AU700682B3

AU700682B3 - Composition and method of treatment

Info

Publication number: AU700682B3
Application number: AU60723/98A
Authority: AU
Inventors: Stella Levinsky; Albert Dr. Shafransky; Leonid Shafransky
Original assignee: Individual
Current assignee: Ilsa Super Pty Ltd
Priority date: 1997-04-14
Filing date: 1998-04-09
Publication date: 1999-01-14
Anticipated expiration: 2004-04-09

Description

PATENT SPECIFICATION

AUSTRALIA

*oo Leonid Shafransky Albert Shafransky Stella Levinsky @0 0000 *00 *06 0 Setmbr19 Calcium phosphate monobasic composition and its use in methods of treatment Abstract Current Patent is related to medicine and the purpose if this Patent is to facilitate a wide implementation into medical practice of calcium phosphate monobasic for treatment of wide range of diseases and conditions including, but not limited to: disturbance or reparative regeneration of the skin and bones, falling hair and disturbance of nail growth, calf muscle cramps, decreased appetite, constipation, wrinkles, slow or absent consolidation of traumatic and pathological fractures, postlactative osteoporosis and bone defects, age osteoporosis and postmenopausal osteoporosis, complicated bone fractures, adynamia of different origins; muscular dystrophy and sexual disturbances, dermatological conditions such as psoriasis, eczematous defects after burns including sunburns, decreased turgor of the skin.

This Patent also recommends using calcium phosphate monobasic for calcification of necrotic tissues are those applicable to all types of malignancy both during and after all types S 15 of treatment including radiotherapy and chemotherapy.

3 claims Technical Field The present invention relates to calcium containing pharmaceutical compositions and methods of treatment using those compositions. In particular, it relates to treatment of a range of medical illnesses including dermatological conditions, cancer and bone fractures with calcium phosphate monobasic.

Background Art There are variety of calcium medications available in medicine. However, calcium phosphate monobasic Ca(H 2

PO

4 2 has not been used in the form of medication for application to human (even though it is known to be used in veterinary science for increasing muscular mass and improving quality of milk in animals). It is also used in the baking industry for bread fermentation, and in analytical chemistry as a reagent.

I"X Disclosure of the Invention According to the first form of this invention there is provided a composition containing calcium phosphate monobasic together with a pharmaceutically acceptable carrier, diluent and/or excipient.

In the second form of this invention it is provided a method for treatment of pathological conditions by improving reparative regeneration of normal tissues or calcification of necrotic tissues in patients, by administering an effective amount of calcium phosphate monobasic to the patients. Examples of conditions to which the compositions and methods of this invention applicable are disturbance or reparative regeneration of the skin and bones, 10 falling hair and disturbance of nail growth, calf muscle cramps, decreased appetite, constipation, wrinkles, slow or absent consolidation of traumatic and pathological fractures, postlactative osteoporosis and bone defects, age osteoporosis and postmenopausal osteoporosis, complicated bone fractures, adynamia of different origins; muscular dystrophy and sexual disturbances, dermatological conditions such as psoriasis, eczematous defects after *o S 15 burns including sunburns, decreased turgor of the skin. Examples of methods in accordance with the invention for calcification of necrotic tissues are those applicable to all types of malignancy both during and after all types of treatment including radiotherapy and o chemotherapy.

In the method of the intention, calcium phosphate monobasic may be administered by itself or in a pharmaceutical composition, which comprises that compound and a suitable carrier, diluent, excipient and/or adjuvant, examples of which are well known to those skilled in this art.

Usually, the calcium phosphate monobasic is mixed with a fatty substance which minimises irritation of the stomach mucosa (since calcium phosphate monobasic is acidic) when the mixture is ingested. This combination also ideally potentiates bile function in the absorption of calcium phosphate monobasic in the small bowel. A suitable fatty substance is butter. Margarine or a sour cream or other similar fatty substances such as lard or vegetable oil can also be used in the place of butter. Typically, ingestion of calcium phosphate monobasic and this fatty substance is followed by ingestion of a quantity of fluid such as V, o water, fruit juice or fruit cordial. Preferable, fruit juice is used since this aids the ingestion and absorption of calcium phosphate monobasic by increasing acidity in the small bowel.

The therapeutic dosage range of calcium phosphate monobasic is about 30g to about 200g per course of treatment. The course can be repeated in approximately one month. The calcium phosphate monobasic may be given at various times during the day, typically 2-8 times per day, more typically three times per day. A suitable dosage may be between 3g to 6g per day spread over 3 instances of administration. As a guide, the amount of compound administered is typically about 30 to 50mg/kg/dose. Usually, the calcium phosphate :monobasic is administered in lg amounts. A total therapeutic amount for a course of S: 10 treatment is typically 30g to 200g, more typically about 100g. Each of these courses may be repeated after a certain period of time, suitably in about 1 to 2 months. The effect of treatment may become apparent in 3 to 5 days.

The amount of fatty substance mixed with the calcium phosphate monobasic is an amount sufficient to aid the ingestion of that compound, for example from about 0.5g to or more, and is typically about 1 to 2g.

Calcium phosphate monobasic is usually administered as a powder. However, it may also be made into tablets, or be administered in the form of a syrup, or in capsules.

The present inventors have for the first time introduced calcium phosphate monobasic into oncology practice. It is theorised that this is the only calcium containing medication which is possible to introduce calcium ions into the tumor cells. The mechanism of action may be as follows. After being introduced to the cancer cell the compound provides additional amounts of calcium to the cell and downregulates metabolic functions of cancer cells, which causes malignant cells to die. (b)Cells that are not completely transformed into cancer cells return to their "normal state". The basis of the method of treatment of this invention may rest upon the combination of calcium and phosphate in calcium phosphate monobasic, compared to other known calcium-containing medications.

i •I i i u" s,/ Best Mode and Other Modes For Carrying Out The Invention An effective amount of calcium phosphate monobasic is administered orally and optionally is given together with butter, followed by a suitable amount of a drink such a fruit juice. For example, Ig of calcium phosphate monobasic is mixed with approximately one teaspoon of butter. This combination is given three times a day for 10 to 30 days.

Administration of this medication to oncological patients showed that it is also has a positive influence on different system in the human organism such as stimulation of reparative regeneration of the skin, hair and nail growth, consolidation of traumatic and pathological fractures, improvement of intestinal function.

The present invention will be described with reference to the following examples in comparison with control groups of patients who have not been given calcium phosphate monobasic and have not demostrated any changes. In relation to all study groups of patients there was no change in diet pattern or any other activites that could account for corresponding •changes apart from intake of calcium phosphate monobasic.

Clinical Finding.

Example 1 Activity 1: To study the activity of calcium phosphate monobasic in different tissues and organs, an experimental investigation in rats was carried out using radioactive techniques. An 20 aqueous solution of p32 labelled calcium phosphate monobasic was introduced orally to the ;rats. After certain periods of time, the animals were killed, and samples were prepared.

Amounts of phosphate in different tissues and organs was identified by measuring the bioactivity. This study showed that there was a significant difference in phosphate behavior in various tissues and organs.

The amount of phosphate in the gastrointestinal tract dropped rapidly and in 96 hours its activity was substantially lower than the initial activity. In the majority of organs, (heart, lungs, kidneys, spleen, liver) after reaching a maximum, the amount, of phosphate begins to Sdecrease in 168 hours. An exception was brain, which was characterised by more gradual 1' N deposition and longer decrease. Decrease of amount of phosphate in bones occurs at a significantly lower rate and in some circumstances does not occur at all skull bones Example 2 Influence of Calcium Phosphate Monobasic on Tumor Growth The influence of calcium phosphate monobasic on tumor growth has also been studied by administering 32.5 mg of calcium phosphate monobasic per kg of body weight three times daily for 33 days. For these studies, mongrel rats where used, to whom Plisse lymphosarcoma (radiosensitive type) was implanted. Tumour growth was halted in 50-60% of the rats.

Studies were also carried out on the combined effect of radiation therapy and calcium phosphate monobasic on implanted tumors. Tumor growth was halted in 75-98% of the rats subjected to the combined treatment.

Example 3 Use of the Medication of this Invention Calcium phosphate monobasic in powder form is dispatched in 1 g amounts, optionally 15 in water-proof paper. Patients take one such portion and pours it into a teaspoon containing a **piece of butter, about 1 to 2 g, and mix both substances. This mixture is then swallowed, followed by a drink of lemon juice or any other juice. This is repeated 3 times a day. A total therapeutic amount for a course of treatment is 100g. The courses can be repeated in 1-2 months. The effect of treatment often may become obvious in 3-5 days.

20 Example 4 Psoriasis 36 patients were treated with late psoriasis by administering Ig calcium phosphate 0. monobasic three times daily for 33 days. Distribution and localisation of psoriasis was different, as well as the thickness of the plaques as compared with control group In 2-3 weeks plagues disappeared in 80-85% of patients. The medication was used separately without any other medications and the diet was not modifed.

/ii Example Plastic Surgery of the Skin The medication was used after replacement of a skin lesion with a skin graft from another part of the body after plastic surgery of the skin) for example. It may be used on large skin wounds (on abdomen, on chest wall) after removal of late and previously treated skin cancer (including after radiotherapy). The dosage of calcium phosphate monobasic was lg three times daily for 33 days. In 3 to 4 weeks all the surface (200-300 cm 3 was covered by a newly formed skin, although skin transplants were dissolved in 7 to 10 days. In the rest of the time active reparative regeneration followed and the skin surface completely closed.

There were 15 patients in this study.

Example 6 Cancer of vulva In 10 patients treatment consisted of combination of radiotherapy of the tumour and calcium phosphate monobasic at a dosage of Ig three times daily for 33 days. It was observed 15 that the tumor shrunk following 2 to 3 weeks of treatment. Signs of calcifications in histopathological samples of the tumors were also noted.

Example 7 Long-standing Non-uniting Fractures Definite signs of consolidation appeared on X-rays of 12 patients one month after 20 intake of calcium phosphate monobasic at a dosage of Ig three times daily for 33 days.

Example 8 Eczematous Defects After Sun Burns In 3 patients, starting from day 5 and up to day 21, all defects on head and forearms completely repaired after taking calcium phosphate monobasic at a dosage of Ig three times daily for 33 days.

Example 9 Cosmetic Changes of the Skin of the Face and Body In this example, 50 patients were studied. These patients received a dosage of Ig i calcium phosphate monobasic three times daily for 33 days, it was found that particularly in women, turgor of the skin improved, there was a decrease in the number of wrinkles, decrease in hear loss and disappearance of calf muscles cramps.

Example Improvement in Function of Gastrointestinal System and Sexual Dysfunction In all observed patients who took calcium phosphate monobasic and suffered from constipation or irregular bowel motions, normalisation of bowel motions was noted. Patients noted improvement of appetite after 5-7 days after commencement of the course of treatment.

Improvement of sexual activity was also noted in elderly patients who took calcium phosphate monobasic for treatment of other conditions.

Example 11 Influence on bone density It was noted that those patients who were treated with administration of therapeutic amount of calcium phosphate monobasic for underlying conditions and who had concurrent osteoporosis demonstrated increase of the bone density on the X ray films.

i' S:i 15 Industrial Applicability The composition and methods of treatment of this invention will find wide use in the medical field. The foregoing describes only embodiments of the present invention and modifications obvious to those skilled in the art can be made thereto without departing from the scope of the invention.

o •on o *o

Claims

1. muscular dystrophy and sexual disturbances; mn, dernmatological conditions such as psoriasis, eczemnatous defects after burns including sainburns, decreased tturgor of the skin;, for calcification of necrotic tissues appi-cable to all types Of Mal'gac ohdrn n fe all types of treaftnent including radiotherapy and chemotherapy, .:comprising oral administration to a subject in. need of thereof calcium Phosphate monobasic i SAn: therapeutically effective amounits. The use as defined in Claim 1, wherein said calcium Phosphate monobasic isadmi nistered o* either by itself or in a pharmaceutical composition, and wherein said calcium -phosphate mbnobasic is administered with fatty substance sufficient to aid the ingestion of calcium phsPhate obsi from about to log or m~ore, and is typically about 1 to 2g, followed. by a fruit Juice, wvater or cordial 3, The se as efined n Cla. 1, wherein calcium phosphate monobasic, is adminstre i therapeutic amount 30 to 50mg/kgdose three times per day in a total daily amount between 3g to 6g, where the total amount of calcium phosphate monobasic is ranging froT 0 oaot20 e course of treatmnent, which. can be repeated in approximately one month- DATED

2 November 1998 Leonid Shafransky Albert Shafransky Stella Levinsky a a a. a a a a a. a