US2711411A - B-bromotheophylijne salt of z-amino-z- - Google Patents
B-bromotheophylijne salt of z-amino-z- Download PDFInfo
- Publication number
- US2711411A US2711411A US2711411DA US2711411A US 2711411 A US2711411 A US 2711411A US 2711411D A US2711411D A US 2711411DA US 2711411 A US2711411 A US 2711411A
- Authority
- US
- United States
- Prior art keywords
- amino
- salt
- theophylline
- water
- propanol
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 239000011780 sodium chloride Substances 0.000 title description 16
- 150000003839 salts Chemical class 0.000 title description 12
- ZFXYFBGIUFBOJW-UHFFFAOYSA-N Theophylline Chemical compound O=C1N(C)C(=O)N(C)C2=C1NC=N2 ZFXYFBGIUFBOJW-UHFFFAOYSA-N 0.000 description 50
- 239000003814 drug Substances 0.000 description 28
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 28
- 229940079593 drugs Drugs 0.000 description 26
- 229960000278 Theophylline Drugs 0.000 description 22
- 150000001875 compounds Chemical class 0.000 description 22
- 230000001396 anti-anti-diuretic Effects 0.000 description 20
- 230000001882 diuretic Effects 0.000 description 20
- 241000700159 Rattus Species 0.000 description 18
- SKTFQHRVFFOHTQ-UHFFFAOYSA-N 8-bromo-1,3-dimethyl-7H-purine-2,6-dione Chemical compound O=C1N(C)C(=O)N(C)C2=C1NC(Br)=N2 SKTFQHRVFFOHTQ-UHFFFAOYSA-N 0.000 description 12
- 229960003357 pamabrom Drugs 0.000 description 12
- 230000000268 renotropic Effects 0.000 description 12
- JLTCWSBVQSZVLT-CDIPANDDSA-N (2S)-N-[(2S)-6-amino-1-[(2-amino-2-oxoethyl)amino]-1-oxohexan-2-yl]-1-[(4R,7S,10S,13S,16S,19R)-19-amino-7-(2-amino-2-oxoethyl)-10-(3-amino-3-oxopropyl)-13-benzyl-16-[(4-hydroxyphenyl)methyl]-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentazacycloicosan Chemical compound NCCCC[C@@H](C(=O)NCC(N)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H]1NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC=2C=CC(O)=CC=2)NC(=O)[C@@H](N)CSSC1.C([C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CSSC[C@@H](C(N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N1)=O)N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCN=C(N)N)C(=O)NCC(N)=O)C1=CC=CC=C1 JLTCWSBVQSZVLT-CDIPANDDSA-N 0.000 description 10
- 229940072644 Pitressin Drugs 0.000 description 10
- 239000002934 diuretic Substances 0.000 description 10
- 230000036731 Diuretic activity Effects 0.000 description 8
- 206010036618 Premenstrual syndrome Diseases 0.000 description 8
- 229940006004 bromotheophylline Drugs 0.000 description 8
- 201000000484 premenstrual tension Diseases 0.000 description 8
- 210000002700 Urine Anatomy 0.000 description 6
- 150000001412 amines Chemical class 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- BDERNNFJNOPAEC-UHFFFAOYSA-N propanol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 6
- 238000011084 recovery Methods 0.000 description 6
- 239000011734 sodium Substances 0.000 description 6
- 239000008399 tap water Substances 0.000 description 6
- 208000004880 Polyuria Diseases 0.000 description 4
- LRFVTYWOQMYALW-UHFFFAOYSA-N Xanthine Chemical compound O=C1NC(=O)NC2=C1NC=N2 LRFVTYWOQMYALW-UHFFFAOYSA-N 0.000 description 4
- 230000035619 diuresis Effects 0.000 description 4
- 230000003907 kidney function Effects 0.000 description 4
- 230000002175 menstrual Effects 0.000 description 4
- 230000025627 positive regulation of urine volume Effects 0.000 description 4
- KEAYESYHFKHZAL-UHFFFAOYSA-N sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 4
- 229910052708 sodium Inorganic materials 0.000 description 4
- 235000020679 tap water Nutrition 0.000 description 4
- 229940058020 2-amino-2-methyl-1-propanol Drugs 0.000 description 2
- CBTVGIZVANVGBH-UHFFFAOYSA-N Aminomethyl propanol Chemical compound CC(C)(N)CO CBTVGIZVANVGBH-UHFFFAOYSA-N 0.000 description 2
- 229960003556 Aminophylline Drugs 0.000 description 2
- 210000003423 Ankle Anatomy 0.000 description 2
- 206010004053 Bacterial toxaemia Diseases 0.000 description 2
- 241000283690 Bos taurus Species 0.000 description 2
- 239000005977 Ethylene Substances 0.000 description 2
- 206010022998 Irritability Diseases 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- LCCCMFGLBNAGRX-UHFFFAOYSA-N NC(C(O)C)C.N1(C)C(=O)N(C)C=2N=CNC2C1=O Chemical compound NC(C(O)C)C.N1(C)C(=O)N(C)C=2N=CNC2C1=O LCCCMFGLBNAGRX-UHFFFAOYSA-N 0.000 description 2
- 206010029216 Nervousness Diseases 0.000 description 2
- 102100010811 SALL2 Human genes 0.000 description 2
- 101700043774 SALL2 Proteins 0.000 description 2
- 210000003491 Skin Anatomy 0.000 description 2
- 241000019011 Tasa Species 0.000 description 2
- 101710036362 Ten-m Proteins 0.000 description 2
- 206010070863 Toxicity to various agents Diseases 0.000 description 2
- 241000209149 Zea Species 0.000 description 2
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 238000009825 accumulation Methods 0.000 description 2
- 230000002686 anti-diuretic Effects 0.000 description 2
- 239000003160 antidiuretic agent Substances 0.000 description 2
- 230000036528 appetite Effects 0.000 description 2
- 235000019789 appetite Nutrition 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- 235000005822 corn Nutrition 0.000 description 2
- 235000005824 corn Nutrition 0.000 description 2
- 230000000875 corresponding Effects 0.000 description 2
- 230000003247 decreasing Effects 0.000 description 2
- 150000004985 diamines Chemical class 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 210000004914 menses Anatomy 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000006011 modification reaction Methods 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 230000000717 retained Effects 0.000 description 2
- 230000003381 solubilizing Effects 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 230000002522 swelling Effects 0.000 description 2
- 239000002699 waste material Substances 0.000 description 2
- 230000004580 weight loss Effects 0.000 description 2
- 229940075420 xanthine Drugs 0.000 description 2
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
- C07D473/04—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms
- C07D473/06—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms with radicals containing only hydrogen and carbon atoms, attached in position 1 or 3
- C07D473/08—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms with radicals containing only hydrogen and carbon atoms, attached in position 1 or 3 with methyl radicals in positions 1 and 3, e.g. theophylline
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
- A61K31/52—Purines, e.g. adenine
- A61K31/522—Purines, e.g. adenine having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
Definitions
- the present invention relates, to a pharmaceutical compound having enhanced diuretic activity,- and more particularly, totthe compound: 8-bromotheophylline-2 amino-Z-methyl-l-propanol,which is a bromotheophylgline salt of 2-amino-2-methyl-l propanol. "These. compounds have the following'structural formulas:
- the, presentainvention is administered iapp .oxi week ;:b'eforethe Onset of menses rarely E gai ning treatment,
- Sections ('3); (4), (5) and (6) show, respectively, the total sodium (Na), potassium- (K), chloride (Cl), and sodium plus potassium, in milli-eq'uivalent weights, per cage of four rats that was found'in the urine recovered during the 4-hour period.
- Section A shows the results using plain tap water
- Section B shows the results using plain tap water plus the subcutaneous pitressin injection hereinbefore described
- Section C shows the results using plain water plus pitressin as in'Section'B and also using the amounts of the theophylline salt specified
- Section 'D compares with Section C, using in this instance the brornotheophylline saltof the invention instead of the theophylline salt.
- premenstrual tension is a symptomcomplex related to abnormal water storage during the premenstrual period and is essentially a Water toxemia.
- the intensity of these symptoms varies directly as the amount of water retained, and relief of the symptoms accompanies the diuresis.
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Description
Grote, Chattanooga, Tenn., assig'noi's fto The Chat tanooga Medicine Company, Chattanooga, Tenm, a corporation of Tennessee No Drawing.
Serial No. 3 21,498 1 Claim. c1. 260-253 Application November 19, 1952,
' symptomsg i V iproductiof h pr'sent'ai tg ftion; -in-.the-treatment-i e a vpremenstrual,:tension is--;that in mostjpatients 'it; pro The present invention relates, to a pharmaceutical compound having enhanced diuretic activity,- and more particularly, totthe compound: 8-bromotheophylline-2 amino-Z-methyl-l-propanol,which is a bromotheophylgline salt of 2-amino-2-methyl-l propanol. "These. compounds have the following'structural formulas:
I 8-bromotheophylline cH3-N-c =ofH 2-amino-2-methyl-1-propanol i CH3 NH! cq nr -cm-c-wmon 1 been combined withflvarioujs amines for/the purpose of solubilizing'the theophylline in. diuretic compositions Probably the. most commomde'rivatiye ofwthis-Ltypeuis theophylline-ethylene v diamine, xknown aunder theiconl mercial name Aminoph'yllineff.
w are also awarethat s. Patent Ne. i,404,319,
issued July 16, 1946, to Robert S; Shelton, discloses :and
claims the theophyllineisalti-of u2t-methyl-2-amino-l-l propanol, alleging ,thatmthis compoundgis superi or to Aminophylline as: a .therapeuticaage'nt y We .have now found't'hat, if the-theophylline oi this type ,of composition is-replaced :by a -halotheophylline;
particularly 8-bromotheophylline, 'not only is "the solu t of t8-bromotheophylline areg suspended in one l terliof water. "To this suspension are addecl eighty-ninegrams: V
bility of the resulting composition increased,- to a greater:
degree than occurs fromwthe; reaction between theophyl- 1 line and the same amine fcompound, particularly 2-x methyl-Z-amino-l-propanol but 1 the 1 resulting; salt-is fa1 superior as a diuretic compound to thepprevjiously known i n U l temvby t mw t Theremarkably increased diuretic properties;tofhthe 2 1 -1 9 halotheophylline-amine salt "of the 1 present; invention makes it a valuable-therapeutic agent in the relief of pre-} menstrual tension, a v condition upon which previously; 3 known derivatives of theophylline hadlittlepr no efiect.
diuretic compounds containing theophylline; 1;
A large percentage of women, estirnated at 3.010)
V 1-; .T bii'f Q '1" th?f qemolesula I I compoundg has b een formed-consisting oflone'mole bromoth a hylline combined jwith fone mole of g-amino extreme nervousness, swelling of the;ankles jncreased;
appetite, irritability; pelvic: pain, and 1 a feeling of tension. The severity of the-discomfornis:directly comw mensurate with the -ax nount of fluid .accurnulated sort; Pounds o i d-lwomenaw otze ime qm;
3 /2 to 4. pounds during the 7 week "preceding the are almost incapacitated gue to;v th symptoms'from water toxemia-.,- Z v V i The Compound. of the hprese ntq nvven on ly efiicient inthe relic F with premenstrual tension:
Patients to whom the com- -Lt ympt m :tasa t siit menstrual,periodgsi 's-- 5. v I, Ang objectaof the p esent mvention sis oaprovidea sal 2=amino+2-m ethy1 l -propanol, fOI' ause 3 intheire lief premenstrual;- tension without 1 {thev presence-11o side: tions usually associatedjwith -the- Jadmini eQphy lin a The salt. of these two compounds' maysbeScalIed -Z amino-Z-methyl-l-propanol '8 -bromotheophyllinate or turefis" well ifstirred and l if necessary completelsolutiou cow in testing the o ,be fexcreted' as urine overa;=four-h our period.
the, presentainvention is administered iapp .oxi week ;:b'eforethe Onset of menses rarely E gai ning treatment,
.One outstandin erapeu vents waterf accumulation without diuresisygifi the treat ment isastarted: 'earlygenoughgso thattheipatients -have-i no; symptoms ofdwa'tergtoxemia throughon their prettherapeutic product' comprising a .halotheophylline;-salt ofa' organic;.amine,;namely, the 8.-bromotheophylline fo si lne grams .Two hundred" all pared to Qthe or'etical -pro'pa nol accordingto'the"following formula 'c s'r-.CH. ;i cH,-QH q The compound decomposes rrather sharply atv 390. 'C.
i The solubility? j wat'er at; froom temperature exceeds 30 31100 c. to give also'lution'havinga pH otaroun e e 7 mpound ot thevpresent invention for, 1ts"d ur etic1 action, the ffollowing procedure 'wa'si'us edi When .rats are given-tap water perorallyQoh}the-;b'asi' rat, on theaverage' of s-1 00% of the waterso given will 1 f,":in"- j addition' to the watc the rats areeachlgiven' sub- 3 cutaneously /2 unit 'of pit're ssi'n, an anti-diuretic drug, only 42% of. the. .water,..on the average, will he ex: creted. In conducting this test, the drug to be tested is given in a dosage on the basis of 0.1 g. of the product per kilogram'body weight of-the rat and the product isadded inthis proportion to :the water and pitressin. In this way, the anti=pitressin action of each of the various compounds is tested in terms ofthc percent of water recovery from the rats. 1 3 a It was found that the diuretic activity of 8'-bromotheophyllineQemino-Lmethybl propanol was 116-; whereas the diuretic-activity of the corresponding theophylline salt: theophylline-Z-amino-2-methyl-l-propanol was only 66, under the same-test conditions. These results are even more startling when the molar proportions. of theophylline per so are considered since one gram of bromotheophylline is equivalent on this basis to only about gram of theophylline U. S. P.
Amore elaborate series of tests were run substantially as the test hereinbefore described wasrun; and the results obtained are shown on the table (below), wherein column (1) shows the dosage of the theophylline or brornotheophyll-ine used in each test, and column (2) showsthe percentage water recovery calculated-by dividing the total volume of water given to a cage (of 4 rats each, which is the number of rats employed toobtain each test figure on the table) into the volumeof urine collected in the following 4 hours. Columns ('3); (4), (5) and (6) show, respectively, the total sodium (Na), potassium- (K), chloride (Cl), and sodium plus potassium, in milli-eq'uivalent weights, per cage of four rats that was found'in the urine recovered during the 4-hour period. Section A shows the results using plain tap water; Section B shows the results using plain tap water plus the subcutaneous pitressin injection hereinbefore described; Section C shows the results using plain water plus pitressin as in'Section'B and also using the amounts of the theophylline salt specified; and Section 'D compares with Section C, using in this instance the brornotheophylline saltof the invention instead of the theophylline salt.
Table SECTION AWATER I Average H d! D SECTION n wsman. rr'rnussny Average.. 1a 2. 3. 22
SECTION O-WATER, PITRESSIN, THEOPHYLLINE 2-AMINO- -METHYL-1-PROPANOL Averag e 64 1.32 0.69 1.72 2.51.
T ableContinued Z'AMIN O-2-METHYL-l-PROPANOL Col. 1 Colt: Col; 3 001. 4 Col. 5 Col. 6
- I. "TottilMlllieiiulvalent Weight s Percent DoseDrugmgJcc. Water t 1 Recovery p v' K" I 761 Nakand 4.84 5.20 4.85 4.23 6.85 as. 3. 7a 2.02 a. as s. so 122 1. as 1.71 2. 22 3.117 126 14s 1.56 2.06 3.04 122 a. as 1. 4a a. 5.21; 112 3.4a l.58 3.24 I 5.01
- sst 2.10 ass 5.71 as 5.00 2.40 was 2.40 as 4530 2.25 4.18 v 6.55 2187 1.94 2.05 4.81. 118 4. 69 2. 17 4. 4s a as 111 3. rs 2. 0s a. 56 5. as
Average 122 l. 93 1. 80 2. O2 3. 73
39 It will be seen from the table-above that in. each instance,
35 be administered to the rats without introducing considerable toxic symptoms in the'test'animals. it is thus clear that the hromotheophylline'drug gives superior as well as different results, inthat it can'be given in large dosages.
40 Ithas also been found that the instant bromotheophyl- 1 line salt gives a unique physiologicalaction that is-different from the general action characteristic of theophylline drugs. It has been established that the major effect of xanthine drugs, including theophylline, is on the cir- 45 culation, which, in turn, causes increased transport conditions connected with'the waste materials including water and salt. Under appropriate conditions the renal circulation becomes affected, and a diuretic efiect may be obtained; but such action, whether or not directly on the renal cells, is, clearly not the major action of these drugs. 1
In viewof the fact that the increased renal functionresults, if at all in the case of these drugs, from changes inthe generalized transport situation, it follows that the renal action induced is variable, depending uponmany 5 other factors afiecting the'transport situation whichmay divert major transport effects to other areas of the body, such as the skin.
Tests have revealed that both the theophylline and the bromot-heophylline drugs show an increase intotal weight no loss in a test animal, but that with'the theophylline drug tl1eloss'-may- -be extra-renal as'well-asrena}, whereas in the case of'the instant bromotheophylline drug the losses are almost exclusively renal. Extra-renal weight loss, known to befdue largely totranspiration through the 5.3 skin-,is-markediy increased under theophyllineaction in hot weather to such an extent that the renal action may be decreased, or evenmarkedly inhibited, as compared to normal controls. Using-the bromotheophylline drug,
however, this action does not take place, thereby showing p u thatthis drugpossess'es a unique focussin'g or localizing effect upon kidney function. This function is" valuable because it'providesa new standardizing agent for corn parative studies on kidney function. Also, tests show that fin hot weather the salt diuresis effectedby-thebremo- 76 theophylline drug is consistently high (compared to the The diuretic activity of a compound, as measured by 5 the above test, is a good indication of its eifectiveness in the relief of premenstrual tension among human females.
The relief of premenstrual tension by the diuretic compound of the present invention may be' explained when it is appreciated that premenstrual tension is a symptomcomplex related to abnormal water storage during the premenstrual period and is essentially a Water toxemia. The intensity of these symptoms varies directly as the amount of water retained, and relief of the symptoms accompanies the diuresis.
6 It will be understood that modifications and variations may be efiected without departing from the scope of the novel concepts of the-present invention.
We claim'as our invention: 7
The S-bromotheophylline Saltof Z-aminO-Z-rnethyl-I propanol. v p I I 7 References Cited in'the' file of this patent 'UNITED STATES PATENTS 2,576,106 Cusicr Nov; 27, 1951 'oTHER REFERENCES
Publications (1)
Publication Number | Publication Date |
---|---|
US2711411A true US2711411A (en) | 1955-06-21 |
Family
ID=3441080
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US2711411D Expired - Lifetime US2711411A (en) | B-bromotheophylijne salt of z-amino-z- |
Country Status (1)
Country | Link |
---|---|
US (1) | US2711411A (en) |
Cited By (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2994640A (en) * | 1957-02-22 | 1961-08-01 | Byk Gulden Lomberg Chem Fab | Anti-inflammatory therapy with purine molecular compounds |
US5306507A (en) * | 1992-03-26 | 1994-04-26 | Mallinckrodt Specialty Chemicals Company | Process and composition containing pamabrom and pyrilamine maleate |
US20030224006A1 (en) * | 2002-03-01 | 2003-12-04 | Zaworotko Michael J. | Multiple-component solid phases containing at least one active pharmaceutical ingredient |
US20060134198A1 (en) * | 2002-02-15 | 2006-06-22 | Mark Tawa | Pharmaceutical compositions with improved dissolution |
US20070015841A1 (en) * | 2002-02-15 | 2007-01-18 | Transform Pharmaceuticals, Inc. | Pharmaceutical propylene glycol solvate compositions |
US20070059356A1 (en) * | 2002-05-31 | 2007-03-15 | Almarsson Oern | Pharmaceutical co-crystal compositions of drugs such as carbamazepine, celecoxib, olanzapine, itraconazole, topiramate, modafinil, 5-fluorouracil, hydrochlorothiazide, acetaminophen, aspirin, flurbiprofen, phenytoin and ibuprofen |
US20090088443A1 (en) * | 2002-02-15 | 2009-04-02 | Julius Remenar | Novel crystalline forms of conazoles and methods of making and using the same |
US20100279993A1 (en) * | 2002-12-30 | 2010-11-04 | Mark Tawa | Pharmaceutical Propylene Glycol Solvate Compositions |
US20100311701A1 (en) * | 2002-02-15 | 2010-12-09 | Transform Pharmaceuticals, Inc | Pharmaceutical Co-Crystal Compositions |
US7927613B2 (en) | 2002-02-15 | 2011-04-19 | University Of South Florida | Pharmaceutical co-crystal compositions |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2404319A (en) * | 1941-06-28 | 1946-07-16 | Wm S Merrell Co | Butanolamine salts of theophylline |
US2576106A (en) * | 1948-07-13 | 1951-11-27 | Searle & Co | N-dicyclohexyl, dialkylaminoalkanamides |
-
0
- US US2711411D patent/US2711411A/en not_active Expired - Lifetime
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2404319A (en) * | 1941-06-28 | 1946-07-16 | Wm S Merrell Co | Butanolamine salts of theophylline |
US2576106A (en) * | 1948-07-13 | 1951-11-27 | Searle & Co | N-dicyclohexyl, dialkylaminoalkanamides |
Cited By (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2994640A (en) * | 1957-02-22 | 1961-08-01 | Byk Gulden Lomberg Chem Fab | Anti-inflammatory therapy with purine molecular compounds |
US5306507A (en) * | 1992-03-26 | 1994-04-26 | Mallinckrodt Specialty Chemicals Company | Process and composition containing pamabrom and pyrilamine maleate |
US20090088443A1 (en) * | 2002-02-15 | 2009-04-02 | Julius Remenar | Novel crystalline forms of conazoles and methods of making and using the same |
US20060134198A1 (en) * | 2002-02-15 | 2006-06-22 | Mark Tawa | Pharmaceutical compositions with improved dissolution |
US20070015841A1 (en) * | 2002-02-15 | 2007-01-18 | Transform Pharmaceuticals, Inc. | Pharmaceutical propylene glycol solvate compositions |
US7790905B2 (en) | 2002-02-15 | 2010-09-07 | Mcneil-Ppc, Inc. | Pharmaceutical propylene glycol solvate compositions |
US20100311701A1 (en) * | 2002-02-15 | 2010-12-09 | Transform Pharmaceuticals, Inc | Pharmaceutical Co-Crystal Compositions |
US7927613B2 (en) | 2002-02-15 | 2011-04-19 | University Of South Florida | Pharmaceutical co-crystal compositions |
US8362062B2 (en) | 2002-02-15 | 2013-01-29 | Mcneil-Ppc, Inc. | Pharmaceutical compositions with improved dissolution |
US20030224006A1 (en) * | 2002-03-01 | 2003-12-04 | Zaworotko Michael J. | Multiple-component solid phases containing at least one active pharmaceutical ingredient |
US10633344B2 (en) | 2002-03-01 | 2020-04-28 | University Of South Florida | Multiple-component solid phases containing at least one active pharmaceutical ingredient |
US20070059356A1 (en) * | 2002-05-31 | 2007-03-15 | Almarsson Oern | Pharmaceutical co-crystal compositions of drugs such as carbamazepine, celecoxib, olanzapine, itraconazole, topiramate, modafinil, 5-fluorouracil, hydrochlorothiazide, acetaminophen, aspirin, flurbiprofen, phenytoin and ibuprofen |
US20100279993A1 (en) * | 2002-12-30 | 2010-11-04 | Mark Tawa | Pharmaceutical Propylene Glycol Solvate Compositions |
US8183290B2 (en) | 2002-12-30 | 2012-05-22 | Mcneil-Ppc, Inc. | Pharmaceutically acceptable propylene glycol solvate of naproxen |
US8492423B2 (en) | 2002-12-30 | 2013-07-23 | Mcneil-Ppc, Inc. | Pharmaceutical propylene glycol solvate compositions |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US2711411A (en) | B-bromotheophylijne salt of z-amino-z- | |
Nakahara et al. | Toxohormone: a characteristic toxic substance produced by cancer tissue | |
JPS61500359A (en) | Drugs and pharmaceutical compositions for the treatment and/or prevention of skin diseases involving inflammatory processes | |
Hoff-Jørgensen et al. | The effect of phytic acid on the absorption of calcium and phosphorus: 2. In infants | |
Reid | Sea-snake antivenene: successful trial | |
Butterworth et al. | The effects of alpha-and beta-adrenoceptor blocking agents on the responses of the rat uterus to catecholamines throughout the oestrus cycle. | |
US2711409A (en) | Salts of 8-halotheophylline and alkali metal salts of amino acids | |
US3717623A (en) | Sulfanilyl phenyl urea complexes useful against marek's disease | |
US3071508A (en) | Compositions for oral administration in unit dosage form for prophylaxis and treatment of poison ivy and poison sumac dermatitis | |
GB1561524A (en) | Theophylline compositions | |
Wrigley | Glycine in the Treatment of Gout | |
SATO | Studies on the Detoxicating Hormone of the Liver (Yakriton) 39th Report. Effect of Yakriton upon Uranyl Nephritis | |
SIEGEL et al. | Fatal mercurialism due to prolonged intravenous administration of a mercurial diuretic | |
Schultz | Infection of Monkeys With Poliomyelitis Virus by the Gastro-Intestinal Route. | |
Maccordick | A statistical review of 525 cases of lobar pneumonia | |
Aronson | Studies on an Extract of the Kidney | |
DE2448428A1 (en) | DIURETIC AGENTS | |
EP1210949B1 (en) | Lactalbumin for the curative treatment of peptic ulcers | |
Tajima et al. | Thyrotoxic myopathy associated with subacute thyroiditis | |
Madani et al. | Ligation of the bile duct and acute chloroform toxicity in the donkey | |
Hoskins | The functions of the endocrine organs | |
Heller et al. | 4 Diuretic Drugs | |
US2447363A (en) | Compound of urobilinogen and hippuric acid as antipressor | |
Gordon | A Contribution to the Study of Piperazine | |
James et al. | The susceptibility of Schistosoma japonicum in hamsters to metrifonate |