WO2005030237A1

WO2005030237A1 - A pharmaceutical composition comprising catharanthus roseaus, (vinca rosea), its preparation and use thereof

Info

Publication number: WO2005030237A1
Application number: PCT/PH2004/000003
Authority: WO
Inventors: Consuelo Macalintal-Azores, Md.
Original assignee: Señor Rafael Phil. Inc.
Priority date: 2003-09-26
Filing date: 2004-03-30
Publication date: 2005-04-07

Abstract

The invention relates to a pharmaceutical composition comprising Catharanthus Roseaus (Vinca Rosea), preferably its leaves thereof, its process of preparation and its use thereof as anticancer.

Description

A Pharmaceutical Composition Comprising Catharanthus Roseaus, (Ninca Rosea), Its Preparation and Use Thereof

Technical Field

The invention relates to a pharmaceutical composition comprising Catharanthus Roseaus (Ninca Rosea), preferably its leaves thereof, its process of preparation and use thereof as anticancer.

Background Art

Cancer as a disease ranks first in the International Statistical Classification of Diseases. It rank 4^th in 10 leading causes of death in the Philippines, with an increasing trend.

Options for treating cancer such as surgery, chemotherapy, and radiation require substantial amounts of money thus financially draining. These procedures produce side effects that also limit normal function of the individual and worst, when cancer is at its last stage, where surgery, chemotherapy and radiation therapy are not options anymore, patients lie bedridden and progressively debilitated until they succumb to death.

The invention is intended to help the terminally ill patients with cancer specially those who refuse chemotherapy, surgery and radiation, those who accept chemotherapy but refused surgery or vice versa and those given a short period of survival by their physician, who for financial reason prefer taking herbal agent that is naturally prepared. The invention can be taken orally.

The dimeric alkaloids extracted from aerial part of Catharanthus Roseaus are manifested as lyophilisate designed for intravenous route. Vindesine and vinorelbine are semi-synthesized derivative of vinblastine marketed as sulfate and bitartrate for infection solution, so expensive that only few can afford. Catharanthus Roseaus average 2 feet long in height with glossy dark leaves with more or less 2 inches in length with white flowers at its branching stems. It is popularly used as ornamental plant and grows in perennial tropical regions.

White flowered Catharanthus Roseaus contains .2 to 1% alkaloids with its anticancer activity such as vincristine in small amount, e.g. in small amount, up to 3g/ of dried prepared leaves and vinblastine in slightly higher amount. The rose purple flowered Catharanthus Roseaus has a higher yields while the white red eyed flower has the highest yield (PROSEA vol. 12 (1) Med. & Poisonous Plant 185-190).

Vinblastine and vincristine have the following structural formulas:

VLNBLASTΓNE (R= CH₃) VΓNCRISTΓNE (R = CHO) Vincristine and vinblastine in alkaloids of Catharanthus Roseaus are known cytospecific and phase specific, blocking mitosis in stage resulting in dysfunction of mitotic spindle apparatus, freeze the metaphase stage and prevent cell proliferation (Lipincott Pharma Mary Mycek et. al.).

Therefore, the present invention provides an option which may be effective in at least providing comfort, if not complete cure to patients with cancer making their remaining days fruitful, less dependent and even to prepare acceptance, of inevitable, end of their life.

Brief Description of the Drawings

Figure 1 is an illustrative drawing of the flowering twig, fruit, leaf and seed of a white flowered Catharanthus Roseaus. Figure 2 is an illustrative drawing of normal mitosis. Figure 3 is an illustrative drawing of mitosis blocked by vinca alkaloids.

Detailed Description

The invention relates to a pharmaceutical composition comprising Catharanthus Roseaus, preferably its leaves thereof, its process of preparation and use thereof as anticancer. The invention provides for a pharmaceutical composition comprising leaves of Catharanthus Roseaus.

It also provides for a pharmaceutical composition comprising leaves of Catharanthus Roseaus, wherein the Catharanthus Roseaus is a white flowered Catharanthus Roseaus.

It also provides for the use of the Catharanthus Roseaus, more preferably its leaves thereof for the preparation of a medicament for the treatment of cancer. It also provides a method of treatment of cancer by administering the effective amount Catharanthus Roseaus to a patient in need thereof.

It further provides for a pharmaceutical composition of the present invention in the form of powder, tablets or capsules.

In the present specification, the term Vinca refers to Catharanthus Roseaus (Vinca Roseaus). The process for preparing the pharmaceutical composition of the present invention comprises the following steps: a) choosing healthy leaves of Catharanthus Roseaus b) washing and cleaning each chosen leaf c) separating the leaves from the stem d) dehydrating the separated leaves e) placing the dehydrated leaves in a container to avoid chemical reaction f) covering the container with thin cloth to prevent the dehydrated leaves ffom contamination g) exposing the leaves in the covered container to controlled temperature, for the leaves to dry and to become crunchy h) converting the crunchy leaves into powdered form i) placing the powdered leaves in a tightly covered container with collection and preparation data label. j) measuring and preparing the powdered leaves into tablet or capsule form by using calibrated weighting scale, for safe effective dose.

The dose was computed according to body surface area using nomogram.

Illustrative Example:

The leaves of white-flowered Catharanthus Roseaus were carefully chosen and identified. Bunchy plants infected with mycoplasma-like organism such as those with small leaves and stunted flowers with yellow foliage were excluded, so those with damaged leaves and leaves with insect bites. After thorough washings and cleanings of each leaf of white flowered Catharanthus Roseaus, the leaves were separated from the stems and were dehydrated. The leaves were placed in prescribed containers to avoid chemical reaction, covered with thin cloth to prevent from contamination and exposed to controlled temperature to dry. When the leaves became crunchy, it was then converted into powdered form, placed in a tightly covered container with collection and preparation data. Calibrated weighing scale were used for safe effective dose, powdered leaves were measured and prepared in capsule form. Dose computed according to body surface area using nomogram.

Clinical Test Results

Patents were given capsule prepared according to the illustrative example, hereinto referred as Vinca capsule, and were followed-up for improvement and side effects if any on the 3^rd - 4^th day after, and after one month.

Blood examination, x-ray/ultrasound if possible was part of the requirements for each case. They were also required to sign the consent.

Example 1

A 48-year old woman was diagnosed with colonic cancer voluntarily consented to take the naturally prepared Vinca capsules after refusal to any surgical intervention/chemotherapy. Her mother and a sister died of the same illness after such procedures. She was non-ambulatory markedly pale with anasarca and several masses palpated over the lower abdomen, when first seen. She improved markedly after intake of the naturally prepared Vinca capsules, went back to her catering job weeks after, comfortable and with functioning life. Example II

A 57-year-old woman patient diagnosed as ovarian cancer stage IV with metastasis over the uterus, cervix and supraclavicular lymph node was operated but developed anasarca pleurisy with effusion 4 months after operation. There was bilateral ureteral obstructive uropathy. Hemodialysis was done 2 times and ureteral catheter was inserted. The patient was sent home given 10 days of survival. She improved markedly 2 weeks after taking the naturally prepared Vinca capsules of the present invention, lived comfortably, no edema, no pain and no dyspnea.

Example III

A 65-year-old man was diagnosed to have metastasis brain tumor from lung cancer. Due to financial constraint opted not to undergo biopsy, chemo and radiation therapy. Prior to giving the naturally prepared Vinca capsules 2 x times a day he was just bedridden with spontaneous eye opening but no eye contact. He does not follow command, nor respond to any stimulation. After 10 days receiving the Vinca capsules, without other medications, he started to respond to relative's instruction by nodding with facial expressions and with very good eye contact. He also started to gain weight.

Example IN

A 32-year old man patient consulted for severe headache, blurring of vision, impaired hearing of left ear, and swollen face of week's duration. On examination, the patient walked with support, incoherent, irritable, dysphasic, swollen face, left eye protrusion, (-) eye contact, motor, no coordination of lower extremities. He consulted a physician in USA who diagnosed him to be a case of brain malignancy six months prior to consultation. Radiation was done only once as he decided to come home for treatment. Three months prior the consultation, he was brought to University of Santo Tomas Hospital (UST) for on and off seizures, headache, dizziness and altered sensorium. MRI revealed large heterogeneous mass in the left fronto-parietal region with peripheral edema, crosses the Genu Corpus Callosum and with areas of hypomtense signal representing necrosis. There was a shift of midline structures to the right, compression of left lateral ventricle and with associated dilatation of the body and occipital horn of right lateral ventricle. Impression then was GLEOBLATASMA MULTIFORME with non- communicating Hydrocephalus. Tube was inserted. Chemotherapy and radiation were done but to no avail. On the day of consultation, he was given Vinca capsule of 2 mg 3 times a day. On his first week of treatment, an improvement was noticed and the treatment was continued. After 3 weeks of treatment with the Vinca capsules, he experienced a marked improvement. Eye protrusion was almost gone and he already had eye contact (-) seizures, less headache and could already walked with little support from relative. The treatment was continued for another week. After less than a month and a half, he walked without support. He was cooperative and was complaining only of slight blurring vision. Eye protrusion (-). He was advised to continue the treatment at a reduced dose of 2 times daily for 2 weeks then discontinue for at least weeks before resuming for another session treatment of 6-

8 weeks cycle of 15 cycles. Performance scale from 30 to 80% (Karnofsky) After a succeeding month, repeat MRI showed significant reduction in size of the cystic necrotic tumor in the left frontal lobe with extension to Corpus Callosum, from 6.5 x 7.5 x 6 cm to 4.5 x 5x 4.3 cm with obvious reduction of vasogenic edema, mass effect and midline shift. Ventricles are not dilated as before. No new lesion was noted.

Example 5

A 19 -year old male, complained of an on and off headache of almost 5 years duration accompanied by an episode of seizure. He was brought to UST Hospital and was diagnosed to have Glioblastoma grade II. He was given steroids as Decilone Fte and Tapamaze 50 mg daily. His headache over the vertex and frontal areas became frequent and a private neurologist was consulted. There was no accompanying numbness, weakness and diminishing vision. He complained also of cough with yellowish phlegm and marked weight loss. Cranial MRI was done and showed 1.0 x 1.0 x 1.9 cm tumoral mass in the root of fourth ventricle with extension into Sylvian aqueduct, with mild heterogeneous enhancement after GD-DTPA injection. 3^r and 4^th ventricles are dilated with more prominence of the left lateral ventricle. Craniostomy was done. Oxycarbamazine 300 mg was prescribed. Three months after he had a frequent headache, he developed persistent headache and result to taking decoction of Vinca for 2 weeks, and then change to Vinca capsule 2 mg 3 times daily for 1 month. It was then reduced to 2 times daily as improvement was felt. After five months, CT Scan was repeated and revealed significant decrease in ventricular dilatation compared to CT scan done when his headache was frequent. Previously noted ventricular mass primarily at the 4^th ventricle not appreciated anymore. Performance scale after 5 months, form 40 to 90% (Karnofsky) After a succeeding month, he resume work. He was advised to continue Vinca capsules as instructed.

Decoctions from leaves of Catharanthus Roseaus are so slimy and not acceptable to patients for its smell and taste.

While the invention has been described with respect to the above embodiments, it should be recognized that various modifications and changes may be made to the invention by those skilled in the art which also fall within the scope of the invention as defined by the appended claims.

Claims

Claims:

1. A pharmaceutical composition comprising leaves of Catharanthus Roseaus.

2. A pharmaceutical composition according to claim 1 , wherein the Catharanthus Roseaus is a white flowered Catharanthus Roseaus.

3. A pharmaceutical composition according to claim 1 or 2 for use in the treatment of cancer.

4. A pharmaceutical composition according to claim 3 in the form of powder, tablets or capsules.

5. Use of Catharanthus Roseaus more preferably its leaves thereof in the preparation of medicament for the treatment of cancer.