USRE21528E - Amine hydriodides - Google Patents
Amine hydriodides Download PDFInfo
- Publication number
- USRE21528E USRE21528E US RE21528 E USRE21528 E US RE21528E
- Authority
- US
- United States
- Prior art keywords
- salts
- iodine
- hydriodides
- mixture
- ethylene diamine
- Prior art date
Links
- 150000001412 amines Chemical class 0.000 title description 14
- 239000000203 mixture Substances 0.000 description 40
- 150000003839 salts Chemical class 0.000 description 30
- 239000011780 sodium chloride Substances 0.000 description 30
- 239000003814 drug Substances 0.000 description 24
- PIICEJLVQHRZGT-UHFFFAOYSA-N 1,2-ethanediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 22
- 229940012017 Ethylenediamine Drugs 0.000 description 22
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 22
- 229910052740 iodine Inorganic materials 0.000 description 22
- 239000011630 iodine Substances 0.000 description 22
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 20
- 239000002253 acid Substances 0.000 description 10
- 238000000034 method Methods 0.000 description 10
- 239000000243 solution Substances 0.000 description 10
- YAPQBXQYLJRXSA-UHFFFAOYSA-N Theobromine Chemical compound CN1C(=O)NC(=O)C2=C1N=CN2C YAPQBXQYLJRXSA-UHFFFAOYSA-N 0.000 description 8
- 150000001447 alkali salts Chemical class 0.000 description 8
- 238000002425 crystallisation Methods 0.000 description 8
- 230000005712 crystallization Effects 0.000 description 8
- 238000002360 preparation method Methods 0.000 description 8
- 229940032102 ETHYLENEDIAMINE DIHYDRIODIDE Drugs 0.000 description 6
- IWNWLPUNKAYUAW-UHFFFAOYSA-N Ethylenediamine dihydroiodide Chemical compound I.I.NCCN IWNWLPUNKAYUAW-UHFFFAOYSA-N 0.000 description 6
- NLKNQRATVPKPDG-UHFFFAOYSA-M Potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 6
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M Sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 6
- 210000002784 Stomach Anatomy 0.000 description 6
- 206010047700 Vomiting Diseases 0.000 description 6
- 239000007864 aqueous solution Substances 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- OLQIKGSZDTXODA-UHFFFAOYSA-N 4-[3-(4-hydroxy-2-methylphenyl)-1,1-dioxo-2,1$l^{6}-benzoxathiol-3-yl]-3-methylphenol Chemical compound CC1=CC(O)=CC=C1C1(C=2C(=CC(O)=CC=2)C)C2=CC=CC=C2S(=O)(=O)O1 OLQIKGSZDTXODA-UHFFFAOYSA-N 0.000 description 4
- ZBCBWPMODOFKDW-UHFFFAOYSA-N Diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 4
- DDBREPKUVSBGFI-UHFFFAOYSA-N Phenobarbital Chemical compound C=1C=CC=CC=1C1(CC)C(=O)NC(=O)NC1=O DDBREPKUVSBGFI-UHFFFAOYSA-N 0.000 description 4
- 229960002695 Phenobarbital Drugs 0.000 description 4
- 229960004559 Theobromine Drugs 0.000 description 4
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Tris Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 4
- 239000003513 alkali Substances 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 229940079593 drugs Drugs 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- HZAXFHJVJLSVMW-UHFFFAOYSA-N ethanolamine Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 4
- 150000004694 iodide salts Chemical class 0.000 description 4
- 150000002497 iodine compounds Chemical class 0.000 description 4
- 230000003522 irritant Effects 0.000 description 4
- 239000002085 irritant Substances 0.000 description 4
- 231100000021 irritant Toxicity 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 230000004048 modification Effects 0.000 description 4
- 238000006011 modification reaction Methods 0.000 description 4
- 230000001264 neutralization Effects 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 230000001225 therapeutic Effects 0.000 description 4
- 210000001519 tissues Anatomy 0.000 description 4
- FTOAOBMCPZCFFF-UHFFFAOYSA-N Barbital Chemical compound CCC1(CC)C(=O)NC(=O)NC1=O FTOAOBMCPZCFFF-UHFFFAOYSA-N 0.000 description 2
- 229960002319 Barbital Drugs 0.000 description 2
- UDSAIICHUKSCKT-UHFFFAOYSA-N Bromophenol blue Chemical compound C1=C(Br)C(O)=C(Br)C=C1C1(C=2C=C(Br)C(O)=C(Br)C=2)C2=CC=CC=C2S(=O)(=O)O1 UDSAIICHUKSCKT-UHFFFAOYSA-N 0.000 description 2
- LWJROJCJINYWOX-UHFFFAOYSA-L Mercury(II) chloride Chemical compound Cl[Hg]Cl LWJROJCJINYWOX-UHFFFAOYSA-L 0.000 description 2
- YFDLHELOZYVNJE-UHFFFAOYSA-L Mercury(II) iodide Chemical compound I[Hg]I YFDLHELOZYVNJE-UHFFFAOYSA-L 0.000 description 2
- 206010028813 Nausea Diseases 0.000 description 2
- 208000006379 Syphilis Diseases 0.000 description 2
- 229930013930 alkaloids Natural products 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000036772 blood pressure Effects 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 230000000875 corresponding Effects 0.000 description 2
- 230000003247 decreasing Effects 0.000 description 2
- 230000003292 diminished Effects 0.000 description 2
- 235000019441 ethanol Nutrition 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 238000005755 formation reaction Methods 0.000 description 2
- XMBWDFGMSWQBCA-UHFFFAOYSA-M iodide Chemical compound [I-] XMBWDFGMSWQBCA-UHFFFAOYSA-M 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 229960002523 mercuric chloride Drugs 0.000 description 2
- 229960003671 mercuric iodide Drugs 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 239000012452 mother liquor Substances 0.000 description 2
- -1 or in Substances 0.000 description 2
- 230000002035 prolonged Effects 0.000 description 2
- 229930002161 purine alkaloids Natural products 0.000 description 2
- 150000003212 purines Chemical class 0.000 description 2
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 230000001624 sedative Effects 0.000 description 2
- 239000000932 sedative agent Substances 0.000 description 2
- 235000009518 sodium iodide Nutrition 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000005507 spraying Methods 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 230000002195 synergetic Effects 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 238000004448 titration Methods 0.000 description 2
- 230000002588 toxic Effects 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 235000013311 vegetables Nutrition 0.000 description 2
Definitions
- This invention relates to iodine compounds suitable for use in internal medication.
- the chief object of this invention is to produce an iodine compound which is not dangerous 5 to produce, which is not dangerous in its use and which is stable to light and air.
- the chief feature of the invention consists in amine hydriodides in pure form.
- iodine in internal med- 10 ication is well known.
- Alkali salts of hydriodic acid such as sodium and potassium iodide, have been commonly used for internal medication.
- the salts are solid and in order to obtain the desired internal medication efiect, large dosages 15 are usually necessary.
- the material is usually given as tablets.
- the salts are objectionable because of their irritant action on the stomach. With the large dosages usually necessary, the salts may cause nausea and vomiting.
- the medical profession perforce has been restricted thereto unless hydriodic acid has been used.
- Hydriodic acid it is well known, appears to 25 give better medication results than these salts. However, due to the fact that this acid will burn the mucous tissues if administered, the same must be diluted. This requires large dosages to secure the desired iodine medication efiect. Usuao ally when this liquid is used, it is administered as a syrup to minimize the burning efiect before mentioned.
- either or both may be used in combination with alkaloids of the purine group, such as theobromine, with 50 purine alkaloids and sedative drugs of the barbital type, such as pheno-barbital, with the-salicylates, with or without vegetable drugs, or in ,combinations like the so-called mixed treatment formula for syphilis in which the new hy- 55 driodide would be treated with mercuric bichloride to give the corresponding soluble complex mercuric iodide.
- alkaloids of the purine group such as theobromine
- 50 purine alkaloids and sedative drugs of the barbital type such as pheno-barbital
- the-salicylates with or without vegetable drugs
- the amine most suitable for forming such a salt or salts is ethylene diamine.
- a convenient method of preparing these salts is by mixing suitable molecular quantities of the concentrated aqueous solutions of ethylene diamine and hydriodic acid commercially available. Reaction occurs immediately, The desired salts will be readily obtained by concentrating the mixture on a water bath until crystallization takes place. The crystals are then filtered, Washed thoroughly and then dried. The product is then usually pure enough for immediate use. If and when necessary, the product can be further purified by recrystallization from various solvents. A mixture of ethyl alcohol and water is especially suitable for this purpose.
- the quantities of the reagents to be used may be calculated from. their strengths, if known.
- an indicator may be used to determine when the mixture has reached the proper degree of acidity. If, for instance, the mixture is neutral to meta cresol purple or bromphenol blue, the product obtained on crystallization is the pure dihydriodide. If, however, the mixture is less acid, a mixture of the two salts, before mentioned, will be obtained, the proportion of monohydriodide increasing with decreasing acidity until finally when the acidity is suitable, the monohydriodlde is obtained as pure crystals.
- the mixture was then cooled and allowed to crystallize. This resulted in the formation of relatively large size crystals. If the mixture is stirred during the cooling, the size of the crystals will be materially reduced. For tablet preparation, the latter procedure is preferred.
- the crystals were then removed by filtration, washed thoroughly with alcohol and dried. Analysis of a sample of the crystals showed the iodine content thereof to be 80.1%. The theoretically calculated content is 80.37%.
- reagents may be used in the pure state, since both are liquids, or they may be used in other thanaqueous solutionsthat is, in solutions which are not inimical to each other or to the resulting product or subsequent procedure.
- concentration and crystallization may be accomplished by other procedure than that specified.
- concentration and crystallization for example, which is alternative in character, may be as by spraying the solution into a heated current of air. Any number of variations of the procedure hereinbefore specified by way of example, will readily suggest themselves to persons skilled in this art.
Description
Reissued Aug. 13, 1940 ABIINE HYDRIODIDES Frank B. Fisk, Indianapolis, Ind., assignor, by mesne assignments, to AlliedLahoratories, Inc, Kansas City, Mo., a corporation of-Delaware No Drawing. Original No. 2,128,741, dated August 30, 1938, Serial No. 119,271, January 6, 1937. Application for reissue November 4, 1939, Se-
rial No. 302,857
4 Claims.
This invention relates to iodine compounds suitable for use in internal medication.
The chief object of this invention is to produce an iodine compound which is not dangerous 5 to produce, which is not dangerous in its use and which is stable to light and air.
The chief feature of the invention consists in amine hydriodides in pure form.
The administration of iodine in internal med- 10 ication is well known. Alkali salts of hydriodic acid, such as sodium and potassium iodide, have been commonly used for internal medication. The salts are solid and in order to obtain the desired internal medication efiect, large dosages 15 are usually necessary. The material is usually given as tablets. The salts are objectionable because of their irritant action on the stomach. With the large dosages usually necessary, the salts may cause nausea and vomiting. In the 20 absence of any better vehicle for supplying iodine for interal medication, the medical profession perforce has been restricted thereto unless hydriodic acid has been used.
Hydriodic acid, it is well known, appears to 25 give better medication results than these salts. However, due to the fact that this acid will burn the mucous tissues if administered, the same must be diluted. This requires large dosages to secure the desired iodine medication efiect. Usuao ally when this liquid is used, it is administered as a syrup to minimize the burning efiect before mentioned.
There has been prepared the hydriodides of ethylene diamine. Two forms have been pro- 35 duced, to-wit, the dihydriodide and the monohydriodide and either is satisfactory for the administration for internal medication purposes. Either or both may be safely prepared. Either or both are readily soluble each being a white crystal, Each is stable to light and air. Each contains an amount of iodine comparable to the amounts contained in the alkali iodides. Each of these products when administered, does not cause nausea or vomiting, does not burn the mucous tissues and may be readily added to various pharmaceutical combinations for synergistic effect in varying dosage. For example, either or both may be used in combination with alkaloids of the purine group, such as theobromine, with 50 purine alkaloids and sedative drugs of the barbital type, such as pheno-barbital, with the-salicylates, with or without vegetable drugs, or in ,combinations like the so-called mixed treatment formula for syphilis in which the new hy- 55 driodide would be treated with mercuric bichloride to give the corresponding soluble complex mercuric iodide.
The foregoing are set forth as examples of the use of either or both of these products. A number of other such possible combinations will 5 readily suggest themselves to persons skilled in this art and such combinations are possible because these products contain iodine in inorganic combination and in amounts comparable to those found in the alkali salts and are readily soluble in water and other media. When administered directly in solution, their taste may be readily disguised. Briefly stated, therefore, either or both of these compounds possess all the desirable therapeutic features of hydriodic acid but are in solid. form and avoid the administration of the free acid with its attendant disadvantages, and they possess the desirable therapeutic features of the alkali salts of hydriodic acid without the attendant irritant action on the stomach or the accompanying nausea and vomiting. Likewise, comparable to alkali salts of hydriodic acid they are entirely stable to light and air.
The two salts have these formu1as:
NHaCHzCHzNHaHI and HI.NH2CH2CH2NH2.HI
While both salts are quite satisfactory, as previously stated, as medicaments, the latter contains a somewhat greater proportion of iodine in the ratio of 81% as compared with 68%, and accordingly, is more desirable for the administration of iodine since smaller doses thereof will be required to produce a like iodine effect. From the formula before mentioned, it is apparent that one includes but one and the other includes two molecules of the acid.
The amine most suitable for forming such a salt or salts, is ethylene diamine.
A convenient method of preparing these salts by way of illustration only, is by mixing suitable molecular quantities of the concentrated aqueous solutions of ethylene diamine and hydriodic acid commercially available. Reaction occurs immediately, The desired salts will be readily obtained by concentrating the mixture on a water bath until crystallization takes place. The crystals are then filtered, Washed thoroughly and then dried. The product is then usually pure enough for immediate use. If and when necessary, the product can be further purified by recrystallization from various solvents. A mixture of ethyl alcohol and water is especially suitable for this purpose.
The quantities of the reagents to be used may be calculated from. their strengths, if known.
When their strengths are unknown, an indicator may be used to determine when the mixture has reached the proper degree of acidity. If, for instance, the mixture is neutral to meta cresol purple or bromphenol blue, the product obtained on crystallization is the pure dihydriodide. If, however, the mixture is less acid, a mixture of the two salts, before mentioned, will be obtained, the proportion of monohydriodide increasing with decreasing acidity until finally when the acidity is suitable, the monohydriodlde is obtained as pure crystals.
From the foregoing, therefore, it is evident that either salt may be obtained in pure form or any predetermined mixture of these salts may be obtained.
By way of illustration only, the following example of the preparation of the dihydriodide will now be given. To lbs. of an aqueous solution of hydriodic acid (about 62.5%) was added gradually with stirring, 9 lbs. 2 oz. of an aqueous solution of ethylene diamine (about 70%). To this mixture was added the mother liquor from a previous similar lot. Titration of a sample of the mixture, using metacresol purple as an indicator, then showed 5 lbs. of hydriodic acid must be added to render the whole solution neutral to this indicator. When this amount of acid was added to the mixture, the same was heated on the water bath until a crystal crust over the surface of the solution or a pellicle was formed. The mixture was then cooled and allowed to crystallize. This resulted in the formation of relatively large size crystals. If the mixture is stirred during the cooling, the size of the crystals will be materially reduced. For tablet preparation, the latter procedure is preferred. The crystals were then removed by filtration, washed thoroughly with alcohol and dried. Analysis of a sample of the crystals showed the iodine content thereof to be 80.1%. The theoretically calculated content is 80.37%.
It is, of course, to be understood that the details of preparation may vary considerably without essentially altering the basic process. For instance, either or both of the reagents may be used in the pure state, since both are liquids, or they may be used in other thanaqueous solutionsthat is, in solutions which are not inimical to each other or to the resulting product or subsequent procedure.
Also, it is to be understood that concentration and crystallization may be accomplished by other procedure than that specified. Such a concentration and crystallization, for example, which is alternative in character, may be as by spraying the solution into a heated current of air. Any number of variations of the procedure hereinbefore specified by way of example, will readily suggest themselves to persons skilled in this art.
In addition to the hydriodides of ethylene diamine, before mentioned, there has been prerestrictive in character.
pared andstudied the hydriodides of monoethanolamine, diethanolamine and triethanolamine. These resemble very closely the salts of ethylene diamine in appearance, properties and method of where a: is an integer not greater than 3.
From. these results, therefore, it is to be expected that amine hydriodides as a class will give similar excellent results in iodine medication. However, allowance must be made for the individual physiological action of the different amines used. For example, the gradual lowering of the blood pressure produced by ethylene diamine is frequently advantageous. Also the harmful physiological actions of some of the other amines might prevent their use in particular instances. The selection of ethylene diamine, monoethanolamine, diethanolamine and triethanolamine has been intentional, solely because each of the same is less toxic than other well known readily available amines.
With reference to the salts initially mentioned hereinbefore, it may be said that clinical results with a combination of theobromine, phenobarbital and ethylene diamine dihydriodide demonstrate that, by the use of this particular iodide, not only is satisfactory iodine action or medication secured without stomach irritation but the effect thereof is more prolonged than with the use of the ordinary alkali iodides so that the frequency and/or size of the doses (for example, tablets) may be diminished.
While the invention has been described in great detail in the foregoing specifications, the same is to be considered as illustrative and not Various modifications of the method of preparation of the compounds prepared will readily suggest. themselves to persons skilled in this art and the same as well as the modifications hereinbefore mentioned specifically, are all considered to be within the broad scope of the invention, reference being had to the appended claims.
The invention claimed is:
1. Ethylene diamine monohydriodide.
2. Ethylene diamine dihydriodide.
3. A mixture of ethylene diamine monohydriodide and ethylene diamine dihydriodide.
4. A hydriodide of ethylenediamine.
FRANK B. FISK.
Family
ID=
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US3174901A (en) | Process for the oral treatment of diabetes | |
US3634583A (en) | Pharmaceutical composition for the treatment of oedematous conditions and hypertension | |
US2950309A (en) | Amphetamine tannate | |
US2957806A (en) | Process for raising blood serum iron levels and controlling anemia | |
SE7707462L (en) | PROCEDURE FOR PREPARING PENICILLANIC ACID DERIVATIVES | |
JPS6323888A (en) | Oxaazaphosphorine solution and manufacture | |
US2128741A (en) | Amine hydriodides | |
JPS60190742A (en) | Phenylmethylphenoxy compound, manufacture and medicinal composition | |
US3794722A (en) | Iron composition for treating anemia | |
USRE21528E (en) | Amine hydriodides | |
US2851394A (en) | Compositions containing ferrous sulfate and dioctyl sodium sulfosuccinate | |
US3168438A (en) | Vasodilation by nitric acid ester derivatives of nicotinic acid | |
US2144552A (en) | Alkanol-amine salt of mandelic acid | |
US3143469A (en) | Anti-cholesterol nicotinic acid nu-oxide | |
US2165470A (en) | Amine salt preparations for internal medication | |
US3396193A (en) | Halogenated cis-cinnamic acids | |
US2224256A (en) | Pharmaceutical preparation | |
US2449041A (en) | Riboflavin solutions | |
EP0308665B1 (en) | 5-aminosalicylic acid salts and pharmaceutical preparations containing them | |
US3422191A (en) | Compositions and methods for tranquilization employing salts of n-morpholine ethanol | |
US1741761A (en) | Quinine compound and process of making the same | |
US1582940A (en) | Silver-protein preparation | |
US2352012A (en) | Sulphanilamide addition compound | |
US2140461A (en) | Cyclohexylammonium mandelate | |
US3274055A (en) | Acid addition salts of morpholine ethanol |