US3122475A - Circulatory adjuvant shell elements for cardiac glycoside suppository cores - Google Patents
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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
- A61K9/02—Suppositories; Bougies; Bases therefor; Ovules
- A61K9/025—Suppositories; Bougies; Bases therefor; Ovules characterised by shape or structure, e.g. hollow layered, coated
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/73—Rosaceae (Rose family), e.g. strawberry, chokeberry, blackberry, pear or firethorn
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
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- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S424/00—Drug, bio-affecting and body treating compositions
- Y10S424/15—Suppositories
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- the efiect resulting from the successive administration of a circulatory adjuvant and a cardiac glycoside at timed intervals has been designated the Interval Eifect by Carrel.
- the circulatory adjuvant is given sufficient time to be absorbed into the circulatory system and the cardiac glycoside is immediately thereafter absorbed, a truly synergistic therapeutic effect results.
- Such interval eifeot is different in kind from the mere plural administration of different doses of the same therapeutic agent and depends upon the cooperative functions of the two specific medicaments resulting from sequential administration of first the circulatory adjuvant such as camphor and then at a specific time interval thereafter, the cardiac glycoside.
- a further object of the present invention is to provide for the specifically timed sequential administration of a circulatory adjuvant and a cardiac glycoside without necessitating undue use of the physicians time and without causing the patient undue pain or discomfort.
- a plural medicament containing layered suppository for the treatment of heart decompensation comprising an outer suppository shell having a melting point approximating normal body temperatures (about 3738 C.) containing a circulatory adjuvant such as camphor and an inner suppository core contained Within and surrounded by the shell, the core having a melting point a few degrees lower than normal body temperatures, preferably about 34-35 C., containing a cardiac glycoside, most preferably' strophanthin.
- the suppository of the invention possesses an outer shell including a frusto conical section and a conoidal section, the bases of which are integral with one another.
- Such configuration of a plural medicamentcontaining suppository has been disclosed in the copending application of Walther I. Bensegger and Johann H. Schaeppi, Serial No. 524,983, filed July 28, 1955, now abandoned.
- the outer suppository shell 12 comprises a circulatory adjuvant dispersed in a liquefable carrier
- the inner core 11 contains a cardiac gly'coside dispersed in a relatively more readily liquefiable carrier.
- the method of formation of the suppository of this invention is similar to that disclosed in the aforesaid copending application and comprises pouring a liquid coating mass for the suppository shell containing a circulatory adjuvant around a mold core, which core extends outwardly from a casting chamber in the form of a base section comprising a conoid adjoining and integral with a frusto conical section taper-ing toward the chamber mouth, cooling to solidify the shell, removing the mold core from the mold and then pouring and solidifying within the hardened shell a liquid coating mass for the suppository core containing a cardiac glycoside.
- the outer suppository shell containing the circulatory adjuvant Upon insertion of the suppository of this invention into body orifices, the outer suppository shell containing the circulatory adjuvant first liquefies and is absorbed into the blood stream.
- the suppository shell which melts at about body temperature (3738 C.) permits the total assimilation of the adjuvant such as camphor within ten snaaars tofifteen minutes" of administration of the suppository. Within the minute period the adjuvant acts upon the circulatory system to effect increase of the blood supply to the right atrium of the heart.
- the carrier for the cardiac glycoside in the suppository core is so compounded as'to melt at a lower temperature than the shell, at about 3435 'C., so as to achieve much more rapid liquefaction and actuation of the active glycoside in the blood stream.
- the shell carrier is a fat-like substance which serves to insulate'the core material even after liquefaction of the shelland, in order to provide rapid actuation of the glycoside, a lower melting core material is utilized. It has been found that the cardiac glycoside will achieve its positive inotropic effect Within five to ten minutes of complete liquefaction of the suppository shell, i.e., within fifteen to twenty-five minutes of administration of the suppository of this invention.
- the suppository core contains a cardiac glycoside dispersed in a suitable carrier, which carrier can be any of those well known in the art, such. as cocoa-butter (oil of theobroma), solidified glycerin, lard or a paraffinic wax.
- a suitable carrier can be any of those well known in the art, such. as cocoa-butter (oil of theobroma), solidified glycerin, lard or a paraffinic wax.
- the composition of the core is so controlled that the melting point of the core is between about 34 and 35 C.
- An emulsifying 'agent is included in the core composition to insure the homogeneous dispersion of the cardiac glycoside upon liquefaction of the fat-like carrier materials.
- Emulsifying agents of the non-ionic type such as derivatives of sorbitol, polyglycol ethers and the like, may be employed as the emulsifying agents in question.
- cardiac glycosides such as strophanthin, digitalis, digitoxiin, scilloren A, krataegus, bufalin, or the like
- glycoside derivatives such as the active aglycones (e.g. strophanthidin and periplogenin)
- experimental tests indicate that by far the most effective glycoside for the practice of this invent-ion is strophanthin.
- the strophanthin is contained within the suppository core in arnounts of from 0.03% to 0.15% by weight, based on the weight of the core medicament carrier.
- the core will represent from about onefifth to one-third of the total weight of the suppository, the shell the remaining four-fifths to two-thirds.
- the suppository shell contains a circulatory adjuvant dispersed in a medicament carrier, which latter may be cocoa-butter, solidified glycerin, lard or a parafiinic wax.
- a medicament carrier which latter may be cocoa-butter, solidified glycerin, lard or a parafiinic wax.
- the amounts of the carrier and adjuvant are adjusted so that the shell melts at about body temperature, VtiZ. 37- 38" C. in this fashion absorption of the adjuvant, such as camphor, takes places in ten to fifteen minutes after rectal administration.
- the adjuvant such as camphor
- Camphor is the preferred adjuvant since it is absorbed into the blood stream relatively rapidly 'by rectal suppository administration and produces the least blood pressure increase while simultaneously promoting the motivity of the diagram.
- the circulatory adjuvant such as camphor
- the circulatory adjuvant is employed in the suppository shell in amounts ranging from about 9% to 15% by weight, based on the weight of the shell medicament carrier.
- the adjuvant may be employed at the lower percentage for amounts of the cardiac glycoside up to about 0.075% of the weight of the carrier for the glycoside, but as the amount of the glycoside is increased above that value, it is preferred to increase the amount of the adjuvant to a maximum of about 15% by weight of its carrier.
- Example A suppository composition of the present invention was prepared according to the method and with the apwas added and, after agitation, the mixture was poured.
- the liquid melt strophanthin was added and, after agitation, the mixture was poured within the solidified suppository shell and allowed to harden to form the suppository core.
- the emulsifying agent employed was Absorbticnshasis 90, a product of Th. Muhlethaler S.A.,
- emulsifier comprises a mixture. of saturated high fatty alcohols and non-ionic surface active agents, derived from S'orbitol; the emulsifying agent had a melting point of 34 C., a pH of 7 and absorbed nine times its volume of water.
- the finished suppository was found to Weigh 2.7 grams, of which 2 grams comprised the outer shell.
- the suppository shell which melted at 3738 C., contained the.
- the core of the suppository which melted at 34-35" C., contained by weight percentages, the following:
- the outer suppository shell Upon rectal administration, the outer suppository shell was found to completely liquefy in fifteen minutes and the suppository core, which melted at a lower tempera-' ture, was totally liquefied within five minutes thereafter.
- a novel suppository prepared according to the present invention for achieving the synergistic therapeutic effect resulting from the successive administration at timed intervals of a circulatory adjuvant and a cardiac glycoside.
- a plural medicament-containing layered suppositoryfor the treatment of heart decompensation comprising,
- an outer shell having. a melting point of 37-38 C. and containing, a circulatory adjuvant, and'an; inner core contained within and surrounded bysaid shell having a melting point of 34-35 C. and containingv a cardiac glycoside.
- said glycoside included in an amount of from 0.103% to.
- a plural medicament-containing layered suppository for the treatment of heart decompensation comprising, in combination, an outer shell having a melting point of 37-38 C. and containing a circulatory adjuvant, said shell including a frusto conical section and a conoidal section, the bases of said sections being integral with one another, and an inner core enclosed within said shell having a melting point of 3435 C., said core containing a cardiac glycoside.
- a suppository as defined in claim 5 wherein said shell contains camphor as said adjuvant, said camphor being assimilable within the circulatory system of the patient within about 10 to 15 minutes of the administration of said suppository, and said core contains strophanthin as said glycoside, said strophanthin being absorbed by said circulatory system subsequent to the absorption of said camphor and within 15 to 25 minutes of the administration of said suppository.
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Description
Feb. 25, 1964 J. H. SCHAEPPI 3,122,475
CIRCULATORY ADJUVANT SHELL ELEMENTS FOR CARDIAC GLYCOSIDE SUPPOSITORY CORES Filed Feb. 25
l2 SHE A Cl JNVENTOR. J'O/MMV flaw/6H SCH/45PM BY M M W ATTOIQ/VEYS United States Patent 3,122,475 CIRCULATORY ADJUVANT SIELL ELEMENTS FOR CARDEAC GLYCDSWE SUPPGSITGRY CGRES Johann Heinrich Sehaeppi, Mitlodi, Switzerland, assignor to Dr. Schaeppi Alrtiengeseilschaft, Mitiodi, Switzerland, a corporation of Switzerland Filed Feb. 25, 1960, Ser. No. 10,996 8 Claims. (Cl. 167-64) This invention relates to a suppository effective in the treatment of heart disease, and more particularly to a multiple lay'er suppository containing sequentially acting medicaments effective in treating heart decompensation.
The various cardiac glycosides have in recent years found increased utility in therapeutic treatments designed to improve heart muscle actiw'ty and tone. However, it has been noted that While such medicaments possess beneficial positive inotropic effects, nevertheless they do not simultaneously supply the heart with sufficient amounts of blood. The effects of such deficiency are manifest; on one hand, the cardiac glycosides fail to fulfill their function of assisting the heart muscles to maintain adequate circulation, while, on the other hand, use of these medicaments, particularly in cases involving elevated therapeutic dosages, may presage systaltic heart failure. In the latter situation the blood supply may actually so lag behind the increased activity of the heart muscles, induced by the heart glycoside, that the physiological residual blood may be pumped out of the heart and idle beating of the chambers will result.
Clinical tests have indicated that the effect of the cardiac glycosides may be significantly improved after a preliminary administration of a circulatory adjuvant, such as camphor. In fact, it has been shown that the danger of systaltic heart stoppages, after administration of strophanthin and other cardiac glycosides, is greatly diminished by such a preliminary treatment (Brodhage and Carrel, Arzneimittelforchung, 1957, No. 7). Such effect is believed to result from the adjuvants action effecting increased flow of blood to the right atrium, thereby increasing the heart discharge capacity. Thus, the cardiac glycoside, which is thereafter administered, functions to improve circulation without danger of systaltic failure.
Pharmacologically, the efiect resulting from the successive administration of a circulatory adjuvant and a cardiac glycoside at timed intervals has been designated the Interval Eifect by Carrel. When the circulatory adjuvant is given sufficient time to be absorbed into the circulatory system and the cardiac glycoside is immediately thereafter absorbed, a truly synergistic therapeutic effect results. Such interval eifeot is different in kind from the mere plural administration of different doses of the same therapeutic agent and depends upon the cooperative functions of the two specific medicaments resulting from sequential administration of first the circulatory adjuvant such as camphor and then at a specific time interval thereafter, the cardiac glycoside.
Unfortunately, circulatory adjuvants such as camphor cannot be administered intravenously but have rather heretofore been administered by intramuscular injection. When camphor dosages are given in such fashion, it has been found that between one and two hours are required for absorption into the circulatory system. In order therefore to achieve the beneficial results accruing from the Interval Effect, the physician must wait for one hour or more before administering the cardiac glycoside. Such delay has proven quite a burden upon both the practicing physician and the patient, particularly in view ice of the fact that in many' cases daily injections of the therapeutic agents are necessary.
It is accordingly an object of the present invention to provide means for administering a circulatory adjuvant and a cardiac glycoside at desired intervals to effectuate treatment of heart decompensation.
A further object of the present invention is to provide for the specifically timed sequential administration of a circulatory adjuvant and a cardiac glycoside without necessitating undue use of the physicians time and without causing the patient undue pain or discomfort.
Other objects and advantages of the present invention will become apparent from the following detailed description of the invention and the appended claims defining the scope thereof.
In accordance with my invention, a plural medicament containing layered suppository for the treatment of heart decompensation is provided, comprising an outer suppository shell having a melting point approximating normal body temperatures (about 3738 C.) containing a circulatory adjuvant such as camphor and an inner suppository core contained Within and surrounded by the shell, the core having a melting point a few degrees lower than normal body temperatures, preferably about 34-35 C., containing a cardiac glycoside, most preferably' strophanthin. I have surprisingly found that absorption of circulatory adjuvants such as camphor in the rectum is much more rapid than through muscular tissue, and that such a plural medicament-containing suppository having the indicated melting points can be compounded so as to successively liquefy the circulatory adjuvant and cardiac glycoside at those shorter intervals (of the order of a quarter hour) necessary for the production of the Interval Effect; While plural medicament suppositories have previously been described in the literature, I have for the first time unexpectedly discovered that combination of ingredients which successfully produce a plural medicament suppository capable of sequential actuation of the various medicaments at specifically timed intervals.
Preferably, the suppository of the invention possesses an outer shell including a frusto conical section and a conoidal section, the bases of which are integral with one another. Such configuration of a plural medicamentcontaining suppository has been disclosed in the copending application of Walther I. Bensegger and Johann H. Schaeppi, Serial No. 524,983, filed July 28, 1955, now abandoned.
One embodiment of the suppository of this invention is shown in the attached drawing wherein the outer suppository shell 12 comprises a circulatory adjuvant dispersed in a liquefable carrier, and the inner core 11 contains a cardiac gly'coside dispersed in a relatively more readily liquefiable carrier.
7 The method of formation of the suppository of this invention is similar to that disclosed in the aforesaid copending application and comprises pouring a liquid coating mass for the suppository shell containing a circulatory adjuvant around a mold core, which core extends outwardly from a casting chamber in the form of a base section comprising a conoid adjoining and integral with a frusto conical section taper-ing toward the chamber mouth, cooling to solidify the shell, removing the mold core from the mold and then pouring and solidifying within the hardened shell a liquid coating mass for the suppository core containing a cardiac glycoside.
Upon insertion of the suppository of this invention into body orifices, the outer suppository shell containing the circulatory adjuvant first liquefies and is absorbed into the blood stream. The suppository shell, which melts at about body temperature (3738 C.) permits the total assimilation of the adjuvant such as camphor within ten snaaars tofifteen minutes" of administration of the suppository. Within the minute period the adjuvant acts upon the circulatory system to effect increase of the blood supply to the right atrium of the heart. The carrier for the cardiac glycoside in the suppository core, on the other hand, is so compounded as'to melt at a lower temperature than the shell, at about 3435 'C., so as to achieve much more rapid liquefaction and actuation of the active glycoside in the blood stream. The shell carrier is a fat-like substance which serves to insulate'the core material even after liquefaction of the shelland, in order to provide rapid actuation of the glycoside, a lower melting core material is utilized. It has been found that the cardiac glycoside will achieve its positive inotropic effect Within five to ten minutes of complete liquefaction of the suppository shell, i.e., within fifteen to twenty-five minutes of administration of the suppository of this invention.
The suppository core contains a cardiac glycoside dispersed in a suitable carrier, which carrier can be any of those well known in the art, such. as cocoa-butter (oil of theobroma), solidified glycerin, lard or a paraffinic wax. The composition of the core is so controlled that the melting point of the core is between about 34 and 35 C. An emulsifying 'agent is included in the core composition to insure the homogeneous dispersion of the cardiac glycoside upon liquefaction of the fat-like carrier materials. Emulsifying agents of the non-ionic type, such as derivatives of sorbitol, polyglycol ethers and the like, may be employed as the emulsifying agents in question.
While any of the cardiac glycosides, such as strophanthin, digitalis, digitoxiin, scilloren A, krataegus, bufalin, or the like, may be employed in the suppository composition, as may glycoside derivatives such as the active aglycones (e.g. strophanthidin and periplogenin), experimental tests indicate that by far the most effective glycoside for the practice of this invent-ion is strophanthin.
The strophanthin is contained within the suppository core in arnounts of from 0.03% to 0.15% by weight, based on the weight of the core medicament carrier.
In general, the core will represent from about onefifth to one-third of the total weight of the suppository, the shell the remaining four-fifths to two-thirds. By the use of these weight ratios along with the choice of carrier needed, the desired Interval Efiect is achieved.
The suppository shell contains a circulatory adjuvant dispersed in a medicament carrier, which latter may be cocoa-butter, solidified glycerin, lard or a parafiinic wax. The amounts of the carrier and adjuvant are adjusted so that the shell melts at about body temperature, VtiZ. 37- 38" C. in this fashion absorption of the adjuvant, such as camphor, takes places in ten to fifteen minutes after rectal administration. Camphor is the preferred adjuvant since it is absorbed into the blood stream relatively rapidly 'by rectal suppository administration and produces the least blood pressure increase while simultaneously promoting the motivity of the diagram. However, other adjuvants such as hydroxy camphor, trans-r-oxocamphor, 1-(3-hydroxyph'enyl) 1 hydroxy-Z-ethylaminethanol, 8- nicotinic acid diethylarnide, or other sympathomimetics or circulatory analeptics can less preferably be used.
The circulatory adjuvant such as camphor, is employed in the suppository shell in amounts ranging from about 9% to 15% by weight, based on the weight of the shell medicament carrier. The adjuvant may be employed at the lower percentage for amounts of the cardiac glycoside up to about 0.075% of the weight of the carrier for the glycoside, but as the amount of the glycoside is increased above that value, it is preferred to increase the amount of the adjuvant to a maximum of about 15% by weight of its carrier.
Example A suppository composition of the present invention was prepared according to the method and with the apwas added and, after agitation, the mixture was poured.
into a casting chamber as described in the above mentioned application. After cooling and solidification thereof, the mold core was removed from the casting chamber leaving the hardened suppository shell therein.
After formation of the suppository shell, a mixture of Estarinum B, with paraffin wax (melting point 50-52? C.)
and an emulsifying agent was heated and liquefied. To-
the liquid melt strophanthin was added and, after agitation, the mixture was poured within the solidified suppository shell and allowed to harden to form the suppository core. The emulsifying agent employed was Absorbticnshasis 90, a product of Th. Muhlethaler S.A.,
Nyon, Switzerland, which emulsifier comprises a mixture. of saturated high fatty alcohols and non-ionic surface active agents, derived from S'orbitol; the emulsifying agent had a melting point of 34 C., a pH of 7 and absorbed nine times its volume of water.
The finished suppository was found to Weigh 2.7 grams, of which 2 grams comprised the outer shell. The suppository shell, which melted at 3738 C., contained the.
following weight percentages of constituents:
Percent:
Estarinum l3 77" Paraflin wax 13'.5' Camphor 9.5
The core of the suppository, which melted at 34-35" C., contained by weight percentages, the following:
Percentv Estarinum B (carrier) 88.964 Paraffin wax 5.5 Absorbtionsbasis (emulsifying agent) 5.5 Strophanthin 0.036.
Upon rectal administration, the outer suppository shell was found to completely liquefy in fifteen minutes and the suppository core, which melted at a lower tempera-' ture, was totally liquefied within five minutes thereafter.
The above example is intended to be illustrative, and
not limiting, of a novel suppository prepared according to the present invention for achieving the synergistic therapeutic effect resulting from the successive administration at timed intervals of a circulatory adjuvant and a cardiac glycoside.
Since difierent embodiments of the invention may be.
made without departing from the scope thereof, it is intended that all matter contained in the above description shall be interpreted as illustrative and not in a limiting sense.
What is claimed is:
1. A plural medicament-containing layered suppositoryfor the treatment of heart decompensation comprising,
in combination, an outer shell having. a melting point of 37-38 C. and containing, a circulatory adjuvant, and'an; inner core contained within and surrounded bysaid shell having a melting point of 34-35 C. and containingv a cardiac glycoside.
2. A suppository as defined in claim 1 whereinsaidshell contains a medicament carrierand a circulatory adjuvant, saidadjuvant included in an amount of from about 9% to 15% by weight of said carrier, and said core contains a medicament carrier and acardiac glycoside,.
said glycoside included in an amount of from 0.103% to.
0.15% by weight of said last mentioned carrier.
3. A suppository as defined in claim 2 wherein said circulatory adjuvant comprises camphor and. said cardiac glycoside comprises strophanthin.
4. A suppository as defined in claim 1 wherein said shell contains camphor as said adjuvant, said camphor being assimilable within the circulatory system of the patient Within about to minutes of the administration of said suppository, and said core contains strophanthin as said glycoside, said strophanthin being absorbed by said circulatory system subsequent to the absorption of said camphor and within 15 to minutes of the administration of said suppository.
5. A plural medicament-containing layered suppository for the treatment of heart decompensation comprising, in combination, an outer shell having a melting point of 37-38 C. and containing a circulatory adjuvant, said shell including a frusto conical section and a conoidal section, the bases of said sections being integral with one another, and an inner core enclosed within said shell having a melting point of 3435 C., said core containing a cardiac glycoside.
6. A suppository as defined in claim 5 wherein said shell contains a medicament carrier and a circulatory adjuvant, said adjuvant included in an amount of from about 9% to 15% by Weight of said carrier, and said core contains a medicament carrier and a cardiac glycoside, said glycoside included in an amount of from 0.3% to 0.15% by Weight of said last mentioned carrier.
7. A suppository as defined in claim 6 wherein said circulatory adjuvant comprises camphor and said cardiac glycoside comprises strophanthin.
8. A suppository as defined in claim 5 wherein said shell contains camphor as said adjuvant, said camphor being assimilable within the circulatory system of the patient within about 10 to 15 minutes of the administration of said suppository, and said core contains strophanthin as said glycoside, said strophanthin being absorbed by said circulatory system subsequent to the absorption of said camphor and within 15 to 25 minutes of the administration of said suppository.
References Cited in the file of this patent UNITED STATES PATENTS OTHER REFERENCES Brodhage et al.: Arzneimittel-forchung, vol. 7, (1957), pp. 387-388.
Lendle et al.: Arch. fiir Experimentalle Pathologie und Pharmakolocie, vol. 138, (1938), pp. 317-327.
U.S. Dispensatory, 25th ed., Lippincott Co., Philadelphia, Pa., (1955), p. 232-4.
Sollman: Manual of Pharmacology, 8th ed., Saunders Co., Philadelphia, Pa. (1957), pp. 249-251.
Ser. No. 143,736, Hatfner (A.P.C.), published May 11, 1943.
Claims (1)
1. A PLURAL MEDICAMENT-CONTAINING LAYERED SUPPOSITORY FOR THE TREATMENT OF HEART DECOMPENSATION COMPRISING, IN COMBINATION, AN OUTER SHELL HAVING A MELTING POINT OF 37-38* C. AND CONTAINING A CIRCULATORY ADJUVANT, AND AN INNER CORE CONTAINED WITHIN AND SURROUNED BY SAID SHELL HAVING A MELTING POINT OF 34-35*C. AND CONTAINING A CARDIAC GLYCOSIDE.
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Cited By (15)
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JPS50157518A (en) * | 1974-06-11 | 1975-12-19 | ||
USB524121I5 (en) * | 1974-11-15 | 1976-02-03 | ||
US3948263A (en) * | 1974-08-14 | 1976-04-06 | Minnesota Mining And Manufacturing Company | Ballistic animal implant |
JPS54157820A (en) * | 1978-05-30 | 1979-12-13 | Res Inst For Prod Dev | Preparation of multi-layered suppository base |
US4685911A (en) * | 1984-02-21 | 1987-08-11 | Yamanouchi Pharmaceutical Co., Ltd. | Patch |
US4879119A (en) * | 1984-02-21 | 1989-11-07 | Yamanouchi Pharmaceutical Co., Ltd. | Patch |
US4892890A (en) * | 1984-11-01 | 1990-01-09 | G. D. Searle And Company | External analgesic compositions |
US5151271A (en) * | 1981-08-27 | 1992-09-29 | Nitti Electric Industrial Co., Ltd. | Pressure-sensitively adhering composite medicinal preparation |
US5672359A (en) * | 1993-07-21 | 1997-09-30 | The University Of Kentucky Research Foundation | Multicompartment hard capsule with control release properties |
EP1993672A2 (en) * | 2006-01-31 | 2008-11-26 | The University Of Toledo | Na/k-atpase ligand |
US8691947B2 (en) | 2010-01-13 | 2014-04-08 | The University Of Toledo | Materials related to sodium/potassium adenosine triphosphatase and Src |
US8981051B2 (en) | 2006-10-31 | 2015-03-17 | The University Of Toledo | Na+/K+-ATPase-specific peptide inhibitors/activators of Src and Src family kinases |
US9114126B2 (en) | 2009-09-16 | 2015-08-25 | The University Of Toledo | Na/K-ATPase ligands, ouabain antagonists, assays and uses thereof |
USD801518S1 (en) * | 2012-11-21 | 2017-10-31 | Therapeuticsmd, Inc. | Pharmaceutical capsule |
US20220287963A1 (en) * | 2015-03-12 | 2022-09-15 | Cristcot Llc | Hydrocortisone Acetate Suppository Formulation For Treatment Of Disease |
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US669716A (en) * | 1899-08-29 | 1901-03-12 | Charles B Tippett | Topical remedy. |
US1525285A (en) * | 1922-04-24 | 1925-02-03 | Gabbola Raffaele | Composition for use as a salve or ointment |
US2055083A (en) * | 1932-07-13 | 1936-09-22 | Winthrop Chem Co Inc | Pharmaceutical preparation |
US2054989A (en) * | 1933-12-30 | 1936-09-22 | Us Ind Alcohol Co | Compositions for application to the human skin |
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Cited By (22)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS50157518A (en) * | 1974-06-11 | 1975-12-19 | ||
US3948263A (en) * | 1974-08-14 | 1976-04-06 | Minnesota Mining And Manufacturing Company | Ballistic animal implant |
USB524121I5 (en) * | 1974-11-15 | 1976-02-03 | ||
US3982536A (en) * | 1974-11-15 | 1976-09-28 | Minnesota Mining And Manufacturing Company | Ballistic inoculation of animals and projectile therefor |
JPS54157820A (en) * | 1978-05-30 | 1979-12-13 | Res Inst For Prod Dev | Preparation of multi-layered suppository base |
JPS5632289B2 (en) * | 1978-05-30 | 1981-07-27 | ||
US5151271A (en) * | 1981-08-27 | 1992-09-29 | Nitti Electric Industrial Co., Ltd. | Pressure-sensitively adhering composite medicinal preparation |
US4685911A (en) * | 1984-02-21 | 1987-08-11 | Yamanouchi Pharmaceutical Co., Ltd. | Patch |
US4879119A (en) * | 1984-02-21 | 1989-11-07 | Yamanouchi Pharmaceutical Co., Ltd. | Patch |
US4892890A (en) * | 1984-11-01 | 1990-01-09 | G. D. Searle And Company | External analgesic compositions |
US5672359A (en) * | 1993-07-21 | 1997-09-30 | The University Of Kentucky Research Foundation | Multicompartment hard capsule with control release properties |
EP1993672A2 (en) * | 2006-01-31 | 2008-11-26 | The University Of Toledo | Na/k-atpase ligand |
US20090226513A1 (en) * | 2006-01-31 | 2009-09-10 | Zijian Xie | Na/K-ATpase Ligand |
EP1993672A4 (en) * | 2006-01-31 | 2009-09-16 | Univ Toledo | Na/k-atpase ligand |
US8906891B2 (en) | 2006-01-31 | 2014-12-09 | The University Of Toledo | Na/K-ATPase ligand |
US8981051B2 (en) | 2006-10-31 | 2015-03-17 | The University Of Toledo | Na+/K+-ATPase-specific peptide inhibitors/activators of Src and Src family kinases |
US9663561B2 (en) | 2006-10-31 | 2017-05-30 | The University Of Toledo | Methods of treatment of cancer using SRC-modulating peptides |
US9114126B2 (en) | 2009-09-16 | 2015-08-25 | The University Of Toledo | Na/K-ATPase ligands, ouabain antagonists, assays and uses thereof |
US8691947B2 (en) | 2010-01-13 | 2014-04-08 | The University Of Toledo | Materials related to sodium/potassium adenosine triphosphatase and Src |
US8835171B2 (en) | 2010-01-13 | 2014-09-16 | The University Of Toledo | Materials and methods related to sodium/potassium adenosine triphosphase and cholesterol |
USD801518S1 (en) * | 2012-11-21 | 2017-10-31 | Therapeuticsmd, Inc. | Pharmaceutical capsule |
US20220287963A1 (en) * | 2015-03-12 | 2022-09-15 | Cristcot Llc | Hydrocortisone Acetate Suppository Formulation For Treatment Of Disease |
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