US2866735A - Therapeutic composition of matter - Google Patents
Therapeutic composition of matter Download PDFInfo
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- US2866735A US2866735A US417214A US41721454A US2866735A US 2866735 A US2866735 A US 2866735A US 417214 A US417214 A US 417214A US 41721454 A US41721454 A US 41721454A US 2866735 A US2866735 A US 2866735A
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- erythromycin
- sulfonamides
- therapeutic composition
- tablet
- sulfadiazine
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
Definitions
- This invention relates to a combination of antibacterial substances, and more particularly relates to the combination of erythromycin and the sulfonamides.
- This invention relates to a combination of antibacterial substances, and more particularly relates to the combination of erythromycin and the sulfonamides.
- the medical art is in constant search of new and better antibacterial substances and combinations thereof. Since bacteria develop resistant strains to the commonly used antibacterial agents and since patients develop sensitivities to antibacterial agents which are used too often, the search for new agents is a continuing and ceaseless struggle for the medical art. Most combinations of antibacterial agents provide little advantage over the individual antibacterial agents used alone. Occasionally, an unusually good combination is discovered.
- Still another object is to provide novel antibacterial preparations which are well tolerated and have negligible allergenic properties. Still another object is to provide such preparations which contain a combination of several sulfonamides in order to minimize possibility of crystalluria renal damage and lessen the incidence of allergic reactions. Other objects will be apparent to those skilled in the art to which this invention pertains.
- the novel composition of the present invention consists of erythromycin and three sulfonamides, the most preferred sulfonamides being snlfadiazine, sulfamerazine, and sulfamethazine.
- the present invention consists in the unexpected properties attributable to the combination of erythromycin with the sulfonamides. The antibacterial advantages of the combination have been clearly demonstrated for erythromycin with one sulfonamide drug, e.
- erythromycin is used herein in its generic sense and denotes erythromycin itself, which is characterized as a nitrogenous base, erythromycin B, and the acid addition salts and esters thereof. It is more fully described in U. S. Patent 2,653,899, issued on September 29, 1953 and Pettinga et al. J. A. C. S. 76: 569-571 1954).
- sulfonamide drug includes sulfanilamide and the various sulfanilamide derivatives involving replacement of a hydrogen atom on the amino and/or amido groups by another group; for example, sulfamethazine, sulfacetamide, sulfamerazine, sulfadiazine, sulfadimetine, sulfisoxizole, sulfaguanidine, sulfapyridine, sulfathiazole, and phthalylsulfathiazole, succinylsulfathiazole, and the like.
- erythromycin and the triple sulfonamides are separated by preparation of a single enteric coated compressed tablet containing erythromycin and laminating it with the triple sulfonamides.
- the triple sulfonamides are rolled onto the enteric coated erythromycin tablet as in conventional pill making. Color coats and polish are applied.
- enteric coated erythromycin core will resist the attack of 3 artificial gastric juice for at least two hours but will disintegrate upon transfer to an alkaline buffer solution of pH 6.8 or artificial intestinal juice (pH 6.9) within one hour.
- an alkaline buffer solution of pH 6.8 or artificial intestinal juice (pH 6.9) within one hour.
- the disintegration time in the. alkaline buffer solution is more in the order. of fifteen .to thirty minutes.
- Another method of preparing an oral preparation having the same characteristics as the above consists of preparing an enteric coated compressed tablet or pill containing the erythromyein, placing it into a hard gelatin capsule, and powder filling the triple sulfonamides.
- Thc compressed tablet used here should be relatively small as compared to the compressed tablet of erythromycin described above; e. g. a one-quarter inchpunch as compared with a three-eighth inchpunch for the laminated tablet.
- the cellulose acetate phthalate coating is applied as previously described and the tablets or tablet inserts, as they are often called, are dried overnight.
- the gelatin capsule dissolves in the stomach exposing the sulfonamides to the action of the stomach juices.
- the enteric coated erythromyein is impervious to the hydrochloric acid in the stomach and remains unchanged until it passes into the intestinal tract where the erythromyein tablet or pill readily disintegrates.
- This tablet insert should have the disintegration specifications previously outlined.
- liquid oral preparations it is preferred to use relatively insoluble esters and salts of erythromycin since these have a lesser tendency to be inactivated by the acid in the stomach, and they are usually more palatable. Even the free base of erythromyein could be used in such liquid oral preparations since the acid in the stomach does not prevent the attainment of thera Therapeutic levels, but this is not the most preferable form by this means of administration.
- insoluble esters preferred in liquid oral preparations are the stearate, cyclopentylpropionate, laureate and the ethyl car bonate.
- An illustrative salt which is also so useful is the stearic acid salt. Any of the conventional liquid vehicles used in pharmaceutical practice which are not incompatible with the active ingredients .of the novel composition of the present invention can be used to prepare the liquid oral embodiment thereof.
- Oil suspensions of the novel composition of the present invention can also be prepared.
- taste is an important factor.
- a soluble ester of erythromycin, i. e., the glutarate, has been found to be most useful in reducing the bitter taste of the free base.
- One example of such an oil suspension contains the following active ingredients for each five cubic centimeters of finished product:
- composition of the present invention can also be prepared as granules, especially for pediatric purposes. These granules can be dissolved in water or dispersed in foods immediately prior to use. These granules are generally prepared in packets containing a single dose.
- a typical pediatric formula contains the following amounts of active material as sugar coated granules:
- composition of the present invention can be prepared in a sterile vehicle for parenteral use, although this is not the preferred form of administration.
- compositions can also be prepared in an ointment base or as a powder for topical use.
- EXAMPLE 1 Laminated enteric coated tablet To make up a total of 100,000 enteric coated tablets of erythromycin for subsequent lamination with the sulfonamides, a homogeneous mixture of sixteen pounds, eight ounces of lactose U. S. P. and an equivalent amount of bolted starch is prepared and granulated with a sucrosestarch paste.
- the sucrose-starch paste consists of one part bolted starch; two parts fifty percent sucrose syrup, and seven parts deionized water. Each part equals one pound, six ounces and grains. These granules are dried.
- Twenty-three pounds, twelve ounces of purified crystalline base of erythromycin is granulated with a mixture consisting of three parts of a 12 /2 percent sucrosesyrup and one part of denatured ethanol. This mixture amounts to eleven pounds, five ounces, and 56 grains. One pound, one ounce, and 63 grains of white mineral oil U. S. P. viscosity is added during the wet granulating process. The granules are screened and dried.
- Both dried granulations are then screened again, mixed intimately and lubricated with eleven ounces, 188 grains of bolted starch; three pounds, nine ounces of bolted talc; and five ounces, 313 grains of a very fine powder of calcium stearate. This amount of material will then prepare 100,000 tablets by compressing on a rotary tablet machine with a three-eighth inch punch. The tablets are then assayed for potency and moisture.
- the coating on the tablet must be thick enough at this stage so that at least eleven out of twelve tablets will resist artificial gastric juice (pH 1.2) for one hour at 37 degrees centigrade, and all twelve must disintegrate in pH 6.8 buffer in less than one hour.
- Inert diluents and lubricants such as lactose, starch, or talc, can be used in a manner well known to the art to adjust the volume of the capsule fill and to facilitate handling. If soft elastic gelatin capsules are desired, the
- powders can be suspended in peanut oil. gelled with two percent aluminum monostearate before capsulating.
- EXAMPLE 4 Flavored granules for the extemporaneous preparation of a fluid
- the following dry powdered ingredients are mixed in together: 2.3 grams of erythromycin glutarate, 2.0 grams of sulfadiazine, 2.0 grams of sulfamerazine, 2.0 grams of sulfaguanidine, 370 grains of sucrose and 8 grains of sodium citrate.
- the whole is granulated with an alcoholwater solution, containing the flavors and color, and dried. These dried granules are placed in a sixty-milliliter bottle and are then ready for dissolving in an aqueous vehicle prior to use.
- a therapeutic composition comprising erythromycin and at least one sulfonamide drug.
- a therapeutic composition comprising erythromycin and at least three sulfonamide drugs.
- a therapeutic composition comprising erythromycin and sulfadiazine.
- a therapeutic composition comprising erythromycin, sulfadiazine, sulfamerazine and sulfamethazine.
- An oral therapeutic composition comprising erythromycin glutarate, sulfadiazine, sulfamerazine and sulfaguanidine.
- a therapeutic composition comprising erythromycin lactate, sulfadiazine, sulfacetamide, and sulfamerazine.
- a therapeutic composition comprising an active salt of erythromycin and at least one sulfonamide drug.
- a therapeutic composition comprising an active ester of erythromycin and at least one sulfonamide drug.
- An oral therapeutic composition comprising enteric coated erythromycin and at least one sulfonamide drug.
- An oral therapeutic composition comprising an enteric coated core containing erythromycin as the essential active ingredient and a mixture of sulfadiazine, sulfamerazine and sulfamethazine as the essential active ingredients outside the enteric coat.
- Thatcher and MacLean Synergistic Action Between Sulfonamides, Certain Dyes, and Streptomycin, J. Urology, May 1947, pp. 902-926.
- Pentresarnide penicillin plus sulfamerazine, sulfadiazine, and sulfamethazine, the three most soluble, least toxic systemic sulfonamides
- Drugs and Cos Ind., Octo ber 1950, p. 496.
Description
. other antibiotics.
2,866,735 THERAPEUTIC COMPOSHTION F MATTER Robert E. Himelick, Kalamazoo Township, Kalamazoo County, Mich., assignor to The Upjohn Company, Kalamazoo, Mich., a corporation of Michigan No Drawing. Application March 18, 1954 Serial No. 417,214
15 Claims. (Cl. 167-65) This invention relates to a combination of antibacterial substances, and more particularly relates to the combination of erythromycin and the sulfonamides. Among the greatest medical advances of the last quarter century is the development and use of antibacterial substances to combat infectious diseases. The medical art is in constant search of new and better antibacterial substances and combinations thereof. Since bacteria develop resistant strains to the commonly used antibacterial agents and since patients develop sensitivities to antibacterial agents which are used too often, the search for new agents is a continuing and ceaseless struggle for the medical art. Most combinations of antibacterial agents provide little advantage over the individual antibacterial agents used alone. Occasionally, an unusually good combination is discovered.
It is therefore an object of the present invention to States Patent ,provide novel preparations containing two different types of antibacterial agents which are admirably suited for the treatment of infectious diseases. Another object is to provide novel preparations containing erythromycin and sulfonamides which preparations possess an unusually broad antibacterial spectrum. Another object is to provide such antibacterial preparations possessing a hard hitting, reinforced antibacterial action against the organisms responsible for the majority of infections. Another object is to provide such novel preparations which are effective against strains of organisms resistant to other antibiotics. Another object is to provide such novel preparations which do not render organisms resistant to Still another object is to provide such novel preparations which may be used in patients sensitive to other antibiotics. Still another object is to provide such novel preparations which forestall the development of resistant organisms. Still another object is to provide novel antibacterial preparations which are well tolerated and have negligible allergenic properties. Still another object is to provide such preparations which contain a combination of several sulfonamides in order to minimize possibility of crystalluria renal damage and lessen the incidence of allergic reactions. Other objects will be apparent to those skilled in the art to which this invention pertains.
The foregoing and additional objects are accomplished in the present invention by providing a composition of matter containing erythromycin as one essential active ingredient and at least one of the sulfonamides as a second essential active ingredient. In its most preferred embodiment the novel composition of the present invention consists of erythromycin and three sulfonamides, the most preferred sulfonamides being snlfadiazine, sulfamerazine, and sulfamethazine. In its broadest sense the present invention consists in the unexpected properties attributable to the combination of erythromycin with the sulfonamides. The antibacterial advantages of the combination have been clearly demonstrated for erythromycin with one sulfonamide drug, e. g., sulfadiazine. However, the. sulfapyrirnidines (sulfadiazine, sulfamerazine and sulfamethazine) are still regarded as outstandingly efficient in the treatment of bacterial infection. It is therefore that particular combination of sulfonamides which is most preferred for combination with erythromycin in the composition of the present invention. A combination of sevaral sulfonamides is used for reasons other than the broad concept of the present invention. The most outstanding attributes of mixed sulfonamide therapy are the same here as that known in the art, i. e., such a mixture lessens renal complications and decreases patient sensitivity.
The term erythromycin is used herein in its generic sense and denotes erythromycin itself, which is characterized as a nitrogenous base, erythromycin B, and the acid addition salts and esters thereof. It is more fully described in U. S. Patent 2,653,899, issued on September 29, 1953 and Pettinga et al. J. A. C. S. 76: 569-571 1954).
The term sulfonamide drug includes sulfanilamide and the various sulfanilamide derivatives involving replacement of a hydrogen atom on the amino and/or amido groups by another group; for example, sulfamethazine, sulfacetamide, sulfamerazine, sulfadiazine, sulfadimetine, sulfisoxizole, sulfaguanidine, sulfapyridine, sulfathiazole, and phthalylsulfathiazole, succinylsulfathiazole, and the like.
In general the novel compositions of the present inven tion are prepared in a conventional manner, taking into account the pecularities of the components thereof. The preferred manner of administration is oral, and the preferred oral form is an enteric coated tablet. Palatable liquid diluents can be used but their use is not preferred since erythromycin is adversely etfected by gastric secretion in the stomach. Therefore, a dry preparation can be protected by enteric coatings which do not dissolve in the stomach but which will dissolve in the upper intestine where there is no such adverse effect upon erythromycin. Typical examples of such enteric coating materials inelude salol (phenyl salicylate), tolu balsam, shellac, casein, keratin, cellulose acetate phthalate, carboxyvention are not considered critical to the present invention, although the preferred amounts are illustrated in the examples given below.
In one embodiment of the present invention erythromycin and the triple sulfonamides are separated by preparation of a single enteric coated compressed tablet containing erythromycin and laminating it with the triple sulfonamides. The triple sulfonamides are rolled onto the enteric coated erythromycin tablet as in conventional pill making. Color coats and polish are applied.
More specifically, the erythromycin is granulated with suitable materials conventionally used in the art, screened and dried. The dried granules are lubricated and com pressed into tablets of the proper size and weight. The compressed tablet of erythromycin is then coated with cellulose acetate phthalate coating solution. The enteric coated tablet is then air dried overnight. At this stage the tablet must resist artificial gastric juice (pH 1.2) for at least one hour and must disintegrate in pH 6.8 buffer solution is less than one hour. The tablets are then treated with a solution of sucrose in water and the mixed triple sulfonamides are dusted on between syrup applications. After all of the sulfonamide powder has been added, the tablets are colored with syrup containing suitable dyes. The finished tablets are polished with waxes.
In the laminated tablet described above, it has been found that the laminated sulfonamides are removed after approximately five minutes in artificial gastric juice. The
enteric coated erythromycin core will resist the attack of 3 artificial gastric juice for at least two hours but will disintegrate upon transfer to an alkaline buffer solution of pH 6.8 or artificial intestinal juice (pH 6.9) within one hour. Usually the disintegration time in the. alkaline buffer solution is more in the order. of fifteen .to thirty minutes.
Another embodiment similar to the above is an enteric coated tablet containing a mixture of both erythromycin and sulfonamides. In the first embodiment the sulfonamides were laminated on the enteric coated erythromyein tablet.
Another method of preparing an oral preparation having the same characteristics as the above consists of preparing an enteric coated compressed tablet or pill containing the erythromyein, placing it into a hard gelatin capsule, and powder filling the triple sulfonamides. Thc compressed tablet used here should be relatively small as compared to the compressed tablet of erythromycin described above; e. g. a one-quarter inchpunch as compared with a three-eighth inchpunch for the laminated tablet. The cellulose acetate phthalate coating is applied as previously described and the tablets or tablet inserts, as they are often called, are dried overnight. In this preparation, the gelatin capsule dissolves in the stomach exposing the sulfonamides to the action of the stomach juices. The enteric coated erythromyein is impervious to the hydrochloric acid in the stomach and remains unchanged until it passes into the intestinal tract where the erythromyein tablet or pill readily disintegrates. This tablet insert should have the disintegration specifications previously outlined.
For most liquid oral preparations it is preferred to use relatively insoluble esters and salts of erythromycin since these have a lesser tendency to be inactivated by the acid in the stomach, and they are usually more palatable. Even the free base of erythromyein could be used in such liquid oral preparations since the acid in the stomach does not prevent the attainment of thera peutic levels, but this is not the most preferable form by this means of administration. Among the insoluble esters preferred in liquid oral preparations are the stearate, cyclopentylpropionate, laureate and the ethyl car bonate. An illustrative salt which is also so useful is the stearic acid salt. Any of the conventional liquid vehicles used in pharmaceutical practice which are not incompatible with the active ingredients .of the novel composition of the present invention can be used to prepare the liquid oral embodiment thereof.
Oil suspensions of the novel composition of the present invention can also be prepared. For these, as well as other oral embodiments, taste is an important factor. A soluble ester of erythromycin, i. e., the glutarate, has been found to be most useful in reducing the bitter taste of the free base. One example of such an oil suspension contains the following active ingredients for each five cubic centimeters of finished product:
Milligrams Erythromycin lactate 500 Sulfadiazine 167 Sulfacetamide 167 Sulfamerazine 167 The composition of the present invention can also be prepared as granules, especially for pediatric purposes. These granules can be dissolved in water or dispersed in foods immediately prior to use. These granules are generally prepared in packets containing a single dose. A typical pediatric formula contains the following amounts of active material as sugar coated granules:
The composition of the present invention can be prepared in a sterile vehicle for parenteral use, although this is not the preferred form of administration. The compositions can also be prepared in an ointment base or as a powder for topical use.
The following examples are illustrative of the compositions of the present invention but are not to be construed as limiting.
EXAMPLE 1 Laminated enteric coated tablet To make up a total of 100,000 enteric coated tablets of erythromycin for subsequent lamination with the sulfonamides, a homogeneous mixture of sixteen pounds, eight ounces of lactose U. S. P. and an equivalent amount of bolted starch is prepared and granulated with a sucrosestarch paste. The sucrose-starch paste consists of one part bolted starch; two parts fifty percent sucrose syrup, and seven parts deionized water. Each part equals one pound, six ounces and grains. These granules are dried. Twenty-three pounds, twelve ounces of purified crystalline base of erythromycin is granulated with a mixture consisting of three parts of a 12 /2 percent sucrosesyrup and one part of denatured ethanol. This mixture amounts to eleven pounds, five ounces, and 56 grains. One pound, one ounce, and 63 grains of white mineral oil U. S. P. viscosity is added during the wet granulating process. The granules are screened and dried. Both dried granulations are then screened again, mixed intimately and lubricated with eleven ounces, 188 grains of bolted starch; three pounds, nine ounces of bolted talc; and five ounces, 313 grains of a very fine powder of calcium stearate. This amount of material will then prepare 100,000 tablets by compressing on a rotary tablet machine with a three-eighth inch punch. The tablets are then assayed for potency and moisture.
After assaying, the tablets are given several coats of cellulose acetate phthalate in absolute denatured alcoholacetone solution in accordance with U. S. Patent 2,196,768. Tale is used for dusting, and the tablets are air dried overnight.
The coating on the tablet must be thick enough at this stage so that at least eleven out of twelve tablets will resist artificial gastric juice (pH 1.2) for one hour at 37 degrees centigrade, and all twelve must disintegrate in pH 6.8 buffer in less than one hour.
Each group of ten thousands of these tablets are given several applications of a gelatin syrup, dusting with a powder containing the following ingredients:
pounds ounces grains sulfadiazine, U. S. P 2 145 SulfameraZine, U. S. P. 2 145 Sulfamethazine 2 145 Lactose, U. S. I 305 Acacia powder 372 T 0 make up 1000 capsules 100 grams of erythromycin and 83.3 grams of each of sulfadiazine, sulfamerazine and sulfamethazine are mixed thoroughly as dry powders until uniform and filled into hard gelatin capsules.
Inert diluents and lubricants such as lactose, starch, or talc, can be used in a manner well known to the art to adjust the volume of the capsule fill and to facilitate handling. If soft elastic gelatin capsules are desired, the
powders can be suspended in peanut oil. gelled with two percent aluminum monostearate before capsulating.
EXAMPLE 3 Tablets tablet desired.
, EXAMPLE 4 Flavored granules for the extemporaneous preparation of a fluid The following dry powdered ingredients are mixed in together: 2.3 grams of erythromycin glutarate, 2.0 grams of sulfadiazine, 2.0 grams of sulfamerazine, 2.0 grams of sulfaguanidine, 370 grains of sucrose and 8 grains of sodium citrate. The whole is granulated with an alcoholwater solution, containing the flavors and color, and dried. These dried granules are placed in a sixty-milliliter bottle and are then ready for dissolving in an aqueous vehicle prior to use.
It is to be understood that the invention is not to be limited to the exact details of operation or compounds shown and described, as obvious modifications and equivalents will be apparent to one skilled in the art, and the invention is therefore to be limited only by the scope of the appended claims.
I claim:
1. A therapeutic composition comprising erythromycin and at least one sulfonamide drug.
2. A therapeutic composition comprising erythromycin and at least two sulfonamide drugs.
3. A therapeutic composition comprising erythromycin and at least three sulfonamide drugs.
4. A therapeutic composition comprising erythromycin and sulfadiazine.
5. A therapeutic composition comprising erythromycin, sulfadiazine and sulfamerazine.
6. A therapeutic composition comprising erythromycin, sulfadiazine, sulfamerazine and sulfamethazine.
7. An oral therapeutic composition comprising erythromycin glutarate, sulfadiazine, sulfamerazine and sulfaguanidine.
8. A therapeutic composition comprising erythromycin lactate, sulfadiazine, sulfacetamide, and sulfamerazine.
9. A therapeutic composition comprising erythromycin, sulfadiazine, sulfamerazine, sulfacetamide and sulfamethazine.
10. A therapeutic composition comprising an active salt of erythromycin and at least one sulfonamide drug.
11. A therapeutic composition comprising an active ester of erythromycin and at least one sulfonamide drug.
12. An oral therapeutic composition comprising enteric coated erythromycin and at least one sulfonamide drug.
13. An oral enteric coated composition comprising erythromycin and at least one sulfonamide drug.
14. An oral therapeutic composition comprising an enteric coated core containing erythromycin as the essential active ingredient and a mixture of sulfadiazine, sulfamerazine and sulfamethazine as the essential active ingredients outside the enteric coat.
15. An oral therapeutic composition comprising an erythromycin tablet coated with an enteric coating of cellulose acetate phthalate and the combination of sulfadiazine, sulfamerazine, and sulfamethazine laminated thereon.
References Cited in the file of this patent UNITED STATES PATENTS Zapapas July 2, 1957 OTHER REFERENCES Burger: Medicinal Chemistry, Intersci. Publ., N. Y., 1951, vol. II, pp. 718 and 719.
Powell et al.: Lab. Studies of Combinations of Several Antibiotic Agents, Antibiotics and Chemotherapy, July 1953, PP- 701-708.
Unlisted Drugs, Ilotycin-Sulfa, November 30, 1953, p. 162, col. 2 (dates back to September 28, 1953, Am. Druggist, p. 47).
Thatcher and MacLean: Synergistic Action Between Sulfonamides, Certain Dyes, and Streptomycin, J. Urology, May 1947, pp. 902-926.
Price et al.: Studies of the Combined Action of Antibiotics and Sulfonamides, Am. J. Pub. Health, March 1949, pp. 340344.
Pentresarnide (penicillin plus sulfamerazine, sulfadiazine, and sulfamethazine, the three most soluble, least toxic systemic sulfonamides), Drugs and Cos. Ind., Octo ber 1950, p. 496.
Kirby: J. A. M. A., September 16, 1950, pp. 233-236, at page 233. (Sulfonarnides are also often administered in conjunction with penicillin or other agents. Triple sulfonamide mixtures, which reduce the incidence of crystalluria have gained widespread popularity.)
Claims (1)
15. AN ORAL THERAPEUTIC COMPOSITION COMPRISING AN ERYTHROMYCIN TABLET COATED WITH AN ENTERIC COATING OF CELLULOSE ACETATE PHTHALATE AND THE COMBINATION OF SULFADIAZINE, SULFAMERAZINE, AND SULFAMETHAZINE LAMINATED THEREON.
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US417214A US2866735A (en) | 1954-03-18 | 1954-03-18 | Therapeutic composition of matter |
Applications Claiming Priority (1)
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US417214A US2866735A (en) | 1954-03-18 | 1954-03-18 | Therapeutic composition of matter |
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US2866735A true US2866735A (en) | 1958-12-30 |
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US417214A Expired - Lifetime US2866735A (en) | 1954-03-18 | 1954-03-18 | Therapeutic composition of matter |
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Cited By (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3081233A (en) * | 1960-08-08 | 1963-03-12 | Upjohn Co | Enteric-coated pilules |
US3242049A (en) * | 1963-05-20 | 1966-03-22 | Ncr Co | Process for making enterically useful complex of spiramycin and product thereof |
US3279997A (en) * | 1963-10-22 | 1966-10-18 | Herbert D Schneyer | Enteric coated calcium lactate tablets containing an antihistamine and thiamine chloride |
US4289751A (en) * | 1979-06-29 | 1981-09-15 | Merck & Co., Inc. | Effervescent enteric-coated formulation of soluble form of erythromycin and therapeutic use thereof |
US4863741A (en) * | 1985-03-25 | 1989-09-05 | Abbott Laboratories | Tablet composition for drug combinations |
US4874614A (en) * | 1985-03-25 | 1989-10-17 | Abbott Laboratories | Pharmaceutical tableting method |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2798024A (en) * | 1954-06-02 | 1957-07-02 | Lilly Co Eli | Composite enteric tablet of erythromycin and sulfonamides |
-
1954
- 1954-03-18 US US417214A patent/US2866735A/en not_active Expired - Lifetime
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2798024A (en) * | 1954-06-02 | 1957-07-02 | Lilly Co Eli | Composite enteric tablet of erythromycin and sulfonamides |
Cited By (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3081233A (en) * | 1960-08-08 | 1963-03-12 | Upjohn Co | Enteric-coated pilules |
US3242049A (en) * | 1963-05-20 | 1966-03-22 | Ncr Co | Process for making enterically useful complex of spiramycin and product thereof |
US3279997A (en) * | 1963-10-22 | 1966-10-18 | Herbert D Schneyer | Enteric coated calcium lactate tablets containing an antihistamine and thiamine chloride |
US4289751A (en) * | 1979-06-29 | 1981-09-15 | Merck & Co., Inc. | Effervescent enteric-coated formulation of soluble form of erythromycin and therapeutic use thereof |
US4863741A (en) * | 1985-03-25 | 1989-09-05 | Abbott Laboratories | Tablet composition for drug combinations |
US4874614A (en) * | 1985-03-25 | 1989-10-17 | Abbott Laboratories | Pharmaceutical tableting method |
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