 20% to about 60% (v/v) of the total composition, and more preferably, the concentration is about 40%.

According to some embodiments, the composition comprises about 40% Petroselinum crispum, about 20% Citrus reticulate and about 40% Cymbopogon citratus.

According to some embodiments, the composition comprises extracts of Apium graveolens, Citrus aurantium or Citrus sinensis, and Aloysia triphylla.

According to some embodiments, the extract of Apium graveolens is obtained from the root of the plant. Optionally and preferably, the extract of root of Apium graveolens is an alcohol extract.

According to some embodiments, the extract of Citrus aurantium or Citrus sinensis is obtained from the peel of the fruit. Optionally and preferably, the extract of peel of Citrus aurantium or Citrus sinensis comprises an alcohol extract.

According to some embodiments, the extract of Aloysia triphylla comprises an essential oil. Optionally and preferably, the essential oil is obtained by steam distillation.

According to some embodiments, the composition comprises Foeniculum vulgar e, Citrus limon, and Melissa officinalis.

According to some embodiments, the extract of Foeniculum vulgar e is obtained from the root of the plant. Optionally and preferably, the extract of Foeniculum vulgare comprises an alcohol extract.

According to some embodiments, the extract of Citrus limon is obtained from the peel of the fruit. Optionally and preferably, the extract of peel of Citrus limon comprises an alcohol extract.

According to some embodiments, the extract of Melissa officinalis comprises an essential oil. Optionally and preferably, the essential oil of Melissa officinalis is obtained by steam distillation.

According to some embodiments, the composition comprises Arisaema triphyllum, Fortunella margarita, and Pelargonium crispum.

According to some embodiments, the extract of Arisaema triphyllum is obtained from the root of the plant. Optionally and preferably, the extract of root of Arisaema triphyllum comprises an alcohol extract.

According to some embodiments, the extract of Fortunella margarita is obtained from the peel of the fruit. Optionally and preferably, the extract of peel of Fortunella margarita comprises an alcohol extract.

According to some embodiments, the extract of Pelargonium crispum comprises an essential oil. Optionally and preferably, the essential oil of Pelargonium crispum is obtained by steam distillation.

According to some embodiments, the cancer treated by the composition of the present invention is at least one of leukemia, lung cancer, liver cancer, breast cancer, colon cancer, glioma, and pancreatic cancer.

The present invention further provides a method of treating cancer, the method comprising administering to a patient in need thereof a composition comprising extracts of at least three of Petroselinum, Cymbopogon, Citrus, Apium graveolens, Aloysia, Foeniculum, Melissa, Fortunella, Arisaema, and Pelargonium.

Optionally and preferably, the composition is administered orally.

According to some embodiments, the composition comprises an isomer of an aldehyde of citral (3,7-dimethyl-2,6-octadienal), such as neral (citral B) or geranial

(citral A), linalyl aldhehyde, vitamin A, vitamin C, iron, vitamin Bl, isopropenyltoluene, hesperidin, limonene, elmene, copanene, b-sesquiphellandrene, and carotene.

According to some embodiments, the composition comprises at least one phenol, at least one terpene, at least one flavonoid and at least one vitamin.

According to some embodiments, the composition comprises at least one terpene aldehyde, vitamin A, vitamin C, iron, vitamin Bl, isopropenyltoluene, hesperidin, limonene, elmene, copanene, b-sesquiphellandrene, and carotene.

According to some embodiments, the at least one phenol comprises myristicin, eugenol, and apiole.

According to some embodiments, the at least one terpene comprises beta phellandrene, limonene and alpha-thujene.

According to some embodiments, the at least one flavonoid comprises crisoeriol, apigenin, apiin and leuteolin.

According to some embodiments, the composition comprises comprises myristicin, apiole, beta phellandrene, limonene, eugenol, alpha-thujene, crisoeriol, apigenin, apiin, leuteolin, beta carotene, folic acid, B vitamins, and Pyrroloquinoline quinone.

Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, suitable methods and materials are described below.

Where ranges are given, endpoints are included within the range. Furthermore, it is to be understood that unless otherwise indicated or otherwise evident from the context and understanding of one of ordinary skill m the art. values that are expressed as a range can assume any specific value or subrange within the stated range in different embodiments of the invention, to the tenth of the unit of the lower limit of the range, unless the context clearly dictates otherwise. Where a percentage is recited in reference to a value that intrinsically has units that are whole numbers, any resulting fraction may be rounded to the nearest whole number.

In case of conflict, the patent specification, including definitions, will control. In addition, the materials, methods, and examples are illustrative only and not intended to be limiting.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

The present invention, according to at least some embodiments, provides use of a composition comprising extracts of at least three of Petroselinum, Cymbopogon, Citrus, Apium graveolens, Aloysia, Foeniculum, Melissa, Fortunella, Arisaema, and Pelargonium for the treatment or prevention of cancer.

Petroselinum (parsley) is a bright green, biennial herb, commonly used as a spice. There are more than 30 varieties; the most well known being the curly leaf and Italian, or flat leaf (Petroselinum neapolitanum). Parsley is known to contain important minerals, beta-carotene, essential oils (including eugenol and apiole), flavonoids, coumarins, chlorophyll, B-vitamins and vitamins A, C, E and K. Parsley teas have been used mainly as kidney stone, bladder infection, and jaundice medications, as well as digestive aids.

Cymbopogon is a genus of about 55 species of grasses, native to warm temperate and tropical regions. The genus includes lemongrass (Cymbopogon citratus), which is widely us an herb in Asian and Caribbean cookery. The grass is considered a diuretic, tonic and stimulant. It promotes good digestion, and a preparation of lemon grass with pepper has been used for relief of menstrual troubles and nausea. It induces perspiration, to cool the body and reduce a fever. It is well known as a mild insect repellent and the essential oil is used in perfumery.

Citrus is a genus of flowering plants originating in tropical and subtropical southeast regions of the world. Natural and cultivated origin hybrids include commercially important fruit such as oranges, grapefruit, lemons, limes, mandarins, and tangerines. Citrus fruits are notable for their fragrance, partly due to flavonoids and limonoids (which in turn are terpenes) contained in the rind, and most are juice-laden. The juice contains a high quantity of citric acid giving them their characteristic sharp flavour. They are also good sources of vitamin C and flavonoids.

Apium graveolens (celery and celeraic) is used around the world as a vegetable. Celery contains vitamins A, Bl, B2, B6, C, E, K, PP and minerals such as iron, calcium, phosphorus, magnesium and zinc. The plant has diuretic properties and dichloridic effects which are useful in renal afflictions (such as renal colic and renal lithiasis) and heart disorders.

Aloysia is a genus of about 35 species of aromatic flowering shrubs. The best known species is Aloysia triphylla (lemon verbena). Lemon verbena leaves are used to add a lemony flavour to fish and poultry dishes, vegetable marinades, salad dressings, jams, puddings, and beverages. It also is used to make herbal teas. In addition, lemon verbona is known to have anti-Candida albicans activity. The major isolates in lemon verbena oil are citral, nerol and geraniol.

Foeniculum is a genus of fewer than half a dozen species, the best known of which is Foeniculum vulgar e (fennel). Fennel contains various phytonutrients, including the flavonoids rutin, quercitin, and various kaempferol glycosides that give it strong antioxidant activity. It is carminative, a weak diuretic and mild stimulant.

Melissa is a genus of five species of perennial herbs native to Europe and Asia, the most commonly grown of which is Melissa officinalis (lemon balm). The crushed leaves, when rubbed on the skin, are used as a repellant for mosquitos.

Lemon balm is also used medicinally as a herbal tea, or in extract form. It is claimed to have antibacterial, antiviral properties (particularly against herpes simplex), and it is also used as a mild sedative or calming agent. Lemon Balm contains eugenol which kills bacteria and has been shown to calm muscles and numb tissues. It also contains tannins that contribute to its anti-viral effects, as well as terpenes that add to its soothing effects.

Fortunella is a genus related to Citrus in the flowering plant family Rutaceae, and comprising five species: Fortunella crassifolia (Meiwa Kumquat), Fortunella hindsii (Hong Kong Kumquat), Fortunella japonica (Marumi or Nagami Kumquat),

Fortunella obovata (Jiangsu or Fukushu Kumquat) and Fortunella polyandra

(Malayan Kumquat).

Arisaema is a genus of about 150 species in the flowering plant family Araceae, native to eastern and central Africa, Asia and eastern North America. The best known species is Arisaema triphyllum (Jack in the pulpit). A preparation of the root was reported to have been used by Native Americans as a treatment for sore eyes. Preparations were also made to treat rheumatism, bronchitis, and snakebites, as well as to induce sterility.

Pelargonium is a genus of flowering plants which includes about 200 species of perennial, succulent, and shrub plants, commonly known as geraniums. Lemon geranium is commonly used as an astringent.

The present inventors have surprisingly found that a composition comprising extracts of at least three of Petroselinum, Cymbopogon, Citrus, Apium graveolens, Aloysia, Foeniculum, Melissa, Fortunella, Arisaema, and Pelargonium is highly effective in the treatment or prevention of cancer.

The composition was tested both in vitro and in vivo on a wide range of cancer types, with highly effective results.

In vitro studies were carried out at dilutions in the range of from about 1:50 to about 1:40,000, in cell medium, such as Dulbecco's Modified Eagle Medium.

According to some embodiments, the composition comprises extracts of Petroselinum, Citrus, and Cymbopogon.

According to some embodiments, the composition comprises extracts of Apium graveolens, Citrus, and Aloysia.

According to some embodiments, the composition comprises extracts of

Foeniculum, Citrus, and Melissa.

According to some embodiments, the composition comprises extracts of Arisaema, Fortunella, and Pelargonium.

Petroselinum may optionally comprise either Petroselinum crispum or Petroselinum neapolitanum.

According to some embodiments, Citrus is at least one of Citrus aurantifolia (key lime), Citrus medica (citron), Citrus reticulata (mandarin), Citrus aurantium (bitter orange), Citrus latifolia (Persian lime), Citrus limon (lemon), Citrus limonia (rangpur), Citrus paradisi (grapefruit), Citrus sinensis (sweet orange), Citrus tangelo (tangelo), Citrus nobilis (tangor), Citrus Clementina (clementine), Citrus reshni (Cleopatra mandarin), Citrus unshiu (satsuma), Citrus limetta (sweet lemon), Citrus limettiodes (sweet lime), Citrus latifolia (Persian lime), Citrus jambhiri (rough lemon), Citrus depressa (Hirami lemon), Citrus sudachi (sudachi), and Citrus volkameriana (volkamer lemon).

According to some embodiments, Cymbopogon is at least one of Cymbopogon ambiguus (Australian lemon-scented grass), Cymbopogon bombycinus (silky oilgrass), Cymbopogon citratus (lemongrass), Cymbopogon citriodora (West Indian lemongrass), Cymbopogon flexuosus (East Indian lemongrass), Cymbopogon martinii (palmarosa), Cymbopogon nardus (citronella grass), Cymbopogon obtectus (silky-heads), Cymbopogon procerus, Cymbopogon proximus, Cymbopogon refractus (barbed wire grass), Cymbopogon schoenanthus (camel grass), and Cymbopogon winterianus.

Optionally and preferably, the Cymbopogon comprises Cymbopogon citratus.

According to some embodiments, Aloysia comprises at least one of Aloysia triphylla, Aloysia dodsoniorum, Aloysia gratissima, Aloysia macrostachya, and Aloysia wrightii.

Optionally and preferably, the Aloysia comprises Aloysia triphylla (lemon verbena).

According to some embodiments, Melissa comprises at least one of Melissa axillaris, Melissa bicornis, Melissa flava, Melissa officinalis, and Melissa yunnanensis.

Optionally and preferably, Melissa comprises Melissa officinalis (lemon balm).

According to some embodiments, Fortunella (kumquat) comprises at least one of Fortunella margarita, Fortunella crassifolia, Fortunella hindsii, Fortunella japonica, Fortunella obovata, and Fortunella polyandra.

According to some embodiments, Arisaema comprises at least one of Arisaema amurense, Arisaema angustatum, Arisaema candidissimum, Arisaema concinnum, Arisaema consanguineum, Arisaema costatum, Arisaema dracontium, Arisaema elephas, Arisaema erubescens, Arisaema fimbriatum, Arisaema flavum, Arisaema grijfithii, Arisaema jacquemontii, Arisaema kiushianum, Arisaema lidaense, Arisaema lihenganum, Arisaema monophyllum, Arisaema nepenthoides, Arisaema peninsulae, Arisaema propinquum, Arisaema ringens, Arisaema robustum, Arisaema serratum, Arisaema sikokianum, Arisaema speciosum, Arisaema thunbergii, Arisaema tortuosum, Arisaema triphyllum, Arisaema undulatifolium, Arisaema undulatifolium, Arisaema thunbergii, Arisaema utile, Arisaema wattii, and Arisaema yamatense.

Optionally and preferably, Arisaema comprises Arisaema triphyllum.

Without wishing to be limited to a single hypothesis, it is believed that the combinations of natural extracts provide all of the following components which are responsible for the surprisingly effective anti-cancer effect: a combination of terpene aldehydes, (particularly citral, neral, linalyl adehyde, and others of similar classes), vitamin A, vitamin C, iron, vitamin Bl, isopropenyltoluene, hesperidin, limonene, elmene, copanene, b-sesquiphellandrene, and carotene.

For example, a composition according to the present invention may comprise at least one phenol (such as myristicin, eugenol, methyl eugenol, apiole, thymol, carvacrol, methyl chavicole, anethole, or safrole, or combinations thereof); at least one terpene (such as limonene, geraniol, pinene, camphene, cadinene, caryophyllene, cedrene, dipentene, phellandrene, terpinene, sabinene, myrcene, thujene or combinations thereof); at least one flavenoid (such as apigenin, crisoeriol, luteolin, apiin, tangeritin, chrysin, 6-hydroxyflavone, baicalein, scutellarein, or wogonin); and at least one vitamin such as a B vitamin (including folic acid, vitamin B9), vitamin A (for example, in the form of beta-carotene), and Pyrroloquinoline quinone.

According to some embodiments, the at least one phenol comprises myristicin, eugenol, and apiole.

According to some embodiments, the at least one terpene comprises beta phellandrene, limonene and alpha-thujene.

Preferably, the at least one flavonoid comprises crisoeriol, apigenin, apiin and leuteolin.

Embodiments of the present invention may therefore comprise, for example, myristicin, apiole, beta phellandrene, limonene, eugenol, alpha-thujene, crisoeriol, apigenin, apiin, leuteolin, beta carotene, folic acid, B vitamins, and Pyrroloquinoline quinone.

Before explaining at least one embodiment of the invention in detail, it is to be understood that the invention is not limited in its application to the details set forth in the following description or exemplified by the Examples. The invention is capable of other embodiments or of being practiced or carried out in various ways. Also, it is to be understood that the phraseology and terminology employed herein is for the purpose of description and should not be regarded as limiting. As used herein the term "about" refers to ± 10 %.

According to a preferred embodiment, the composition comprises extracts of Petroselinum crispum (parsley), Citrus reticulata (mandarin) and Cymbopogon citratus (lemongrass).

Optionally and preferably, the extract of Petroselinum crispum is obtained from the root of the plant, more preferably by alcohol extraction.

The extract of parsley root preferably has a concentration in the range of from about 20% to about 60% of the total composition, more preferably about 40%.

Optionally and preferably, the extract of Citrus reticulata is obtained from the peel of the fruit, more preferably by alcohol extraction.

The extract of mandarin peel preferably has a concentration in the range of form about 10% to about 30% of the total composition, more preferably about 20%.

Optionally and preferably, the extract of lemongrass comprises an essential oil obtained by steam distillation.

The lemongrass oil preferably has a concentration in the range of from about 20% to about 60% of the total composition, more preferably about 40%.

According to a preferred embodiment, the composition comprises about 40% extract of Petroselinum crispum root; about 20% extract of mandarin peel; and about 40% lemongrass oil. In some embodiments, such a composition is administered at a dilution of at least about 1:10, such as, for example, 1:20, 1:50, 1:100, 1:200, 1:400,

1:600, 1:800, 1:1600, 1:3200, and even at dilutions of greater than 1:3200.

According to a preferred embodiment, the composition comprises Apium graveolens (celery), Citrus aurantium or Citrus sinensis (bitter orange or sweet orange), and Aloysia triphylla (lemon verbena).

Optionally and preferably, the extract of Apium graveolens is obtained from the root of the plant, more preferably by alcohol extraction.

Optionally and preferably, the extract of orange is obtained from the peel of the fruit, more preferably by alcohol extraction.

Optionally and preferably, the extract of lemon verbena comprises an essential oil obtained by steam distillation.

According to a preferred embodiment, the composition comprises Foeniculum vulgare (fennel), Citrus Union (lemon), and Melissa officinalis (lemon balm).

Optionally and preferably, the extract of fennel is obtained from the root of the plant, more preferably by alcohol extraction.

Optionally and preferably, the extract of lemon is obtained from the peel of the fruit, more preferably by alcohol extraction.

Optionally and preferably, the extract of lemon balm comprises an essential oil obtained by steam distillation.

According to a preferred embodiment, the composition comprises Arisaema triphyllum (Jack-in-the-pulpit), Fortunella (kumquat) and Pelargonium crispum (lemon geranium).

Optionally and preferably, the extract of Arisaema triphyllum is obtained from the root of the plant, more preferably by alcohol extraction.

Optionally and preferably, the extract of kumquat is obtained from the peel of the fruit, more preferably by alcohol extraction.

Optionally and preferably, the extract of lemon geranium comprises an essential oil obtained by steam distillation.

The composition of the present invention is useful for treatment of a wide range of cancer types.

According to some embodiments, the cancer which is treatable by the composition of the present invention comprises at least one of leukemia, lung cancer, liver cancer, breast cancer, colon cancer, glioma, and pancreatic cancer.

According to some embodiments, there is provided a method of treating cancer, the method comprising administering to a patient in need thereof a composition comprising extracts of at least three of Petroselinum, Cymbopogon, Citrus, Apium graveolens, Aloysia, Foeniculum, Melissa, Fortunella, Arisaema, and Pelargonium.

According to some embodiments, the composition or method of the present invention may optionally further comprise one or more additional ingredients, such as, for example, a chemotherapeutic agent.

Examples of suitable chemotherapeutic agents include, without limitation, alkylating agents, anti-metabolites, plant alkaloids and terpenoids, vinca alkaloids, podophyllotoxin, taxanes, and topoisomerase inhibitors.

According to some embodiments, an additional active ingredient may be coadministered either with the composition of the present invention, either as a single dosage form or in separate dosage forms, either concurrently or sequentially, wherein the additional active ingredient is administered either before or after the composition of the present invention.

Suitable routes of administration may, for example, include oral, rectal, transmucosal, especially transnasal, intestinal, or parenteral delivery, including intramuscular, subcutaneous, and intramedullary injections, as well as intrathecal, direct intraventricular, intravenous, inrtaperitoneal, intranasal, or intraocular injections.

Alternately, one may administer the pharmaceutical composition in a local rather than systemic manner, for example, via injection of the pharmaceutical composition directly into a tissue region of a patient.

Preferably, the composition of the present invention is administered orally. Pharmaceutical compositions of the present invention may be manufactured by processes well known in the art, e.g., by means of conventional mixing, dissolving, granulating, dragee-making, levigating, emulsifying, encapsulating, entrapping, or lyophilizing processes.

Pharmaceutical compositions for use in accordance with the present invention thus may be formulated in conventional manner using one or more physiologically acceptable carriers comprising excipients and auxiliaries, which facilitate processing of the active ingredients into preparations that can be used pharmaceutically. Proper formulation is dependent upon the route of administration chosen.

For oral administration, the pharmaceutical composition can be formulated readily by combining the active compounds with pharmaceutically acceptable carriers well known in the art. Such carriers enable the pharmaceutical composition to be formulated as tablets, pills, dragees, capsules, liquids, gels, syrups, slurries, suspensions, and the like, for oral ingestion by a patient. Pharmacological preparations for oral use can be made using a solid excipient, optionally grinding the resulting mixture, and processing the mixture of granules, after adding suitable auxiliaries as desired, to obtain tablets or dragee cores. Suitable excipients are, in particular, fillers such as sugars, including lactose, sucrose, mannitol, or sorbitol; cellulose preparations such as, for example, maize starch, wheat starch, rice starch, potato starch, gelatin, gum tragacanth, methyl cellulose, hydroxypropylmethyl-cellulose, and sodium carbomethylcellulose; and/or physiologically acceptable polymers such as polyvinylpyrrolidone (PVP). If desired, disintegrating agents, such as cross-linked polyvinyl pyrrolidone, agar, or alginic acid or a salt thereof, such as sodium alginate, may be added.

Preferably, the composition is administered in the form of a liquid.

Pharmaceutical compositions suitable for use in the context of the present invention include compositions wherein the active ingredient is contained in an amount effective to achieve the intended purpose. More specifically, a

"therapeutically effective amount" means an amount of active ingredient effective to prevent, alleviate, or ameliorate symptoms of cancer.

Determination of a therapeutically effective amount is well within the capability of those skilled in the art, especially in light of the detailed disclosure provided herein.

For any preparation used in the methods of the invention, the dosage or the therapeutically effective amount can be estimated initially from in vitro and cell culture assays. For example, a dose can be formulated in animal models to achieve a desired concentration or titer. Such information can be used to more accurately determine useful doses in humans.

Toxicity and therapeutic efficacy of the active ingredients described herein can be determined by standard pharmaceutical procedures in vitro, in cell cultures or experimental animals. The data obtained from these in vitro and cell culture assays and animal studies can be used in formulating a range of dosage for use in human. The dosage may vary depending upon the dosage form employed and the route of administration utilized. The exact formulation, route of administration, and dosage can be chosen by the individual physician in view of the patient's condition. (See, e.g., Fingl, E. et al. (1975), "The Pharmacological Basis of Therapeutics," Ch. 1, p.l.)

Dosage amount and administration intervals may be adjusted individually to provide sufficient plasma or brain levels of the active ingredient to induce or suppress the biological effect (i.e., minimally effective concentration, MEC). The MEC will vary for each preparation, but can be estimated from in vitro data. Dosages necessary to achieve the MEC will depend on individual characteristics and route of administration. Detection assays can be used to determine plasma concentrations.

Depending on the severity and responsiveness of the condition to be treated, dosing can be of a single or a plurality of administrations, with course of treatment lasting from several days to several weeks, or until cure is effected or diminution of the disease state is achieved.

The amount of a composition to be administered will, of course, be dependent on the subject being treated, the severity of the affliction, the manner of administration, the judgment of the prescribing physician, etc. Compositions of the present invention may, if desired, be presented in a pack or dispenser device, such as an FDA-approved kit, which may contain one or more unit dosage forms containing the active ingredient. The pack may, for example, comprise metal or plastic foil, such as a blister pack. The pack or dispenser device may be accompanied by instructions for administration. The pack or dispenser device may also be accompanied by a notice in a form prescribed by a governmental agency regulating the manufacture, use, or sale of pharmaceuticals, which notice is reflective of approval by the agency of the form of the compositions for human or veterinary administration. Such notice, for example, may include labeling approved by the U.S. Food and Drug Administration for prescription drugs or of an approved product insert. Compositions comprising a preparation of the invention formulated in a pharmaceutically acceptable carrier may also be prepared, placed in an appropriate container, and labeled for treatment of an indicated condition, as further detailed above.

Additional objects, advantages, and novel features of the present invention will become apparent to one ordinarily skilled in the art upon examination of the following examples, which are not intended to be limiting. Additionally, each of the various embodiments and aspects of the present invention as delineated hereinabove and as claimed in the claims section below finds experimental support in the following examples.

EXAMPLES Example 1: Representative composition Extract of Petroselinum crispum root: 40%

Extract of mandarin peel: 20% Lemongrass oil: 40%

The Petroselinum crispum and mandarin peel extracts were prepared by steam distillation. The lemongrass oil was prepared by steam distillation. Specifically, the plant material was placed in a glass vessel together with one volume distilled water and one volume ethanol (95%) and heated until reflux at 80° C. The steam was condensed to yield the respective extract.

Example 2: Effect of the composition on treatment of cancer in human patients The composition of Example 1 was administered to five patients, two of whom were suffering from chronic myelogenous leukemia, one from pancreatic cancer, one from ceracoma and one from acute myelogenous leukemia.

The composition was administered orally on a daily basis, as a food supplement in honey, at dilution of 1:200. Blood counts were taken at the time of administration, and at the intervals detailed in Table 1 below, for a total period of about 5 months. Representative results from a single CML patient are shown in Table 1. Treatment with the composition of

Example 1 (LPC) began on 12-08-08.

As seen in the Table, white blood cell (WBC) levels were brought within the normal range following administration of the test composition, and the overall blood profile was generally improved.

Table 1 : Representative results from a single CML

Table 1 Continued

VO


Example 3: Effect of the composition on human cancer cell lines in vivo (MTT asssay)

The following human cell lines, obtained from Hadassah Ein Kerem, Jerusalem, were tested: DU145 (prostate cancer) H358 (lung cancer) SNB- 19 (giloma) Panc-1 (pancreatic cancer) HT-29 (intestinal cancer) Compositions A, B, and C were tested on each of the above cell lines, wherein composition A is the composition of Example 1, with mandarin peel extract diluted to 90% of the original concentration in RPMI; composition B is the composition of Example 1, with mandarin peel extract diluted to 80% of the original concentration; and composition A is the composition of Example 1, with mandarin peel extract diluted to 70% of the original concentration.

The MTT assay was carried out as known in the art. Briefly, cells (104-106) were plated in 200 μl PBS in 96-well plates and incubated prior to testing. 20 μl of MTT solution was added and mixed by shaking. Plates were incubated for 4 hours at 370C in dark, during which time living cells convert the tetrazolium component of the MTT solution into a formazan product. Solubilization solution was then added to the wells to stop the reaction and solubilize the formazan crystals. Plates were read in ELISA Reader at 570 nm. For each test composition, the highest effective dilution was identified i.e. that at which over 50% inhibition was shown in the MTT test. Results are shown in Table 2.


Table 2

As shown in Table 2, all compositions tested were shown to be effective in the MTT test, at dilutions in RPMI in the range of at least 1 :400, and up to 1 :800. For the HT-29 and glioma cell lines, compositions were shown to be effective at dilutions of up to about 1:1600, and even greater than 1:3200.

Example 4: In vivo animal studies A. Toxicity studies

Male Siberian nude mice, aged 2 months, were injected intraperitoneally with 0.5 ml of the composition according to Example 1, at dilutions of 1:10, 1:200 and 1:400 in RPMI medium. Each dilution was administered to 7 mice. All animals survived with no side effects. An additional 7 mice were injected ip with undiluted composition. Animals which received undiluted composition ceased to move within 30-60 hours, and 6 of the 7 died within 3 days of injection.

In a repeat experiment, using 1:10 dilution and undiluted composition, all animals receiving the diluted composition survived, while 2 out of 7 which received the undiluted composition survived. The effect of solvent, comprising the extract of Petroselinum crispum root, prepared according to Example 1, was studied on two further groups of 7 mice each. A first group received 0.5 ml of solvent, diluted 1:10 in RPMI medium. A second group received undiluted solvent. All mice receiving the diluted solvent survived; two out of seven mice receiving the undiluted solvent survived.

B. Anti-tumor effect

Two groups of male nude mice were studied. All mice received subcutaneous injection of 0.1 ml of a suspension comprising 0.5 x 106 HT-29 cells (a cell line derived from human intestinal cancer and grown in vitro). The composition of Example 1 was administered to a first group (8 mice) and solvent alone (i.e extract of Petroselinum crispum root) was administered to a second group (7 mice). Administration comprised 3 injections per week, for a period of 5 weeks. Each injection comprised 0.5 cc of composition/solvent, at a dilution of 1:10, beginning 2 days after subcutaneous injection of the cells. Tumor size was examined at day 2 after subcutaneous xenograft of HT-29 cells, again at day 9, and then once per week for 6 weeks. Tumors were detectable from week 3. Table 3 below shows average tumor size in cm for mice which received the test composition of Example 1, and those which received solvent alone. As seen in the Table, by week 5 of administration, tumor size had significantly decreased in the group which received the test composition, but not in the group which received solvent alone.

Table 3

Example 5: PET-CT studies

Positron emission tomography - computed tomography (PET-CT) was used for imaging of metastatic cancer of the liver and lungs in a patient suffering from intestinal cancer. The study was conducted by Prof. Haim Tarsa at the CT- Institute of Ramat Aviv Medical Center, Israel.

The patient had previously undergone partial liver resection and radiofrequency (RF) therapy. At the time of the present evaluation, the patient was receiving treatment with the composition of Example 1 alone.

Prior to treatment, cancerous growths were shown to be present in the liver, intestine and lungs. After 5 months treatment with the composition of Example 1, the growths in the liver and intestine were no longer detectable, while the growth in the lungs had significantly decreased in size.

Although the invention has been described in conjunction with specific embodiments thereof, it is evident that many alternatives, modifications and variations will be apparent to those skilled in the art. Accordingly, it is intended to embrace all such alternatives, modifications and variations that fall within the spirit and broad scope of the appended claims.

All publications, patents and patent applications mentioned in this specification are herein incorporated in their entirety by reference into the specification, to the same extent as if each individual publication, patent or patent application was specifically and individually indicated to be incorporated herein by reference. In addition, citation or identification of any reference in this application shall not be construed as an admission that such reference is available as prior art to the present invention.