US3265574A - Method of enhancing the effect of X-ray and radium treatment - Google Patents
Method of enhancing the effect of X-ray and radium treatment Download PDFInfo
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- US3265574A US3265574A US270189A US27018963A US3265574A US 3265574 A US3265574 A US 3265574A US 270189 A US270189 A US 270189A US 27018963 A US27018963 A US 27018963A US 3265574 A US3265574 A US 3265574A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
- A61K51/12—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by a special physical form, e.g. emulsion, microcapsules, liposomes, characterized by a special physical form, e.g. emulsions, dispersions, microcapsules
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
- A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
- A61K51/12—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by a special physical form, e.g. emulsion, microcapsules, liposomes, characterized by a special physical form, e.g. emulsions, dispersions, microcapsules
- A61K51/1258—Pills, tablets, lozenges
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/37—Esters of carboxylic acids
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
- A61Q17/04—Topical preparations for affording protection against sunlight or other radiation; Topical sun tanning preparations
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2121/00—Preparations for use in therapy
Definitions
- the compounds to be used to attain the above described new and unexpected result are represented by three derivatives of cyclohexanol, namely by the sodium salt of cyclohexanol succinate, by cyclohexanol palmitate, and cyclohexanol stearate.
- the rats were submitted to a total radiation of 600 R. administered in one treatment only, and with the following values: 200 kv., l8 ma., filter 0.5 cu., dpf 50 cm., r./m. 57.5.
- the tests were carried out on three rat groups, each formed by ten. rats, having an average Weight of 200 gr. per rat.
- the first of said groups was treated with peritoneally administered doses of sodium cyclohexanol succinate amounting to 300 mg. per kg.; the second group was treated, over a five consecutive day period, with a dose of 300 mg./kg., while the third group was treated with physiological solution (control group).
- the mode of administering the products to patients was as follows:
- Tablets.-Two tablets of active product 250 mg. each) at intervals of 6 hours, (total dose per day: 2 g.). The administration was always effected in the course of 24 hrs. preceding radiation treatment.
- This daily dose was maintained during the whole course of radium-therapy and sometimes even for longer periods to act also on the restoration phaenomena of the tumor cells.
- Phials.l g. of active product was intramuscularly administered on the day preceding the radiation treatment, and one phial (l g.) directly before said treatment or, in the case of radium therapy, a phail daily during the whole treatment. Phails were used also for intraand peritumoral infiltrations, directly before radium therapy, or for cases which required a quicker and more intense action.
- the products with which the invention is concerned may be considered valuable therapeutic aids since for a given therapeutic effect they allow the use of lesser amounts of radiating energy, with consequent lesser damage to the connective tissues of the tumor bed and furthermore they render radiation-resistant forms of cancer capable of being treated and improved by usual radiation treatments.
- cyclohexanol derivatives with which the invention is concerned appear suitable as potentiating agents in the radiotherapy of epitheliomas as well as for decreasing or minimizing radioresistance which arises in cases of recurrence after a first actinic treatment.
- the method by which the sodium cyclohexanol succinate (this being the preferred product) can be obtained consists of having succinic anhydride reacted with cyclohexanol alcohol, thereby obtaining the cyclohexanolsuccinic acid which is then reacted with sodium hydroxide.
- the cyclohexilic acid is to be gradually added in stoichiometric amounts to the succinic anhydride under rather mild temperature conditions (i.e. about 110 C.), whereafter the reaction product is extracted with water and benzene, avoiding any treatment with acids or bases which, owing to the extreme facility with which the cyclohexanol succinic acid is saponified, would unavoidably result in the formation of undesirable products.
- the final crystallization is preferably carried out from ligroin.
- the above method allows to obtain a product (melting point 50-51 C.) which shows a practically theoretical centesimal content of carbon-hydrogen and which can be converted into a salt with an accurate equivalent amount of sodium hydroxide, using phenolphthalein as indicator.
- the corresponding sodium salt was obtained by adding at room temperature an accurate equivalent of sodium hydroxide to an alcoholic solution of the acid, whereupon the resulting solution was concentrated to dryness under vacuum. Since, as already stated, the thus-obtained substance is rather sensitive with respect to acids and alkaline agents the solution is preferably adjusted to a pH value lower than 8 prior to being concentrated.
- the pulverized sodium salt is repeatedly washed with acetone.
- the final product is obtained in the form of a white powder, ve-ry soluble in water, soluble in alcohol at 90 C., and insoluble in the usual organic solvents.
- the product can be further purified by dissolving it in alcohol at 90 0., followed by precipitation with ether. Melting point: 178-l80 C.
- the aqueous solutions of said product after an adjustment of pHvalue to 7.2 by means of citric acid or phosphoric acid, do not undergo any changes as consequence of heating at 110 C. for a period of one hour.
- the methods for preparing the cyclohexanol derivatives will be disclosed in more detail in the following examples, of which the first one relates to the preparation of a high purity cyclohexanol succinic acid, the second relates to the conversion thereof into a sodium salt, the third to the preparation of cyclohexanol palmitate, and the fourth to the preparation of cyclohexanol stearate.
- Example I g. of succinic anhydride were put into a three-necked, round bottomed fiask, equipped with a cooler, a stirrer and a separating funnel, and heated up to melting temperature (120 C.). Then 50 g. of cyclohexanolic acid were gradually added, while stirring and keeping the inside temperature of the flask at 100-110 C. After the end of such addition, the reaction mass was kept for about half an hour at 100 C., and then cooled. Subseqeuntly the mass was alternately taken up with equal volumes of water and benzene, until the entire substance was dissolved. The benzene layer, dehydrated with sodium sulphate, was evaporated to dryness, and the residue was taken up in boiling ligroin.
- the ligroin solution was filtered, and after cooling, the separated crystals were collected on a filter, under vacuum.
- Example 2 50 g. of cyclohexanolsuccinic acid, obtained according to Example 1, were dissolved in 200 cc. of abs. ethyl alcohol, and then added to an equivalent amount (10 g.) of sodium hydroxide in the form of a concentrated aqueous solution. The resulting solution was evaporated under vacuum to dryness, and the residue, consistingof a white mass, was pulverized and repeatedly washed with acetone.
- Example 3 200 cc. anhydride pyridine and 20 g. cyclohexanol (2 moles) were poured in a 500 cc. flask equipped with a stirrer. To the thus obtained solution were added under stirring g. (0.2 mole) of palmitoil chloride. The addition has to be effected slowly since the reaction is of strongly exothermic nature. Thereafter the reactive mixture was kept at room temperature for 36 hours. -On completion of the reaction the reaction mixture was introduced drop by drop through a separating funnel into 700 cc. of strongly agitated cold water.
- the precipitate was filtered under vacuum, washed with a great amount of Water and then dried under vacuum.
- the product obtained melts at 30.5-320 C. and can contain up to 9% of palmitic acid. It crystallizes from alcohol (7 volumes) with a -82% yield. Melting point 33.5-34.5 C. Free palmitic acid being absent.
- Example 4 To 300 cc. of anhydrous pyridine containing 40 g. (0.4 mole) cyclohexanol were added through a separating funnel under stirring 121 g. (0.4 mole) stearoyl chloride strong heating occurs and the mixture becomes yellow. After this addition, the reaction vessel was closed and kept at room temperature for 36 hours. Then the reaction mixture was poured under strong agitation into 1500 cc. of very cold water. The precipitate was filtred under vacuum and repeatedly washed with a cold 4% solution of bicarbonate, then with a great amount of cold water until the alkalinity disappeared. Then it was dried under vacuum. The dried product (-140 g.) was free from free stc-aric acid. Melting point: 37-38 C.
- a method of enhancing the effect of X-ray and radium treatment of a patient which comprises first administering to said patient an effective amount of sodium cyclohexanol succinate, and thereafter subjecting said patient to X-ray or radium treatment, whereby the eifect of the X-ray or radium treatment is enhanced by the preceding administration of said sodium cyclohexanol succinate.
Description
'tumor-ous tissues.
United States Patent 3,265,574 METHOD OF ENHANQING THE EFFECT OF X-RAY AND RADIUM TREATMENT Giuseppe Enea Scolari, Via Degli Alfani 37, Florence, Italy No Drawing. Filed Apr. 3, 1963, Ser. No. 270,189 Claims priority, application Italy, Apr. 7, 1962, 6,986/ 62 4 Claims. (Cl. 167-65) The present invention relates to X-rays potentiating compounds and more particularly to compounds capable to suppress the inherent or acquired radiation resistance of given tissues of the human body.
One of the most widely applied curvative methods for tumors, is based on the action of ionizing radiation on It is known that no efficient intervention is possible against X-ray resistance or recurring tumorous formations, which consequently require, for their treatment, other more intricate and complex therapeutical procedures. As a rule, a tumor not healed by a first radiation treatment, is not likely to yield to a second one, and will nearly never recede upon a third irradiation. Furthermore, if subsequent X-ray treatments are similar to their first one, with respect to equipment, technique and dosage used, then the chances of a successful outcome are as good as negligible.
Surprisingly, it has been discovered that a series of chemical compounds, While being without any medicamental activity per se, are capable of sensitizing tumorous tissues to X-ray radiations which tumorous tissues would be unattackable, or at least not successfully treatable, by ionizing radiations.
Experiments conducted on animals and on human beings have shown that by administering the compounds according to the invention, the arising of X-ray resistant phenomena can be reduced and the patient submitted to many, subsequent X-rray treatments, thus avoiding the necessity to resort to more complicated techniques for eliminating cancer.
- The compounds to be used to attain the above described new and unexpected result are represented by three derivatives of cyclohexanol, namely by the sodium salt of cyclohexanol succinate, by cyclohexanol palmitate, and cyclohexanol stearate.
Experimental results have confirmed the potentiating properties of these compounds on the biological action of radiation, since an ineffective or palliative radiologic treatment has become effective and radical in a very high percentage of cases treated with these compounds.
To demonstrate the X-ray sensitizing properties possessed by these compounds, the following tests were conducted on rats. The rats were submitted to a total radiation of 600 R. administered in one treatment only, and with the following values: 200 kv., l8 ma., filter 0.5 cu., dpf 50 cm., r./m. 57.5. The tests were carried out on three rat groups, each formed by ten. rats, having an average Weight of 200 gr. per rat. The first of said groups was treated with peritoneally administered doses of sodium cyclohexanol succinate amounting to 300 mg. per kg.; the second group was treated, over a five consecutive day period, with a dose of 300 mg./kg., while the third group was treated with physiological solution (control group).
All tests proved that the compound in question is able to exert a marked radiosensitizing action, which manifests itself both in a higher mortality ratio after the end of tests and in a quicker reaching of the effects in the radiated animals.
In fact, a destructive effect of radiations was ascertained already during the second day of treatment and after 30 days the mortality percentage was decidedly higher than that of the control group.
Clinical tests on patients affected by tumors by treatment with average daily doses amounting to 2 g. of the products indicated above (that may be administered in the form of tablets or if soluble, of phials) have also provedthe radiation sensitizing effect of the products.
A very low toxicity and a wide margin of tolerance have also been shown by the products.
The mode of administering the products to patients was as follows:
Tablets.-Two tablets of active product (250 mg. each) at intervals of 6 hours, (total dose per day: 2 g.). The administration was always effected in the course of 24 hrs. preceding radiation treatment.
This daily dose was maintained during the whole course of radium-therapy and sometimes even for longer periods to act also on the restoration phaenomena of the tumor cells.
Phials.l g. of active product was intramuscularly administered on the day preceding the radiation treatment, and one phial (l g.) directly before said treatment or, in the case of radium therapy, a phail daily during the whole treatment. Phails were used also for intraand peritumoral infiltrations, directly before radium therapy, or for cases which required a quicker and more intense action.
The following results were obtained by administering the above indicated doses:
(A) After the first treatment, in which half of the standard radiation dose was administered, recovery was ascertained in of epithelomas cases treated; in the remaining 25% cases, the treatment was completed by diatheromocoagulation ordue to nature of the cutaneous neoplasm treated-it was deemed proper to at-minister the whole radiation dose.
(B) After treatment with the whole radiation dose 78.5% of recovery was ascertained in cases of epithelial and mucous tumors recurring or resisting to a first radiological treatment.
The products with which the invention is concerned may be considered valuable therapeutic aids since for a given therapeutic effect they allow the use of lesser amounts of radiating energy, with consequent lesser damage to the connective tissues of the tumor bed and furthermore they render radiation-resistant forms of cancer capable of being treated and improved by usual radiation treatments.
Clinical tests have been performed in order to evidence the possibility of increasing the interval between tumoricide ionizing radiations and the doses which are harmful to normal tissues and to determine the modes of administration.
These tests have been conducted on 40 patients affected by cutaneous and mucous neoplasms recurring or resistant to radium therapy.
From the examination of the results, it may be concluded that:
(1) In 75 of the treated cases complete involution of the tumoral process was obtained after the first treatment, although radiation was carried out with half of the standard radiation doses. The increase in the biological radiation eifect attained by administration of 2 g. per day of the cyclohexanol derivatives per os or parenterally can be evaluated about 50%.
(2) Local recurrences of already radiated epitheliomas, which generally show a radio-resistant behaviour, will again attain a sensitivity allowing the same to be again treated by a simple radiologic technique and with very good results (75% of recovery).
(3) The cyclohexanol derivatives with which the invention is concerned appear suitable as potentiating agents in the radiotherapy of epitheliomas as well as for decreasing or minimizing radioresistance which arises in cases of recurrence after a first actinic treatment.
(4) The lesser amount of radiating energy used, which however allows obtention of the required therapeutic effect due to administration of the cyclohexanol derivatives, represents an advantage in that lesser damages are suffered by the healthy peritumoral tissues, which therefore maintain a higher reactive and recovery power with respect to the irradiated morbid focus.
The method by which the sodium cyclohexanol succinate (this being the preferred product) can be obtained consists of having succinic anhydride reacted with cyclohexanol alcohol, thereby obtaining the cyclohexanolsuccinic acid which is then reacted with sodium hydroxide.
A material importance is to be attached to the method used by the inventors, for the preparation of a high purity cyclohexanol-succinic acid. For this purpose, the cyclohexilic acid is to be gradually added in stoichiometric amounts to the succinic anhydride under rather mild temperature conditions (i.e. about 110 C.), whereafter the reaction product is extracted with water and benzene, avoiding any treatment with acids or bases which, owing to the extreme facility with which the cyclohexanol succinic acid is saponified, would unavoidably result in the formation of undesirable products. Moreover, due to the high degree of solubility of the cyclohexanol succinic acid in ethyl alcohol, the final crystallization is preferably carried out from ligroin.
The above method allows to obtain a product (melting point 50-51 C.) which shows a practically theoretical centesimal content of carbon-hydrogen and which can be converted into a salt with an accurate equivalent amount of sodium hydroxide, using phenolphthalein as indicator.
The corresponding sodium salt was obtained by adding at room temperature an accurate equivalent of sodium hydroxide to an alcoholic solution of the acid, whereupon the resulting solution was concentrated to dryness under vacuum. Since, as already stated, the thus-obtained substance is rather sensitive with respect to acids and alkaline agents the solution is preferably adjusted to a pH value lower than 8 prior to being concentrated.
To positively prevent the always possible formation of small amounts of impurities, which can be identified by the opalescence of aqueous solutions, the pulverized sodium salt is repeatedly washed with acetone.
The final product is obtained in the form of a white powder, ve-ry soluble in water, soluble in alcohol at 90 C., and insoluble in the usual organic solvents.
The product can be further purified by dissolving it in alcohol at 90 0., followed by precipitation with ether. Melting point: 178-l80 C. The aqueous solutions of said product, after an adjustment of pHvalue to 7.2 by means of citric acid or phosphoric acid, do not undergo any changes as consequence of heating at 110 C. for a period of one hour.
The methods for preparing the cyclohexanol derivatives will be disclosed in more detail in the following examples, of which the first one relates to the preparation of a high purity cyclohexanol succinic acid, the second relates to the conversion thereof into a sodium salt, the third to the preparation of cyclohexanol palmitate, and the fourth to the preparation of cyclohexanol stearate.
Example I g. of succinic anhydride were put into a three-necked, round bottomed fiask, equipped with a cooler, a stirrer and a separating funnel, and heated up to melting temperature (120 C.). Then 50 g. of cyclohexanolic acid were gradually added, while stirring and keeping the inside temperature of the flask at 100-110 C. After the end of such addition, the reaction mass was kept for about half an hour at 100 C., and then cooled. Subseqeuntly the mass was alternately taken up with equal volumes of water and benzene, until the entire substance was dissolved. The benzene layer, dehydrated with sodium sulphate, was evaporated to dryness, and the residue was taken up in boiling ligroin.
The ligroin solution was filtered, and after cooling, the separated crystals were collected on a filter, under vacuum.
Yield: 78 g. Melting point 505l C.
Example 2 50 g. of cyclohexanolsuccinic acid, obtained according to Example 1, were dissolved in 200 cc. of abs. ethyl alcohol, and then added to an equivalent amount (10 g.) of sodium hydroxide in the form of a concentrated aqueous solution. The resulting solution was evaporated under vacuum to dryness, and the residue, consistingof a white mass, was pulverized and repeatedly washed with acetone.
Thereafter, the powder was taken up with the smallest possible volume of alcohol at 90 C., and allowed to crystallize in a very cool room.
Example 3 200 cc. anhydride pyridine and 20 g. cyclohexanol (2 moles) were poured in a 500 cc. flask equipped with a stirrer. To the thus obtained solution were added under stirring g. (0.2 mole) of palmitoil chloride. The addition has to be effected slowly since the reaction is of strongly exothermic nature. Thereafter the reactive mixture was kept at room temperature for 36 hours. -On completion of the reaction the reaction mixture was introduced drop by drop through a separating funnel into 700 cc. of strongly agitated cold water.
The precipitate was filtered under vacuum, washed with a great amount of Water and then dried under vacuum.
The product obtained melts at 30.5-320 C. and can contain up to 9% of palmitic acid. It crystallizes from alcohol (7 volumes) with a -82% yield. Melting point 33.5-34.5 C. Free palmitic acid being absent.
Example 4 To 300 cc. of anhydrous pyridine containing 40 g. (0.4 mole) cyclohexanol were added through a separating funnel under stirring 121 g. (0.4 mole) stearoyl chloride strong heating occurs and the mixture becomes yellow. After this addition, the reaction vessel was closed and kept at room temperature for 36 hours. Then the reaction mixture was poured under strong agitation into 1500 cc. of very cold water. The precipitate was filtred under vacuum and repeatedly washed with a cold 4% solution of bicarbonate, then with a great amount of cold water until the alkalinity disappeared. Then it was dried under vacuum. The dried product (-140 g.) was free from free stc-aric acid. Melting point: 37-38 C.
I claim:
1. A method of enhancing the effect of X-ray and radium treatment of a patient which comprises first administering to said patient an effective amount of sodium cyclohexanol succinate, and thereafter subjecting said patient to X-ray or radium treatment, whereby the eifect of the X-ray or radium treatment is enhanced by the preceding administration of said sodium cyclohexanol succinate.
5 2. A method of enhancing the elfect of X-ray and radium treatment-of a patient as defined in claim 1, wherein said sodium cyclohexanol succinate is administered in a daily dosage of between 1 and 2 grams.
3. A method of enhancing the effect of X-ray and radium treatment of a patient as defined in claim 1, wherin said sodium cyclohexanol succinate is administered perorally.
4. A method of enhancing the effect of X-ray and radium treatment of a patient as defined in claim 1, wherein said sodium cyclohexanol succinate is administered instramuscularly.
No references cited. 7
J-ULIAN S. LEVITT, Primary Examiner.
FRANK S. CACCIAIPAGLIA, JR., Examiner.
P. L. SABAT-IN-E, Assistant Examiner.
Claims (1)
1. A METHOD OF ENHANCING THE EFFECT OF X-RAY AND RADIUM TREATMENT OF A PATIENT WHICH COMPRISES FIRST ADMINISTERING TO SAID PATIENT AN EFFECTIVE AMOUNT OF SODIUM CYCLOHEXANOL SUCCINATE, AND THEREAFTER SUBJECTING SAID PATIENT TO X-RAY OR RADIUM TREATMENT, WHEREBY THE EFFECT OF THE X-RAY OR RADIUM TREATMENT IS ENHANCED BY THE PRECEDING ADMINISTRATION OF SAID SODIUM CYCLOHEXANOL SUCCINATE.
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
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IT698662 | 1962-04-07 |
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US3265574A true US3265574A (en) | 1966-08-09 |
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US270189A Expired - Lifetime US3265574A (en) | 1962-04-07 | 1963-04-03 | Method of enhancing the effect of X-ray and radium treatment |
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FR (1) | FR2625M (en) |
Cited By (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6634413B2 (en) | 2001-06-11 | 2003-10-21 | Santoku America, Inc. | Centrifugal casting of nickel base superalloys in isotropic graphite molds under vacuum |
US6705385B2 (en) | 2001-05-23 | 2004-03-16 | Santoku America, Inc. | Castings of metallic alloys with improved surface quality, structural integrity and mechanical properties fabricated in anisotropic pyrolytic graphite molds under vacuum |
US20040060685A1 (en) * | 2001-06-11 | 2004-04-01 | Ranjan Ray | Centrifugal casting of titanium alloys with improved surface quality, structural integrity and mechanical properties in isotropic graphite molds under vacuum |
US6799626B2 (en) | 2001-05-15 | 2004-10-05 | Santoku America, Inc. | Castings of metallic alloys with improved surface quality, structural integrity and mechanical properties fabricated in finegrained isotropic graphite molds under vacuum |
US6799627B2 (en) | 2002-06-10 | 2004-10-05 | Santoku America, Inc. | Castings of metallic alloys with improved surface quality, structural integrity and mechanical properties fabricated in titanium carbide coated graphite molds under vacuum |
US20050016706A1 (en) * | 2003-07-23 | 2005-01-27 | Ranjan Ray | Castings of metallic alloys with improved surface quality, structural integrity and mechanical properties fabricated in refractory metals and refractory metal carbides coated graphite molds under vacuum |
-
1963
- 1963-04-03 US US270189A patent/US3265574A/en not_active Expired - Lifetime
- 1963-04-03 FR FR7719A patent/FR2625M/en not_active Expired
Non-Patent Citations (1)
Title |
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None * |
Cited By (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6799626B2 (en) | 2001-05-15 | 2004-10-05 | Santoku America, Inc. | Castings of metallic alloys with improved surface quality, structural integrity and mechanical properties fabricated in finegrained isotropic graphite molds under vacuum |
US6705385B2 (en) | 2001-05-23 | 2004-03-16 | Santoku America, Inc. | Castings of metallic alloys with improved surface quality, structural integrity and mechanical properties fabricated in anisotropic pyrolytic graphite molds under vacuum |
US6634413B2 (en) | 2001-06-11 | 2003-10-21 | Santoku America, Inc. | Centrifugal casting of nickel base superalloys in isotropic graphite molds under vacuum |
US20040060685A1 (en) * | 2001-06-11 | 2004-04-01 | Ranjan Ray | Centrifugal casting of titanium alloys with improved surface quality, structural integrity and mechanical properties in isotropic graphite molds under vacuum |
US6755239B2 (en) | 2001-06-11 | 2004-06-29 | Santoku America, Inc. | Centrifugal casting of titanium alloys with improved surface quality, structural integrity and mechanical properties in isotropic graphite molds under vacuum |
US6776214B2 (en) | 2001-06-11 | 2004-08-17 | Santoku America, Inc. | Centrifugal casting of titanium alloys with improved surface quality, structural integrity and mechanical properties in isotropic graphite molds under vacuum |
US6799627B2 (en) | 2002-06-10 | 2004-10-05 | Santoku America, Inc. | Castings of metallic alloys with improved surface quality, structural integrity and mechanical properties fabricated in titanium carbide coated graphite molds under vacuum |
US20050016706A1 (en) * | 2003-07-23 | 2005-01-27 | Ranjan Ray | Castings of metallic alloys with improved surface quality, structural integrity and mechanical properties fabricated in refractory metals and refractory metal carbides coated graphite molds under vacuum |
US6986381B2 (en) | 2003-07-23 | 2006-01-17 | Santoku America, Inc. | Castings of metallic alloys with improved surface quality, structural integrity and mechanical properties fabricated in refractory metals and refractory metal carbides coated graphite molds under vacuum |
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Publication number | Publication date |
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FR2625M (en) | 1964-06-29 |
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