CA1142855A - Antitumoral composition and its process of preparation - Google Patents
Antitumoral composition and its process of preparationInfo
- Publication number
- CA1142855A CA1142855A CA000354516A CA354516A CA1142855A CA 1142855 A CA1142855 A CA 1142855A CA 000354516 A CA000354516 A CA 000354516A CA 354516 A CA354516 A CA 354516A CA 1142855 A CA1142855 A CA 1142855A
- Authority
- CA
- Canada
- Prior art keywords
- solution
- chlorhydrate
- ethanol
- amino
- boric acid
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/22—Boron compounds
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Inorganic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
Abstract
ABSTRACT OF THE DISCLOSURE:
Antitumoral medicinal composition obtained by dissolving the crystallized boric acid in 800 ml of sodium chloride solution 8,5-9°/00, whereby 2 ml of 4-amino-benzoyl-diethylamino-ethanol chlorhydrate, solution 8% and 10 ml ascorbic acid, solution 10% are added; then distilled water is added up to 1000 ml; the resulting solution is heated at 100°C, for 20 to 60 minutes, sterilized and filtered; the final pH is 5 to 6. The weight ratio between 4-amino-benzoyldiethylamino-ethanol-chlorhydrate, boric acid and ascorbic acid is: 1 :
(0,62-1,9) : 6,25. 1 to 5 ml product shall be administered daily, for 20 days, by intravenous route, drop by drop, at intervals of 5 to 6 seconds between the drops; the cycle of 20 administrations shall be repeated 3 to 5 times at intervals of 5 to 10 days.
Antitumoral medicinal composition obtained by dissolving the crystallized boric acid in 800 ml of sodium chloride solution 8,5-9°/00, whereby 2 ml of 4-amino-benzoyl-diethylamino-ethanol chlorhydrate, solution 8% and 10 ml ascorbic acid, solution 10% are added; then distilled water is added up to 1000 ml; the resulting solution is heated at 100°C, for 20 to 60 minutes, sterilized and filtered; the final pH is 5 to 6. The weight ratio between 4-amino-benzoyldiethylamino-ethanol-chlorhydrate, boric acid and ascorbic acid is: 1 :
(0,62-1,9) : 6,25. 1 to 5 ml product shall be administered daily, for 20 days, by intravenous route, drop by drop, at intervals of 5 to 6 seconds between the drops; the cycle of 20 administrations shall be repeated 3 to 5 times at intervals of 5 to 10 days.
Description
2~3~i5 The present invention refers to an antitumoral pharmaceutical composition, to its process of preparation, as well as to the prophylaxis and treatment method oE the tumors.
Various chemical substances and compositions used in the treatment oE tumors are known. Out of them, an important place is taken by cytostatics, cytolytics, immunotherapeutic and immunosuppressive substances. Besides, radiotherapeutic and surgical methods can be used in the treatment of tumors.
The cytostatics and cytolytics do not hinder the evolution of the disease. The former have an effect in some cases, in that they stop the development of the tumors, whereas the latter also partially destroy the neoplastic cells, this destruction taking place in the middle of the tumors in this kind of treatment.
Although with certain results in some cases, Rontgen-therapy and cobaltotherapy, besides the local action over the tumors, given the effect of irradiations, unfavourably influence the physiological condition of the whoLe body.
It is also known that surgical interventions remove tumors by excision, however metastases are likely to occur in most of the cases.
It is also a fact that 4-amino-benzoyldiethylamino-ethanol chlorhydrate (procaine) is used in local anesthesias.
Its use in geriatry has also been known for some time, due to its capacity to bind free radicals in older tissues.
Known is also the capacity of the borine to accumulate in tumors, and, as a recent application of this property, the radiotherapeutic treatment method of cancer is known, by irradiation of the tumor with a neutron beam, after a previous borine administration.
S
Already in the fourties of this century, one used to anesthesic purposes the borine products with aminated bases, known under the general denomination of boramines.
It is known that Vitamin C appears in a low concen~ra- .
tion in the blood of the patients with neoplasies, and that the synthesis of collagen, includlng the capacity of the body to form barriers against tumor expansion, is carried on with a high consumption of Vitamin C.
The pharmaceutical composition a~cordlng to the inven tion consists of a syner~istic composition of boric acid, 4-amino-benzoyldie-thylamino-ethanol chlorhydrate (procaine) and Vitamin C in an isotonic solution of sodium chloride, the proportions of the active ingredlents being established so as to rearch a final pH of 5-6 of the resulting solution.
The association of the 3 active ingredients in the injectable solution with final pH of 5-6 is so chosen as to allow, by a special administration, the following specific effects of the produc-t:
- achievement of an optimal concentration of borate ion, in order to react at the level of the cell receivers so as to enable the incorporation of the borate ions within the struc-ture of aminoacids in malign tumors and acting on a competitive basis with the phosphate ion;
- easy binding of 4-amino-benzoyldiethylamino-ethanol chlorhydrate (substance which is completely dissociated in -the product of the invention) to the free radicals existing in the cancer tumors, the radicals having a higher concentration in the malign tumors than the free radicals of the healthy tissues, this tumor derives from;
- achievement of a certain pH to facilitate the simultaneous action of the borate ion and of the ~-amino~benzoyl-2~5 diethylamino-ethanol chlorhydrate (procaine?, by associa-tion of the ascorbic acid, which, together with the boric acid o:E the product, makes up a buEfer mixture that is effective in mainta.ining the pH within the values 5-6;
- administration of the product of this invention in a special way,i.e. daily, i.e.administration drop by drop, for 20 days running in increasing doses from 1-5 ml, allows an optimal absorption at tumoral level of the active ingredients, which simultaneously makes it possible for the cell receivers to regenerate.
The process according to the invention provides for khe solubilisation of 0,10 - 0,30 g boric acid crystallized in 800 ml solution 8,5 - 9 per thousand chloride, after which 2 mi, 8 per cent solution 4-amino-benzoyldiethylamino-ethanol chlorhydrate (procaine) and 10 ml, 10 per cent solution Vitamin C are added.
~eat resulting solution at 100C, for 20 - 60 minutes, then filter, pour into ampoules an~d sterilize according to known methods which means filtering through a multipore filter 0.45 ~m pouring into ampoules and sterilizing by maintaining the ampoules in an autoclave for 20 minutes, at a temperature of 120C.
The treatment method of neoplasm, using the product according to the invention, consists of the i.v. administration of the product daily, for 20 days running, in increasing doses from 1 - S ml, drop by drop, at intervals of 5 ~ 6 seconds between the drops, whereby the cycle of 20 administrations shall be repeated 3 ~ 5 times, at intervals varying between 5-10 days, depending on the symptomatic range displayed by the patient.
See below two far from limitating examples as to how the invention is done.
2~3~5 ~XAMPLE l Distil non-chlorinated and non-fluorinated water.
Prepare with thus distilled water a solution of 8,5 - 9 per thousand sodium chloride. Dissolve into 800 ml of this solution 0,10 g crystallized boric acid of pharmaceutical quality, then add 2 ml,8~ solution of 4-amino-benzoyldiethylamino-ethanol chlorhydrate (procaine) and lO ml~lO per cent Vitamin C solution.
Bring to l,000 ml with distilled water, thus obtaining a solution with p~ between 5 - 6.
Heat the solution for 20 minutes at a temperature of 100C.
Filter the hot solution, pour it into ampoules and sterilize it.
Distil non-chlorinated and non-fluorina-ted water.
Out of the thus distilled water, prepare a solution of 8,5 - 9 per thousand chemically pure sodium chloride. In 800 ml of the solution of sodium chloride obtained in this way, dissolve 0,3 g crystallized boric acid of pharmaceutical quality, then add 2 ml 8 per cent solution of 4-amino-benzoyldiethylamino-ethanol chlorhydrate (procaine) and lO ml lO~ solution of Vitamin C. ~he resulting solution has a pH of 5 - 6 and is brought to l,000 ml with distilled water. Keep the solution at 100C for 60 minutes.
Filter the hot solution, pour it into ampoules and sterilize it.
The treatment method, using the product according to the invention, provides its intravenous administration under the following conditions:
Inject daily, over a 20-day-period, with a syringe ha~ing an 18-20 needly increasing amounts of 1-5 ml selution, drop by drop, at intervals of 5-6 seconds between the drops.
-- 4 ~
.~, ~
The cyc~e of 20 administrations shall be repeated 3 -5 times, at intervals of 5 - 10 days, depending on the symptoma-tic range displayed by the patient.
It is advisable to check the proteinurie during the treatment.
As at the beginning of the treatment with the product according to the invention one may feel certain itchings, pricklings, prurite or smarting pains, the treatment method may also be used as a method of informative dlagnosis.
The advantages of the product according to the invention are as follows: ~
- leads to the regressions of neoplastic tumors;
- does not alter the blood formula;
- restores and preserves the acid-base balance at humoral level;
- improves the patient's general condition; the pains disappear as soon as the first injections are administered;
- it has no contraindications and may be associated with treatments for ~other diseases.
Various chemical substances and compositions used in the treatment oE tumors are known. Out of them, an important place is taken by cytostatics, cytolytics, immunotherapeutic and immunosuppressive substances. Besides, radiotherapeutic and surgical methods can be used in the treatment of tumors.
The cytostatics and cytolytics do not hinder the evolution of the disease. The former have an effect in some cases, in that they stop the development of the tumors, whereas the latter also partially destroy the neoplastic cells, this destruction taking place in the middle of the tumors in this kind of treatment.
Although with certain results in some cases, Rontgen-therapy and cobaltotherapy, besides the local action over the tumors, given the effect of irradiations, unfavourably influence the physiological condition of the whoLe body.
It is also known that surgical interventions remove tumors by excision, however metastases are likely to occur in most of the cases.
It is also a fact that 4-amino-benzoyldiethylamino-ethanol chlorhydrate (procaine) is used in local anesthesias.
Its use in geriatry has also been known for some time, due to its capacity to bind free radicals in older tissues.
Known is also the capacity of the borine to accumulate in tumors, and, as a recent application of this property, the radiotherapeutic treatment method of cancer is known, by irradiation of the tumor with a neutron beam, after a previous borine administration.
S
Already in the fourties of this century, one used to anesthesic purposes the borine products with aminated bases, known under the general denomination of boramines.
It is known that Vitamin C appears in a low concen~ra- .
tion in the blood of the patients with neoplasies, and that the synthesis of collagen, includlng the capacity of the body to form barriers against tumor expansion, is carried on with a high consumption of Vitamin C.
The pharmaceutical composition a~cordlng to the inven tion consists of a syner~istic composition of boric acid, 4-amino-benzoyldie-thylamino-ethanol chlorhydrate (procaine) and Vitamin C in an isotonic solution of sodium chloride, the proportions of the active ingredlents being established so as to rearch a final pH of 5-6 of the resulting solution.
The association of the 3 active ingredients in the injectable solution with final pH of 5-6 is so chosen as to allow, by a special administration, the following specific effects of the produc-t:
- achievement of an optimal concentration of borate ion, in order to react at the level of the cell receivers so as to enable the incorporation of the borate ions within the struc-ture of aminoacids in malign tumors and acting on a competitive basis with the phosphate ion;
- easy binding of 4-amino-benzoyldiethylamino-ethanol chlorhydrate (substance which is completely dissociated in -the product of the invention) to the free radicals existing in the cancer tumors, the radicals having a higher concentration in the malign tumors than the free radicals of the healthy tissues, this tumor derives from;
- achievement of a certain pH to facilitate the simultaneous action of the borate ion and of the ~-amino~benzoyl-2~5 diethylamino-ethanol chlorhydrate (procaine?, by associa-tion of the ascorbic acid, which, together with the boric acid o:E the product, makes up a buEfer mixture that is effective in mainta.ining the pH within the values 5-6;
- administration of the product of this invention in a special way,i.e. daily, i.e.administration drop by drop, for 20 days running in increasing doses from 1-5 ml, allows an optimal absorption at tumoral level of the active ingredients, which simultaneously makes it possible for the cell receivers to regenerate.
The process according to the invention provides for khe solubilisation of 0,10 - 0,30 g boric acid crystallized in 800 ml solution 8,5 - 9 per thousand chloride, after which 2 mi, 8 per cent solution 4-amino-benzoyldiethylamino-ethanol chlorhydrate (procaine) and 10 ml, 10 per cent solution Vitamin C are added.
~eat resulting solution at 100C, for 20 - 60 minutes, then filter, pour into ampoules an~d sterilize according to known methods which means filtering through a multipore filter 0.45 ~m pouring into ampoules and sterilizing by maintaining the ampoules in an autoclave for 20 minutes, at a temperature of 120C.
The treatment method of neoplasm, using the product according to the invention, consists of the i.v. administration of the product daily, for 20 days running, in increasing doses from 1 - S ml, drop by drop, at intervals of 5 ~ 6 seconds between the drops, whereby the cycle of 20 administrations shall be repeated 3 ~ 5 times, at intervals varying between 5-10 days, depending on the symptomatic range displayed by the patient.
See below two far from limitating examples as to how the invention is done.
2~3~5 ~XAMPLE l Distil non-chlorinated and non-fluorinated water.
Prepare with thus distilled water a solution of 8,5 - 9 per thousand sodium chloride. Dissolve into 800 ml of this solution 0,10 g crystallized boric acid of pharmaceutical quality, then add 2 ml,8~ solution of 4-amino-benzoyldiethylamino-ethanol chlorhydrate (procaine) and lO ml~lO per cent Vitamin C solution.
Bring to l,000 ml with distilled water, thus obtaining a solution with p~ between 5 - 6.
Heat the solution for 20 minutes at a temperature of 100C.
Filter the hot solution, pour it into ampoules and sterilize it.
Distil non-chlorinated and non-fluorina-ted water.
Out of the thus distilled water, prepare a solution of 8,5 - 9 per thousand chemically pure sodium chloride. In 800 ml of the solution of sodium chloride obtained in this way, dissolve 0,3 g crystallized boric acid of pharmaceutical quality, then add 2 ml 8 per cent solution of 4-amino-benzoyldiethylamino-ethanol chlorhydrate (procaine) and lO ml lO~ solution of Vitamin C. ~he resulting solution has a pH of 5 - 6 and is brought to l,000 ml with distilled water. Keep the solution at 100C for 60 minutes.
Filter the hot solution, pour it into ampoules and sterilize it.
The treatment method, using the product according to the invention, provides its intravenous administration under the following conditions:
Inject daily, over a 20-day-period, with a syringe ha~ing an 18-20 needly increasing amounts of 1-5 ml selution, drop by drop, at intervals of 5-6 seconds between the drops.
-- 4 ~
.~, ~
The cyc~e of 20 administrations shall be repeated 3 -5 times, at intervals of 5 - 10 days, depending on the symptoma-tic range displayed by the patient.
It is advisable to check the proteinurie during the treatment.
As at the beginning of the treatment with the product according to the invention one may feel certain itchings, pricklings, prurite or smarting pains, the treatment method may also be used as a method of informative dlagnosis.
The advantages of the product according to the invention are as follows: ~
- leads to the regressions of neoplastic tumors;
- does not alter the blood formula;
- restores and preserves the acid-base balance at humoral level;
- improves the patient's general condition; the pains disappear as soon as the first injections are administered;
- it has no contraindications and may be associated with treatments for ~other diseases.
Claims (2)
1. A synergistic antitumoral pharmaceutical composi-tion consisting essentially of a synergistic association of 4-amino-benzoyldiethylamino-ethanol chlorhydrate with boric acid and ascorbic acid in a 3.5 to 9 per thousand aqueous injectable solution of sodium chloride, with a pH between 5-6, wherein the weight ratio of the 4-amino-benzoyldiethylamino-ethanol chlorhydrate, boric acid and ascorbic acid is respectively 1 :
(0.62-1.9) : 6.25 and wherein the amount of 4-amino-benzoyl-diethylamino-ethanol chlorhydrate in the injectable solution is 0.16 g%, the amount of boric acid in the injectable solution is between 0.1 - 0.3 g%, and the amount of ascorbic acid in the injectable solution is 1 g%.
(0.62-1.9) : 6.25 and wherein the amount of 4-amino-benzoyl-diethylamino-ethanol chlorhydrate in the injectable solution is 0.16 g%, the amount of boric acid in the injectable solution is between 0.1 - 0.3 g%, and the amount of ascorbic acid in the injectable solution is 1 g%.
2. Process for the preparation of a composition as defined in claim 1, which comprises dissolving the crystallized boric acid in the solution of sodium chloride 8,5 - 9 %, then adding to the thus obtained solution 2 ml 8% solution of 4-amino-benzoyldiethylamino-ethanol chlorhydrate and 10 ml 10%
solution of ascorbic acid, bringing it then to 1000 ml with distilled water; heating the resulting solution at 100°C for 20-60 minutes, then filtering it through a multipore filter 0.45 µm; pouring it into ampoules and sterilizing it by main-taining the ampoules in an autoclave for 20 minutes, at a temperature of 120°C.
solution of ascorbic acid, bringing it then to 1000 ml with distilled water; heating the resulting solution at 100°C for 20-60 minutes, then filtering it through a multipore filter 0.45 µm; pouring it into ampoules and sterilizing it by main-taining the ampoules in an autoclave for 20 minutes, at a temperature of 120°C.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| RO97934 | 1979-06-23 | ||
| RO7997934A RO72294A2 (en) | 1979-06-23 | 1979-06-23 | ANTICANCER DRUG PRODUCT AND PREPARATION METHOD |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1142855A true CA1142855A (en) | 1983-03-15 |
Family
ID=20106169
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000354516A Expired CA1142855A (en) | 1979-06-23 | 1980-06-20 | Antitumoral composition and its process of preparation |
Country Status (5)
| Country | Link |
|---|---|
| CA (1) | CA1142855A (en) |
| DE (1) | DE3023396C2 (en) |
| ES (1) | ES8104912A1 (en) |
| FR (1) | FR2459659A1 (en) |
| RO (1) | RO72294A2 (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0875246A1 (en) * | 1997-04-04 | 1998-11-04 | Showa Denko Kabushiki Kaisha | Pharmaceutical preparation of ascorbic acid derivatives for medical treatment of cancer |
| RO116524B1 (en) * | 1999-05-26 | 2001-03-30 | M. Corneliu Niculescu | Antineoplastic pharmaceutical product for human and veterinary use, preparation process thereof and method of antineoplastic treatment |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2684323A (en) * | 1950-10-21 | 1954-07-20 | Physiological Chemicals Compan | Procaine ascorbate preparation |
| FR3385M (en) * | 1963-12-02 | 1965-06-21 | Sobio Lab | Therapeutic compositions based on procaine ascorbate. |
-
1979
- 1979-06-23 RO RO7997934A patent/RO72294A2/en unknown
-
1980
- 1980-06-16 ES ES492468A patent/ES8104912A1/en not_active Expired
- 1980-06-20 CA CA000354516A patent/CA1142855A/en not_active Expired
- 1980-06-20 FR FR8013763A patent/FR2459659A1/en active Granted
- 1980-06-23 DE DE19803023396 patent/DE3023396C2/en not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| DE3023396C2 (en) | 1983-02-17 |
| FR2459659A1 (en) | 1981-01-16 |
| FR2459659B1 (en) | 1983-05-27 |
| RO72294A2 (en) | 1982-12-06 |
| ES492468A0 (en) | 1981-05-16 |
| ES8104912A1 (en) | 1981-05-16 |
| DE3023396A1 (en) | 1981-01-22 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MKEX | Expiry |