US 2618584 A
Description (OCR text may contain errors)
Patented Nov. 18, 1952 UNITED STATES PATENT OFFICE DICHLORAMINE COMPOUND SOLUTION No Drawing. Application March 20,1942, Serial No. 435,580
13 Claims. 1
Our invention relates to certain improvements in compositions of matter including compounds containing active-, that is, oxidizing-, chlorine organically bound, especially chlorin attached to nitrogen in an organic amide or similar nitrogenous compound, and in which the chlorine is capable of reacting in an iodide solution to liberate free iodine, or in solution, is capable of oxidizing such compounds as -sulfite, -thiosu1phate, etc.
These organic compounds bearing active chlorine present certain difficulties when it is desired to use them in solutions in organic solvents. Whereas, chloramine T, or rather-its sodium salt, sometimes known as chlorazene, is soluble in water and reasonably stable in aqueous solution, the dichloraminecompounds are-in most instances insoluble in water, but soluble in organic solvents. These solutions are reasonably stable if the solvent is resistant to reaction with chlorine like carbon tetrachloride; but where the solvent can be readily chlorinated, the solution is unstable, reaction readily occurring between the active chlorinating agent and the solvent in which it is dissolved. For use in medicine such solvents as carbon tetrachloride and/or chloroform are not suitable due to high volatility, toxicity and factors of a similar nature. It has been desirable,
nevertheless, to utilize such a solution in nonvolatile and non-toxic solvents and in the past the general practice has been to dissolve such compounds in highly chlorinated solvents; for example, dichloramine T in chlorcosane has been used since the World War I as a treatment for flushing and cleansing wounds, chlorcosane, being difficultly chlorinated and yeta fair solvent for dichloramine T and similar types of products, has been the most generally useable solvent. It is fairly well-known that alcohols and acids are incompatible with these chlorinated products and that aside from chlorcosane (chlorinated paraffin oil) and chlorinated eucalyptol, few other organic solvents were satisfactory.
We have discovered that among the very large number of esters a certain small group are unusually resistant to chlorination by such compounds, are unusually effective as solvents and, being substantially non-volatile as well as substantially watereinsoluble, these products are exceptionally effective solvent for active chlorine-containing compounds. The group which we have found to have the properties we desire are the esters mainly derived from hydroxy acids, such as glycolic acid, or polycarboxy acids such as succinic acid, but we have found that even effective is acetyl triethyl citrate.
more desirable are the esters of hydroxy-polycarboxy acid, such as for example, citric acid. These acids are preferably completely esterified by alkyl acylation of the hydroxy group and alkylation of the carboxy group. The preferred alkyl acyl group is acetyl although We have found straight chain monobasic acyl groups to lauric acid (-C-12) are effective. The preferred alkylation group is ethyl although we have found that straight chain monohydroxy alcohols to the lauryl alcohol (C-12) are effective. In other words, the ester of citric acid (hydroxytricarballylic acid) which we have found most Where the straight chain groups are employed, the structural formula for completely esterified citric acid is Where R1 is monobasic acyl group having a maximum of 12 carbon atom and R2 is an alkyl group having a maximum of 12 carbon atoms. Other common representatives besides citric acid, which we have found effective are, malic acid, tartaric acid, particularly when they are completely esterified with short straight chain aliphatic alcohols and aliphatic acids having within the range of 1 to 12 carbon atoms in the molecule, etc. Among these are esters of glycolic acid, esters of tartaric acid, esters of citric acid, and in particular, diacetyl diethyl tartarate, acetyl ethyl glycolate, acetyl triethyl citrate, etc. The esters of citric acid are particularly suitable and with these we shall group also the corresponding esters of carballylic acid such as triethyl carballylate.
Our preferred esters are excellent solvents for those active chlor-compounds which are not generally insoluble in all normally stable organic solvents. We refer to such active chlor compounds as dichloramine T, the toluene derivatives; benzene sulfonarn-ide dichloride and parachlorobenzone sulphona'mide dichloride, and related aromatic derivatives; to azochloramide and to various other chloramides and dichloramides in which the chlorine attached to the nitrogen is active, i. e. positive.
These preferred esters, are excellent solvents for other chlorine free organic compounds fairly stable to chlorination; for example, the fully esterified derivatives of cellulose, such as cellulose acetate and mixed esters such as cellulose acetate propionate and cellulose acetate butyrate, having the formula CnHZnOZ wherein n lies within the range of 2 and 4, as well as the saturated esters formed from cellulose and acid from the group acetic, propionic and butyric. These esters can be used as thickening agents for the solution whether the solution is used for treating wounds or for other purposes.
An advantage to be noted in the use of the thickened preparations in the treatment of Wounds and other moist surfaces is that whereas with some esters more hydrophilic in character than these, the water tends to dissolve and precipitate the thickening agent, with the citric acid derivatives in particularfor example the acetyl triethyl citratethe product penetrates without precipitation of the thickener through the surface water on the skin or Wound wetting the underlying surface in spite of the presence of this moisture.
The chlorinating compound may range from a small fraction of a percent to a super-saturated solution-or the solution may be actually saturated with the excess (above saturation) of chlorinating compound dispersed in the solvent. Usually the percentage will be in the range as given in the following example:
Parts (1) Ester 75-99 Chlorinating compound 25- 1 or that of a thickened solution would be:
Parts (2) Ester 72-83 Chlorinating compound 25- 1 Thickener 3-11 A specific example of our preferred formula under (1) would be:
Parts (3) Acetyl triethyl citrate 90 Dichloramine 'I' 10 and of a thickened solution would be:
Parts (4) Acetyl triethyl citrate 90 Cellulose acetate butyrate 5 Dichloramine T These esters may be used alone as solvents or may be used mixed with other more water soluble types, or more hydrophilic types such as the glycol or glycerol esters, in order to obtain the desired water acceptance or repellance.
In the case of more water soluble types that have been thickened as for example with cellulose esters, if one attempts to wash away as from skin or fabric such a mixture with Water and soap, the water tends to leach out the solvent leaving the cellulose ester as a very adherent fibrous sort of material. In the case of those esters which are little, if any, water soluble, this does not occur, the solution acting as an oil capable of emulsification in soapy water.
In order to reduce tackiness of such thickened solutions, it is desirable to utilize those solvents with high viscosity, for example acetyl triethyl citrate. Such solutions are not particularly sticky due to the low content of plastic and can be cleaned off by emulsification from surfaces on which they are applied.
The examples given are by way of illustration and not by way of limitation. It will be evident that many changes may be made without departing from the spirit and scope of our invention.
1. A solution of a dichloramine compound dissolved in a saturated ester derived from completely esterified citric acid, having the general formula where R1 is monobasic acyl group having a maximum of 12 carbon atoms and R2 is an alkyl group having a maximum of 12 carbon atoms, said dichloramine compound containing active chlorine wherein the chlorine atom is attached to a, nitrogen atom.
2. A solution of dichloramine T in acetyl triethyl citrate.
3. A solution of benzene sulfonamide dichloride in acetyl triethyl citrate.
4. A solution of azochloramide in acetyl triethyl citrate.
5. A solution of a chloro compound selected from the group consisting of dichloramine T, benzene sulfonamide dichloride, chlorobenzene sulfonamide and azochloramide in acetyl triethyl citrate.
6. A solution of a dichloramine compound containing active chlorine wherein chlorine is attached to nitrogen dissolved in a saturated ester derived from an organic acid selected from the group consisting of glycolic, malic, citric and tartaric acid, the hydroxyl group of said acid being acylated with straight chain monobasic acids containing 1 to 12 carbon atoms and the carboxyl groups being esterified with straight chain aliphatic alcohols having a maximum of 12 carbon atoms.
7. A solution according to claim 6 including also a saturated ester formed from cellulose and a straight chain hydrocarbon aliphatic acid having type formula CnH2nO2 wherein n is a whole number from 2 to 4.
8. A solution according to claim 6 consisting of also a saturated ester formed of cellulose and an acid from the group consisting of acetic, propionic and butyric.
9. A solution according to claim 6, in said acid the hydroxy grou being acetylated and the carboxy acid groups being ethylated.
10. A solution according to claim 6 the propor tion of ester being -99 parts, the proportion of dichloramine compound being 25-1 parts.
11. A solution according to claim 6 the proportion of ester being 72-88 parts, the proportion of dichloramine compound being 25-1 parts, a saturated ester formed of a cellulose and a straight chain hydrocarbon aliphatic acid having type formula CnHZnOZ wherein n is a whole number from 2 to 4, 3-11 parts.
6 12'. A solution of an organic compound includ- REFERENCES CITED ing:
Parts The following references are of record in the Acetyl triethyl citrate 90 file of thls Patent:
hl P mamme T 10 UNITED STATES PATENTS 13. A solution of an organic compound including: Number Name Date Parts 1,927,295 Powers Sept. 19, 1933 Acetyl triethyl citrate 90 10 2,221,139 Hiatt Nov. 12, 1940 fiiiiii fimiffiiEFfffffiijijjjjj:3331:: 13 OTHER REFERENCES RALPH L, EVANS The Extra Pharmacopoeia, v01. 1 (1941). page EVERETT G. MCDONO-UGH. 396.