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N&PD Moderators: Skorpio | someguyontheinternet
amphetamine phosphate bioassay'd
- Thread starter yaesutom
- Start date
I always suspected the phosphates to be superior
Dont forget the special effects of Phosphor it have a cold flame!
Active phosphor have quality of making O3 (Ozone) just like electricity
Ozone is what protecting us from the sheer force of the life etheric sun rays
Im sure phosphor is protecting the human organism
Phosphorlipides are also an important cell substance
Nice work yaesutom ay?
I think we have allot of special considerations, im also a great fan of sacred geometry
Dont forget the special effects of Phosphor it have a cold flame!
Active phosphor have quality of making O3 (Ozone) just like electricity
Ozone is what protecting us from the sheer force of the life etheric sun rays
Im sure phosphor is protecting the human organism
Phosphorlipides are also an important cell substance
Nice work yaesutom ay?
I think we have allot of special considerations, im also a great fan of sacred geometry
What??? Can we get any chem heads or pharmacology people in here lets discuss this..
So here's whats in Adderall:
Well different salts of different drugs seem to absorb at different rates no? I'm sure i could come up with some huge list of drugs on the "legal drug market" with all kinds of different salts for all kinds of different reasons.
There's a huge thread about the "phosphoric acid method" or whatever on ayahuasca.com, something about DMT possibly absorbing better I don't know - but I did get some phosphoric acid and did make some DMT phosphate, and ate it, and it DID seem to not only come on faster but was a lot stronger for the 60 or so milligrams I took (with harmala/line beforehand like usual) - I haven't experimented any more than the one time so i can't really say, but DMT when taken orally does have absorption problems (if you eat fatty food afterwards sometimes it will 'kick in' more DMT) - and i definitely will be experimenting in the future soon as i'm a DMT head and well i love my DMT
.
fastandbulbous
Bluelight Crew
The amphetamine phosphate shouldn't be any different in effects to the amphetamine sulphate, although it may well come on more quickly (due to solubility) and not be nearly as rough (the sulphate ion isn't something you normally find in the human body a lot, whereas the phosphate ion is the main component of bone).
All in all, it's possible that it may feel a bit different (for reasons given above), but in the final analysis, it's tha amphetamine alone doing the CNS stimulation. All different salts can really do is alter the experience to a small degree (the difference between Na and K salts of GHB would be a comparable thing)
All in all, it's possible that it may feel a bit different (for reasons given above), but in the final analysis, it's tha amphetamine alone doing the CNS stimulation. All different salts can really do is alter the experience to a small degree (the difference between Na and K salts of GHB would be a comparable thing)
^^
Yeah there is a definite noticeable difference between taking just GBL and Na-GHB, the sodium salt comes on much slower and lasts longer - but, the feeling is altered also, less of a "drunk" feeling.. well hard to explain, but i've read that K-GHB has a 'different feel' to Na-GHB too, I just got some more GBL I may react some of it with NaOH - I don't have any KOH but if i did i'd make the potassium salt instead (or both). GBL sure comes on fast, but its not as smooth and for some reason just doesn't feel as "clean" as Na-GHB.
Yeah there is a definite noticeable difference between taking just GBL and Na-GHB, the sodium salt comes on much slower and lasts longer - but, the feeling is altered also, less of a "drunk" feeling.. well hard to explain, but i've read that K-GHB has a 'different feel' to Na-GHB too, I just got some more GBL I may react some of it with NaOH - I don't have any KOH but if i did i'd make the potassium salt instead (or both). GBL sure comes on fast, but its not as smooth and for some reason just doesn't feel as "clean" as Na-GHB.
BilZ0r said:
Come on man! Thats subjective! Thats not science!
Some people just dont feel the difference on different drugs
Besides HCl and Sulphate salts are more alike than lets say phosphate!
Please just try before you open your mouth
Every molecyle has its own unique qualities
Not something to discuss, this is a fact, some people are more sensitive than others... Some people can detect more than others, its a matter of subject as well as object, people reacts different to different drugs also
fastandbulbous
Bluelight Crew
No they're not. Sulphate (SO4) and phosphate (PO4) are quite alike as they both come from stong acids that are a result of oxidation of a non metal, followed by its reaction with water to produce the acid; as you can see hydrochloric acid contains no oxygen (oxygen means 'acid producer'). In terms of physical properties, phosphates and sulphates dissociate more in soln (to produce ions) than hydrochloride salts and both phosphates and sulphates have a very low solubility in alcohol (& other organic solvents) for this very reason. Hydrochloride salts can be found to dissolve in a lot of organic solvents
Try & follow your own advice...
You did not understand what i was trying to tell you!
We are talking about different things here
I agree that Sulphur and Phosphorus both have great affinity to warmth/fire
But not in the way that you think
I agree that some of this might be speculation but there are some very important facts one needs to understand
Sulphur burns with a VERY hot flame!!
And is very reactive
Phosphorus light need the creation of
Phosphorus trioxyd
Ozone have not been investigated fully
PHosphoric acid are needed for plants, animals and humans in building protein, look at plant seeds
Try to add 760 mm Hg pressured O2 and looks what heppning to the flame of phosphorus it goes away!
Let me tell you again, its flame are COLD
Sulphur are VERY HOT when ignited
What it is = looks very much like pure light like we know it in the upper atmospheric layer
But this is not what im getting at
Im not saying that what you say isnt true, im just saying that there are other facts that you are not mentioning
We are talking about actual drug induced effect
Its allright with me if you would rather ingest sulphur and chloride than phosphorus
Did you know about the O3 (Ozone) effect and cold flame of Phosphor-
Ozone are absorbing the life etheric rays from the sun
3O2 - 2O3
Look at the bones, the sea shells etc.
If we are to subject it to further investigation we could compare it with 3 other substances found in the earthSilica, LimeCalcium, Clay/Aluminium - Geo-sphere we call it (do not misunderstand this)
And the hydro-sphere
Sulphur, Magnesia, Halogens, Alkalis
Lets then say that CI have a special affinity with earth
But earth and fire are like ending and begining, they are very much a reflection as well as opposites in temperature, BUT DRY is the KEY
look at wikipedia there are some minor information:
From Wikipedia, the free encyclopedia.
A phosphor is a substance that exhibits the phenomenon of phosphorescence (sustained glowing without further stimulus).
The chemical element phosphorus (Greek. phosphoros, meaning "light bearer") was discovered by German alchemist Hennig Brand in 1669 through a Phosphorus, (from the Greek language Phosphoros meaning "light bearing"), is the chemical element in the periodic table that has the symbol P and atomic number 15. A multivalent, nonmetal of the nitrogen group, phosphorus is commonly found in inorganic phosphate rocks and in all living cells. Due to its high reactivity, it is never found as a free element in nature. It emits a faint glow upon exposure to oxygen (hence its name, Latin for 'morning star', from Greek words meaning 'light' and 'bring'), occurs in several allotropic forms, and is an essential element for living organisms. The most important commercial use of phosphorus is in the production of fertilizers. It is also widely used in explosives, friction matches, fireworks, pesticides, toothpaste, and detergents.
We are talking about different things here
I agree that Sulphur and Phosphorus both have great affinity to warmth/fire
But not in the way that you think
I agree that some of this might be speculation but there are some very important facts one needs to understand
Sulphur burns with a VERY hot flame!!
And is very reactive
Phosphorus light need the creation of
Phosphorus trioxyd
Ozone have not been investigated fully
PHosphoric acid are needed for plants, animals and humans in building protein, look at plant seeds
Try to add 760 mm Hg pressured O2 and looks what heppning to the flame of phosphorus it goes away!
Let me tell you again, its flame are COLD
Sulphur are VERY HOT when ignited
What it is = looks very much like pure light like we know it in the upper atmospheric layer
But this is not what im getting at
Im not saying that what you say isnt true, im just saying that there are other facts that you are not mentioning
We are talking about actual drug induced effect
Its allright with me if you would rather ingest sulphur and chloride than phosphorus
Did you know about the O3 (Ozone) effect and cold flame of Phosphor-
Ozone are absorbing the life etheric rays from the sun
3O2 - 2O3
Look at the bones, the sea shells etc.
If we are to subject it to further investigation we could compare it with 3 other substances found in the earthSilica, LimeCalcium, Clay/Aluminium - Geo-sphere we call it (do not misunderstand this)
And the hydro-sphere
Sulphur, Magnesia, Halogens, Alkalis
Lets then say that CI have a special affinity with earth
But earth and fire are like ending and begining, they are very much a reflection as well as opposites in temperature, BUT DRY is the KEY
look at wikipedia there are some minor information:
From Wikipedia, the free encyclopedia.
A phosphor is a substance that exhibits the phenomenon of phosphorescence (sustained glowing without further stimulus).
The chemical element phosphorus (Greek. phosphoros, meaning "light bearer") was discovered by German alchemist Hennig Brand in 1669 through a Phosphorus, (from the Greek language Phosphoros meaning "light bearing"), is the chemical element in the periodic table that has the symbol P and atomic number 15. A multivalent, nonmetal of the nitrogen group, phosphorus is commonly found in inorganic phosphate rocks and in all living cells. Due to its high reactivity, it is never found as a free element in nature. It emits a faint glow upon exposure to oxygen (hence its name, Latin for 'morning star', from Greek words meaning 'light' and 'bring'), occurs in several allotropic forms, and is an essential element for living organisms. The most important commercial use of phosphorus is in the production of fertilizers. It is also widely used in explosives, friction matches, fireworks, pesticides, toothpaste, and detergents.
Last edited:
fastandbulbous
Bluelight Crew
What traps? - I'm a nice person
!After that, I can't see how anything you've written has anything to do with clinical pharmacology/pharmacokinetics. As a matter of fact I don't see what it has to do with anything. It's just a collection of garbled statements that have very little to do with each other and absolutely nothing to do with the difference/similarities between amine salts of sulphuric, phosphoric and hydrochloric acid and how they would effect the pharmacology of the amphetamine salts of these acids
^^ Ok thats fine and dandy but, whats the reason then for, for example Adderall having sulfate, saccarate, aspartate salts, of d or l amphetamine? I thought that played a role in its "time release"? Some of the dexamphetamine hits you right away then some of it just comes on slower/lasts longer (if i'm wrong let me know).
lifeisforliving
Bluelighter
Black said:
I thought that they only partially dissociated or took time to dissociate (which would explain the use of different salts.)....
fastandbulbous
Bluelight Crew
lifeisforliving wins a cupie doll for noticing the difference!
I think the different salts are an attempt to try and stagger the avilability/absorbtion of amphetamine in the gut. I can't see any other reason that makes any sense for having a whole mish-mash of amphetamine salts in one tablet
I think the different salts are an attempt to try and stagger the avilability/absorbtion of amphetamine in the gut. I can't see any other reason that makes any sense for having a whole mish-mash of amphetamine salts in one tablet
C6H6
Bluelighter
- Joined
- Jan 29, 2005
- Messages
- 607
Amantadine is an anti-Parkinson drug. It's a tiny cage of carbons with an amino group sticking out, a beautiful molecule. It's sold as tablets with either the HCl or H2SO4 salt. The HCl salt produces a quick, high spike in the blood level, the H2SO4 salt a more gradual climb with lower peak levels. The reason is that the HCl salt is freely soluble in water, the H2SO4 salt poorly. So different salts can have somewhat different effects if their physical properties are different. But two highly soluble salts will have practically identical effects. So if Amph phosphate has low solubility the effect could be perceived as more 'smooth' because blood levels climb slower and to a lower level. The effect will be prolonged at the cost of intensity. Tannates, salts of tannic acid, and pamoates (from pamoic acid) are very poorly soluble in water and are used as slow release formulations.
Amphetamine Dihydrogen Phosphate
Monobasic Phosphate Of 1-Phenyl-2-Aminopropane
Theodore V. Goggia
United States Patent US2907468
My invention relates to a new chemical compound that is especially suited for therapeutic use. More particularly it concerns the monobasic phosphate of 1-phenyl-2-aminopropane, a method of preparing it, and therapeutic compositions containing this salt.
It is known that 1-phenyl-2-aminopropane (commonly referred to as "amphetamine") and certain of its salts have a pronounced therapeutic effect, particularly as stimulants for the central nervous system. This is evidenced by a feeling of well-being and energy, as well as by a reduction of appetite and desire to sleep. The foregoing effects render these compounds of substantial value in the treatment of various pathologic conditions, such as despondency, fatigue, alcoholism, narcolepsy, obesity and the like. Unfortunately, the beneficial effects of these known compounds are accompanied by certain deleterious effects, particularly an undesirable stimulation of the sympathetic nervous system, frequently resulting in uncontrollable jitteriness. Often a cumulative effect of repeated dosages is evidenced by a disagreeable "hang-over." Furthermore, the known compounds leave much to be desired in one or more respects, such as solubility, stability, metabolism, etc.
It is an object of my invention to provide a novel salt of 1-phenyl-2-aminopropane which possesses the above-mentioned beneficial effects to an unusual extent, and which at the same time possesses the deleterious effects referred to previously to a lesser extent than was heretofore deemed possible. A further object is to provide such a salt having improved physical properties, compared to the known salts. and which is subject to more economical utilization by the body.
Another object is to prepare the new salt in a simple, expeditious manner, whereby a high degree of purity, excellent physical form and great stability are assured. A still further object is to make available various therapeutic compositions particularly adapted for the treatment of obesity and of dysmenorrhea, in which my novel salt is combined with other therapeutically active constituents for maximum desired effect. Additional objects will become apparent from a consideration of the following description and claims.
The foregoing objects are accomplished in accordance with my invention which is particularly concerned with the monobasic phosphate salt of 1-phenyl-2-aminopropane. This novel compound will hereinafter sometimes be referred to as "monobasic amphetamine phosphate" or "amphetamine dihydrogen phosphate." Said salt formed by the combination of equimolecular amounts of the amphetamine base and phosphoric acid. It is distinguished from the dibasic (monohydrogen) and tribasic (fully neutralized) forms, since these contain two and three mots, respectively, of amphetamine for each mol of phosphoric acid. My new salt may be represented by the following structural formula:
The novel amphetamine dihydrogen phosphate may exist in the dextro- or levo- rotary forms or as a racemic mixture thereof, depending upon the form of the base from which it is derived. In practice, I prefer to employ the racemic form and the specific data hereinafter given concerning the physical characteristics of the salt apply to this form of the salt.
My monobasic amphetamine phosphate is a white, impalpable powder that is freely soluble in water and sparingly soluble or insoluble in most organic solvents. It is not demonstrably hygroscopic and is completely stable under ordinary conditions of storage. It begins to sinter at 145°C., becomes a clear amorphous mass without liquefaction at 147°C, and retains the latter form up to about 285°C. at which point it begins to decompose with the evolution of a gas (probably CO2). Its melting point could therefore not be determined.
My new salt may be prepared by adding to amphetamine an equimolecular amount of phosphoric acid. The amount of phosphoric acid required may either be calculated beforehand or else controlled by observing the pH of the reaction mixture and discontinuing the addition as soon as the desired pH value is reached. The pH of a 10% solution of my new salt at a temperature of 25°C is 4.95-5.00 determined colorimetrically and electrometrically. The neutralization reaction is strongly exothermic and, unless modified and controlled in a manner such as will be hereinafter described, results only in a chemical mass consisting of varying proportions of the three possible phosphates with, under certain circumstances, an excess of base or of acid intermingled.
I have found that the necessary control of the reaction may be achieved by having present a substantial amount of a solvent for the amphetamine. One may employ a solution of the amphetamine in water or in an organic solvent such as carbon tetrachloride, ethylene glycol, propyl alcohol, chloroform, acetone and the like. The organic solvents, particularly acetone, are preferred. The phosphoric acid is slowly added to such an amphetamine solution under constant agitation. . After the precise amount required to form the monobasic salt has been added, agitation is continued for up to a half hour or more to insure complete conversion of the base to the desired salt. When an organic solvent such as acetone is employed, the salt separates in the form of a fine, white, flocculent precipitate that becomes more and more dense and abundant as the reaction proceeds. The precipitate may be separated by filtration and, when dried, is in a very suitable form for compounding in various therapeutic preparations.
The following example will serve to illustrate the preparation of my new salt. The invention is, of course, not limited, to the details given therein.
Example
135 grams (1 mol) of amphetamine (1-phenyl-2-aminopropane) were stirred into 300 mL of acetone in a stainless-steel vessel. To the resultant solution there were slowly added under constant agitation 115.3 grams of 85% phosphoric acid (containing 1 mol of H3PO4), care being taken to avoid any sudden rise in temperature or local overheating due to the considerable amount of heat that is evolved. During the addition of the phosphoric acid a fine white, flocculent precipitate appears which becomes more and more dense and abundant, as the quantity of added acid increases.
When the entire quantity of the phosphoric acid has thus been added, agitation of the mixture is continued for about a half hour or more to insure complete conversion. The precipitate is then allowed to settle, the supernatant liquid is drawn off, and the residue is filtered. The precipitate thus separated may, if desired, be washed with acetone and is then dried by evaporation to constant weight. It forms a fine, white, impalpable powder consisting of pure monobasic amphetamine phosphate. When employing the racemic amphetamine, a racemic salt is formed having the physical characteristics hereinbefore described.
My new salt, obtained as described above, may, if desired, be ground to such a fineness that it will pass through a 100 mesh sieve. It is then ready for compounding into various forms and preparations for therapeutic use. For example, it may be incorporated in the customary extenders or excipients, such as milk sugar, and made into tablets, each containing a predetermined dosage of the salt, such as 5 or 10 mg. Another convenient and desirable form for oral administration is obtained by incorporating my new salt in the coating of a standard form of chicle chewing gum. In such case the entire dosage of the salt is preferably incorporated in an intermediate layer of the coating, so that it will be quickly available and yet protected by an outer layer.
An important advantage of my new salt lies in its ready solubility in water. It is about six times as soluble as either the dibasic phosphate or the dibasic sulfate. Thus a quicker and more intense therapeutic action is assured. The action is also less persistent from the standpoint of cumulation that may result in a "hang-over" feeling.
Based upon extensive experience in human therapy, I have determined that the monobasic amphetamine phosphate is more effective, dose for dose, than is the dibasic amphetamine sulfate, which is the best known of the amphetamine salts. This is indeed surprising, because my new salt contains less of the amphetamine base than does an equal quantity of the dibasic sulfate. It follows that the amphetamine is far more potent in the form of the monobasic phosphate, than in the form of the salt most widely used today.
While my salt is more. effective, dose for dose, than the dibasic sulfate, insofar as the desired stimulation of the central nervous system is concerned, it produces less undesirable side-effects attributable to stimulation of the sympathetic nervous system. This may be due to the fact that it contains less of the amphetamine base. However, that does not explain why the desired therapeutic effects are not similarly diminished, but rather substantially enhanced. It appears that the undesirable side-effects are distinct from the desired effects of these salts, insofar as dosage is concerned, and it is probable that the desired effects are favorably influenced by the presence of phosphoric acid. It is well known that phosphates in general are metabolized more readily than are the sulfates which are foreign to the physiologic processes of the body. Regardless of what may be the true explanation, the, fact remains that the desired effects can be produced with my new salt, while greatly diminishing or completely eliminating the undesired effects that were heretofore considered inevitable in the therapeutic use of amphetamine salts.
References Cited
The following references are of record in the file of this patent:
Patents
Patent US2358582 Haffner et al., Aug. 22, 1944
Patent US2361373 Alles, Oct. 31, 1944
Patent AU117996 July 10, 1943
Patent AU119265 Nov. 21, 1944
Other References
Bakas, "Zentralblatt für Gynokologie," vol. 34, pages 1893-1898 (1938 ).
Chinoin, "Klinische Wochenschrift" vol. 13, page 483 (April 1939 ).
Stepan, "Chemical Abstracts," vol. 37, page 3565 (1943).
Torok, "Chemical Abstracts," vol. 32, page 2211 (1938 ).
Degering, "An Outline of Organic Nitrogen Compounds," (Univ. Lithoprinters, 1945) page 304.
Hygiea Medicinsk Tidskrift, Vol. 102, pages 1635-1642 (1940).
Decision of District CL N. J. Septi. 1, 190, 66 USPQ 440,463, 467,469,
Monobasic Phosphate Of 1-Phenyl-2-Aminopropane
Theodore V. Goggia
United States Patent US2907468
My invention relates to a new chemical compound that is especially suited for therapeutic use. More particularly it concerns the monobasic phosphate of 1-phenyl-2-aminopropane, a method of preparing it, and therapeutic compositions containing this salt.
It is known that 1-phenyl-2-aminopropane (commonly referred to as "amphetamine") and certain of its salts have a pronounced therapeutic effect, particularly as stimulants for the central nervous system. This is evidenced by a feeling of well-being and energy, as well as by a reduction of appetite and desire to sleep. The foregoing effects render these compounds of substantial value in the treatment of various pathologic conditions, such as despondency, fatigue, alcoholism, narcolepsy, obesity and the like. Unfortunately, the beneficial effects of these known compounds are accompanied by certain deleterious effects, particularly an undesirable stimulation of the sympathetic nervous system, frequently resulting in uncontrollable jitteriness. Often a cumulative effect of repeated dosages is evidenced by a disagreeable "hang-over." Furthermore, the known compounds leave much to be desired in one or more respects, such as solubility, stability, metabolism, etc.
It is an object of my invention to provide a novel salt of 1-phenyl-2-aminopropane which possesses the above-mentioned beneficial effects to an unusual extent, and which at the same time possesses the deleterious effects referred to previously to a lesser extent than was heretofore deemed possible. A further object is to provide such a salt having improved physical properties, compared to the known salts. and which is subject to more economical utilization by the body.
Another object is to prepare the new salt in a simple, expeditious manner, whereby a high degree of purity, excellent physical form and great stability are assured. A still further object is to make available various therapeutic compositions particularly adapted for the treatment of obesity and of dysmenorrhea, in which my novel salt is combined with other therapeutically active constituents for maximum desired effect. Additional objects will become apparent from a consideration of the following description and claims.
The foregoing objects are accomplished in accordance with my invention which is particularly concerned with the monobasic phosphate salt of 1-phenyl-2-aminopropane. This novel compound will hereinafter sometimes be referred to as "monobasic amphetamine phosphate" or "amphetamine dihydrogen phosphate." Said salt formed by the combination of equimolecular amounts of the amphetamine base and phosphoric acid. It is distinguished from the dibasic (monohydrogen) and tribasic (fully neutralized) forms, since these contain two and three mots, respectively, of amphetamine for each mol of phosphoric acid. My new salt may be represented by the following structural formula:
The novel amphetamine dihydrogen phosphate may exist in the dextro- or levo- rotary forms or as a racemic mixture thereof, depending upon the form of the base from which it is derived. In practice, I prefer to employ the racemic form and the specific data hereinafter given concerning the physical characteristics of the salt apply to this form of the salt.
My monobasic amphetamine phosphate is a white, impalpable powder that is freely soluble in water and sparingly soluble or insoluble in most organic solvents. It is not demonstrably hygroscopic and is completely stable under ordinary conditions of storage. It begins to sinter at 145°C., becomes a clear amorphous mass without liquefaction at 147°C, and retains the latter form up to about 285°C. at which point it begins to decompose with the evolution of a gas (probably CO2). Its melting point could therefore not be determined.
My new salt may be prepared by adding to amphetamine an equimolecular amount of phosphoric acid. The amount of phosphoric acid required may either be calculated beforehand or else controlled by observing the pH of the reaction mixture and discontinuing the addition as soon as the desired pH value is reached. The pH of a 10% solution of my new salt at a temperature of 25°C is 4.95-5.00 determined colorimetrically and electrometrically. The neutralization reaction is strongly exothermic and, unless modified and controlled in a manner such as will be hereinafter described, results only in a chemical mass consisting of varying proportions of the three possible phosphates with, under certain circumstances, an excess of base or of acid intermingled.
I have found that the necessary control of the reaction may be achieved by having present a substantial amount of a solvent for the amphetamine. One may employ a solution of the amphetamine in water or in an organic solvent such as carbon tetrachloride, ethylene glycol, propyl alcohol, chloroform, acetone and the like. The organic solvents, particularly acetone, are preferred. The phosphoric acid is slowly added to such an amphetamine solution under constant agitation. . After the precise amount required to form the monobasic salt has been added, agitation is continued for up to a half hour or more to insure complete conversion of the base to the desired salt. When an organic solvent such as acetone is employed, the salt separates in the form of a fine, white, flocculent precipitate that becomes more and more dense and abundant as the reaction proceeds. The precipitate may be separated by filtration and, when dried, is in a very suitable form for compounding in various therapeutic preparations.
The following example will serve to illustrate the preparation of my new salt. The invention is, of course, not limited, to the details given therein.
Example
135 grams (1 mol) of amphetamine (1-phenyl-2-aminopropane) were stirred into 300 mL of acetone in a stainless-steel vessel. To the resultant solution there were slowly added under constant agitation 115.3 grams of 85% phosphoric acid (containing 1 mol of H3PO4), care being taken to avoid any sudden rise in temperature or local overheating due to the considerable amount of heat that is evolved. During the addition of the phosphoric acid a fine white, flocculent precipitate appears which becomes more and more dense and abundant, as the quantity of added acid increases.
When the entire quantity of the phosphoric acid has thus been added, agitation of the mixture is continued for about a half hour or more to insure complete conversion. The precipitate is then allowed to settle, the supernatant liquid is drawn off, and the residue is filtered. The precipitate thus separated may, if desired, be washed with acetone and is then dried by evaporation to constant weight. It forms a fine, white, impalpable powder consisting of pure monobasic amphetamine phosphate. When employing the racemic amphetamine, a racemic salt is formed having the physical characteristics hereinbefore described.
My new salt, obtained as described above, may, if desired, be ground to such a fineness that it will pass through a 100 mesh sieve. It is then ready for compounding into various forms and preparations for therapeutic use. For example, it may be incorporated in the customary extenders or excipients, such as milk sugar, and made into tablets, each containing a predetermined dosage of the salt, such as 5 or 10 mg. Another convenient and desirable form for oral administration is obtained by incorporating my new salt in the coating of a standard form of chicle chewing gum. In such case the entire dosage of the salt is preferably incorporated in an intermediate layer of the coating, so that it will be quickly available and yet protected by an outer layer.
An important advantage of my new salt lies in its ready solubility in water. It is about six times as soluble as either the dibasic phosphate or the dibasic sulfate. Thus a quicker and more intense therapeutic action is assured. The action is also less persistent from the standpoint of cumulation that may result in a "hang-over" feeling.
Based upon extensive experience in human therapy, I have determined that the monobasic amphetamine phosphate is more effective, dose for dose, than is the dibasic amphetamine sulfate, which is the best known of the amphetamine salts. This is indeed surprising, because my new salt contains less of the amphetamine base than does an equal quantity of the dibasic sulfate. It follows that the amphetamine is far more potent in the form of the monobasic phosphate, than in the form of the salt most widely used today.
While my salt is more. effective, dose for dose, than the dibasic sulfate, insofar as the desired stimulation of the central nervous system is concerned, it produces less undesirable side-effects attributable to stimulation of the sympathetic nervous system. This may be due to the fact that it contains less of the amphetamine base. However, that does not explain why the desired therapeutic effects are not similarly diminished, but rather substantially enhanced. It appears that the undesirable side-effects are distinct from the desired effects of these salts, insofar as dosage is concerned, and it is probable that the desired effects are favorably influenced by the presence of phosphoric acid. It is well known that phosphates in general are metabolized more readily than are the sulfates which are foreign to the physiologic processes of the body. Regardless of what may be the true explanation, the, fact remains that the desired effects can be produced with my new salt, while greatly diminishing or completely eliminating the undesired effects that were heretofore considered inevitable in the therapeutic use of amphetamine salts.
References Cited
The following references are of record in the file of this patent:
Patents
Patent US2358582 Haffner et al., Aug. 22, 1944
Patent US2361373 Alles, Oct. 31, 1944
Patent AU117996 July 10, 1943
Patent AU119265 Nov. 21, 1944
Other References
Bakas, "Zentralblatt für Gynokologie," vol. 34, pages 1893-1898 (1938 ).
Chinoin, "Klinische Wochenschrift" vol. 13, page 483 (April 1939 ).
Stepan, "Chemical Abstracts," vol. 37, page 3565 (1943).
Torok, "Chemical Abstracts," vol. 32, page 2211 (1938 ).
Degering, "An Outline of Organic Nitrogen Compounds," (Univ. Lithoprinters, 1945) page 304.
Hygiea Medicinsk Tidskrift, Vol. 102, pages 1635-1642 (1940).
Decision of District CL N. J. Septi. 1, 190, 66 USPQ 440,463, 467,469,