US3004894A - Therapeutic composition comprising tetracycline and a dioxolane - Google Patents
Therapeutic composition comprising tetracycline and a dioxolane Download PDFInfo
- Publication number
- US3004894A US3004894A US804577A US80457759A US3004894A US 3004894 A US3004894 A US 3004894A US 804577 A US804577 A US 804577A US 80457759 A US80457759 A US 80457759A US 3004894 A US3004894 A US 3004894A
- Authority
- US
- United States
- Prior art keywords
- tetracycline
- dioxolane
- methanol
- dimethyl
- vial
- 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
Classifications
-
- 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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- 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
- A61K31/65—Tetracyclines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/22—Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
Definitions
- the tetracycline compositions for parenteral administration have utilized water as the vehicle.
- the administration of such aqueous preparations have had the disadvantages of slow absorption and slow systemic distribution from the site of injection and trauma and pain at the site of injection.
- a surfactant as an aid to preparing the composition, a surfactant.
- compositions of the present invention are useful for the administration of tetracycline and are superior to aqueous tetracycline compositions from the therapeutic standpoint in that they produce higher blood levels of tetracycline and are less painful to the patient.
- R is a hydrogen, methyl or ethyl; R is a hydrogen, methyl, or ethyl; and R is a hydrogen, methyl, carbinol, or ethylol.
- the preferred compound is 2,2-dimethyl-l,3-dioxolane- 4-methanol, wherein R and R are methyl and R is carbinol.
- the other dioxolane compounds of this group suitable as a vehicle for tetracycline, are 1,3-dioxolane, 4- methyl-l,3-dioxolane, 1,3-dioxolane-4-methanol, 1,3-dioxolane-4-ethanol, 2,2-dimethyl-l,3-dioxolane, 2,2,4-t1'imethyl-1,3-dioxolane, 2,2-dimethyl-l,3-dioxolane-4-ethanol, 2,2-diethyl-l,3-dioxolane, 2,2-diethyl-4-methyl-l,3- dioxolane, 2,2-diethyl-1,3-dioxolane-4-methanol, 2,2-diethyl-1,3-dioXolane-4-
- tetracycline as used in the specification and claims herein shall be taken to include the pharmaceutically and physiologically acceptable free base, organic and inorganic salts, as well as chelates, esters, complexes, and
- the solubility of the free base in 2-,2-dimethyl-l,3-dioxolanel-methanol is greater than 250 mg./cc. and the inorganic acid salts such as the hydrochloride or phosphate are more slowly soluble and in concentrations of more than about 50 mg./cc. form suspensions. Whether the composition forms a solution or suspension in the dioxolane, however, the composition is therapeutically superior to the equivalent aqueous composition.
- This invention enables a higher concentration of tetracycline up to 250 mg/cc. and more.
- a concentration greater than 250 mg./ cc. of an insol luble tetracycline increases the viscosity of the compositions and although compositions having this increased viscosity are suitable for veterinary purposes Where use of a large needle is permissible, it is preferred that compositions for human use have a concentration of 250 mg./cc. or less. Of course, a lesser concentration can be used tothe m'nimum for therapeutic eflicacy.
- compositions can be prepared having a tetracycline concentration from 1 mg. or less/cc. to about 500 mg./cc., it is preferred to prepare compositions having a concentration which is relevant to the usual dosage requirements.
- the compositions are preferably supplied in unit dosage form, i.e., in single dose amounts of 1 or 2 cc. having 250 mg. of tetracycline or multiple dose amounts of 10 cc. having 2.5 g. of tetracycline.
- another antibiotic can be included in the compositions.
- the additional antibiotic can serve to either broaden the antibacterial speotrum of the composition or exert a synergistic eiiect with the tetracycline against particular bacteria.
- Novobiocin can be added to the compositions of the present invention to followthe preference of current medical practice for the concurrent administration of tetracycline and novobiocin.
- Pencillin V can also be included with tetracycline in the compositions and the two antibiotics can be present either as separate ingredients or in the form of the tetracycline salt of penicillin V.
- a water soluble and parenterally acceptable acid is advantageously included in the compositions of the present invention wherein the tetracycline is present as the acid addition salt.
- the addition of an acid to the composition increases further the rapid absorption and systemic distribution of the antibiotic.
- Citric acid is the preferred acid. A concentration of about 10% w./v. citric acid is preferred for those compositions having a tetracycline concentration of about 125 mg./cc. Ascorbic acid can also be used as well as other parenterally acceptable acids such as gluconic acid, lactic acid and glycine hydrochloride.
- a local anesthetic'agent is advantageously incorporated into the compositions of the present invention as a further aid in the reduction of pain'of the injection.
- the anesthetic eflFect will begin several minutes after injection and lasts for several hours, onset and duration of action ranging with the particular agent used.
- a concentration of about 0.5 to 2% w./v. is used depending upon the particular local anesthetic agent.
- local anesthetics such as butethamine, dibucaine, procaine, tetracaine, and lidocaine, as Well as others are suitable.
- the hydrochloride salts are usually used for those compositions having an acid present.
- Pain can be further reduced by the inclusion of a compound capable of providing a magnesium ion, such as magnesium chloride and magnesium gluconate.
- a compound capable of providing a magnesium ion such as magnesium chloride and magnesium gluconate.
- Magnesium chloride is used in a preferred concentration of about 2 moles or more to 1 mole of tetracycline,
- a surfactant in a concentration of about 0.5% is ada 3 vantageously present as an adjuvant to the preparation and administration of those compositions forming suspensions. This agent aids in the suspending of the insoluble particles in the dioxolane, insuring accurate dosage when aliquots of the composition are administered.
- the surfactant also prevents freezing of the syringe and clogging of the lumen of the hypodermic needle. Polyoxyethylene sorbitan monolaurate is preferred.
- compositions of the present invention are best prepared in final form at the time of administration by simply adding the dioxolane from one container to the dry powder tetracycline mixture in the other container and shaking until dispersed.
- the final composition is to be a suspension and a surfactant is employed, the latter is deposited over the surface of the tetracycline particles.
- the surfactant is fluid, itcan be sprayed 'over the powder; however, better distribution is obtained if the surfactant is dissolved in a volatile fluid (which is not a solvent for the tetracycline) and the solution sprayed onto the tetracycline.
- a slurry can be made of the tetracycline and the surfactant-solvent solution, and the solvent allowed to evaporate.
- the coated teracycline particles are then blended with the remaining ingredients until uniformly with the tetracycline powder blend.
- Two cubic centimeter glass ampoules are aseptically filled with sterile 2,2-dimethyl-1,3-dioxolane-4-methanol and sealed.
- the 2,2-dimethyl-1,3- dioxolane-4-methanol is added to the vial containing the antibiotic in an amount sufiicient to make 2 cc. of solution.
- the vial is shaken until the powders are dissolved and the solution withdrawn in a syringe and administered, preferably intramuscularly;
- the prepara: tion gives less pain and higher tetracycline blood levels than an equivalent composition utilizing an aqueous vehicle.
- the powders are bolted through No. 9 bolting cloth and thoroughly blended.
- the blended powder mixture is filled into vials, each vial containing 615 mg. of powder mixture.
- the vials are sterilized by exposure to ethylene oxide vapors and capped.
- the 2,2-dimethyl-1,3-dioxolane-4-methanol is added to the vial containing the antibiotic in an amount sufficient to make 2 cc. of solution.
- the vial is shaken until the powders are dissolved and the solution withdrawn in a syringe and administered, preferably intramuscularly.
- the preparation gives less pain and higher tetracycline blood levels than an equivalent composition utilizing an aqueous vehicle.
- Example 3 G Tetracycline base, milled 287.5 Calcium acid novobiocin, micronized 143.7 a-DiethyIaminO-Z,6-aceto-xylidide 40
- the powders are bolted through No. 9 bolting cloth and thoroughly blended.
- the blended powder mixture is filled into vials, each vial containing 471.2 mg. of powder mixture.
- the vials are sterilized by exposure to ethylene oxide vapors and capped.
- the 2,2-dimethyl-1,3- dioxolane-4-methanol is added to the vial containing the antibiotics in an amount s-ufiicient to make 2 Co.
- the vial is shaken to uniformly distribute the antibiotics and the final compositions withdrawn in a syringe and administered, preferably intramuscularly.
- the preparation gives less pain and higher tetracycline blood levels than an equivalent composition utilizing an aqueous vehicle.
- Example 4 Tetracycline phosphate, micronized, 1%. lecithin coated 287.5 Citric acid anhydrous, micronized 222 a-Diethylamino 2,6-aceto-xylidide hydrochloride,
- micronized 44 The dry powders are mixed together until uniformly dispersed. 553.5 mg. of the mixture are filled into a vial, sterilized with ethylene oxide and capped.
- dioxolane-4-methanol is added to the vial containing the antibiotic in an amount suflicient to make 2 cc. of suspension,
- the vial. is shaken to suspend the antibiotic and the suspension withdrawn in a syringe and administered, preferably intramuscularly.
- the preparation gives less pain and higher tetracycline blood levels than, an equivalent composition utilizing an aqueous vehicle. 4
- the 2,2-dimethyl-l,3- dioxolane-4-methanol is added to the vial containing the antibiotic in an amount suflicient to make 2 cc. of suspension.
- the vial is shaken to suspend the antibiotic and the suspension withdrawn in a syringe and administered, preferably intramuscularly.
- the preparation gives less pain and higher tetracycline blood levels than an equivalent composition utilizing an aqueous vehicle.
- Example 6 G Tetracycline phosphate, micronized 287.5 Citric acid, anhydrous, micronized 220 Tetracaine hydrochloride, micronized 44 Polyoxyethylene sorbitan monolaurate 10
- the polyoxyethylene sorbitan is dissolved in about 250 cc. of chloroform and the solution mixed with the tetracycline until the tetracycline particles are uniformly wetted.
- the chloroform is allowed to evaporate and the cake dried at 40 C. for 2 hours.
- the tetracycline cake is comminuted and the powder blended with the remaining ingredients. 561.5 mg. of the mixture is filled into a vial, sterilized with ethylene oxide and capped.
- the 2,2-dimethyl-1,3- dioxolane-tmethanol is added to the vial containing the antibiotic in an amount sufficient to make 2 cc. of suspension.
- Ihe vial is shaken to suspend the antibiotic and the suspension withdrawn in a syringe and administered, preferably intramuscularly.
- the preparation gives less pain and higher tetracycline blood levels than an equivalent composition utilizing an aqueous vehicle.
- the polyoxyethylene sorbitan is dissolved in about 250 cc. of chloroform and the solution mixed with the tetracycline until the tetracycline particles are uniformly wetted.
- the chloroform is allowed to evaporate and the cake dried at 40 C. for 2 hours.
- the tetracycline cake is comminuted and the powder blended with the remaining ingredients. 561.5 mg. of the mixture is filled into a vial, sterilized with ethylene oxide and capped.
- the 2,2-dimethy1-1,3- dioxolane-4-methanol is added to the vial containing the antibiotic in an amount suflicient to make 2 cc. of suspension.
- the vial is shaken to suspend the antibiotic and the suspension withdrawn in a syringe and administered, preferably intramuscularly.
- the preparation gives less pain and higher tetracycline blood levels than an equivalent composition utilizing an aqueous vehicle.
- the polyoxyethylene sorbitan is dissolved in about 500 cc. of chloroform and the solution mixed with the tetracycline until the tetracycline particles are uniformly wetted.
- the chloroform is allowed to evaporate and the cake dried at 40 C. for 2 hours.
- the tetracycline cake is comminuted and the powder blended with the remaining ingredients. 774 mg. of the mixture is filled into a vial, sterilized with ethylene oxide and capped.
- the 2,2-dimethyl-1,3- dioxolane-4-methanol is added to the vial containing the antibiotic in an amount sufficient to make 2 cc. of suspension.
- the vial is shaken to suspend the antibiotic and the suspension withdrawn in a syringe and administered, preferably intramuscularly.
- the preparation gives less pain and higher tetracycline blood levels than an equivalent composition utilizing an aqueous vehicle.
- Example 9 G Tetracycline phosphate, micronized 575 Polyoxyethylene sorbitan monolaurate 10
- the polyoxyethylene sorbitan monolaurate is dissolved in about 500 cc. of chloroform and the solution mixed with the tetracycline until the tetracycline particles are uniformly wetted.
- the chloroform is allowed to evaporate and the cake dried at 40 C. for 2 hours.
- the tetracycline cake is comminuted. 5 mg. of the powder is filled into a vial, sterilized with ethylene oxide and capped.
- the 2,2-dimethyl-l,3- dioxolane-tmethanol is added to the vial containing the antibiotic in an amount sufficient to make 2 cc. of suspension.
- the vial is shaken to suspend the antibiotic and the suspension withdrawn in a syringe and administered, preferably intramuscularly.
- the preparation gives less pain and higher tetracycline blood levels than an equivalent composition utilizing an aqueous vehicle.
- Example 10 G 6-demethyl tetracycline, milled 287.5 u-Diethylamino-2,6-aceto-xylidide 40
- the powders are bolted through No. 9 bolting cloth and thoroughly blended.
- the blended powder mixture is filled into vials, each via'l containing 325.5 mg. of powder mixture.
- the vials are sterilized by exposure to ethylene oxide vapors and capped.
- the 2,2-dimethyl-l,3- dioxolane-4-methanol is added to the vial containing the antibiotic in an amount suflicient to make 2 cc.
- the vial is shaken to disperse the antibiotic and the composition withdrawn in a syringe and administered, preferably in tramuscularly.
- the preparation gives less pain and higher tetracycline blood levels than an equivalent composition utilizing an aqueous vehicle.
- composition of claim 1 wherein the tetracycline is the tetracycline free base.
- composition of claim 1 wherein the tetracycline is a acid addition salt of tetracycline free base.
- composition of claim 1 wherein the tetracycline is the penicillin V salt of tetracycline free base.
- composition of claim 1 whereinthetetracycline is G-demethyl tetracycline.
- composition of claim 1 wherein the tetracycline is pyrrolidino-methyl-tetracycline.
- a therapeutic composition for parenteral administration comprising a pharmacologically acceptable acid addition salt of tetracycline free base as an essential active ingredient, a non-toxic, parcnterally acceptable, Water soluble acid/and, as a vehicle therefor, 2,2-dimethyll ,3 -dioxolane-4-methanel.
- a therapeutic composition for parenteral administration comprising from' about 5 mg./cc. to about 5.00 nag/cc. of tetracycline as an essential active ingredient, and, as a vehicle therefor, 2,2-dimethyl-1,3-dioxolane-4- methanol. 7.
- a therapeutic composition for parenteral administration comprising about 12.5% tetracyclinephosphate, about 10% citric acid, about 2.0% a-diethylamino-2,6- aceto-Xylidide hydrochloride, about 0.5% polyoxyethylene sorbitan monolaurate and 2,2-dimethyl-1,3-dioxolane- 4-rnethanol.
- a therapeutic composition for parenteral administration comprising about,12,5% tetracycline phosphate,-
- citric. acid about 2. 0%' tetracaine hydrochloride, about 0.5 polyoxyethylene sorbitan monolaurate and 2,2-dimethyh1,3-diox0lane-4-methanol.
Description
United States Patent 3,004,894 THERAPEUTIC COMPOSITION COMPRISING TETRACYCLINE AND A DIOXOLANE Richard H. Johnson, Kalamazoo, and Donald P. Wallach, Richland, Mich., assignors to The Upjohn Company, Kalamazoo, Mich., a corporation of Delaware No Drawing. Filed Apr. 7, 1959, Ser. No. 804,577 Claims. (Cl. 167-82) This invention relates to a therapeutic composition of tetracycline and more particularly to a parenterally acceptable dosage form of tetracycline with a dioxolane vehicle.
Prior to the present invention the tetracycline compositions for parenteral administration have utilized water as the vehicle. However, the administration of such aqueous preparations have had the disadvantages of slow absorption and slow systemic distribution from the site of injection and trauma and pain at the site of injection.
The therapeutic compositions of the present invention comprise tetracycline and a dioxolane. The compositions can be either solutions or suspensions depending upon the particular form of tetracycline used, the concentration of the particular tetracycline and the presence of solubilizers. Advantageously the compositions can include a parenterally acceptable acid, a local anesthetic, a compound capable of providing a magnesium ion, and,
as an aid to preparing the composition, a surfactant.
Other antibiotics can be included in the compositions, especially novobiocin for its synergistic efiect with tetracycline.
The compositions of the present invention are useful for the administration of tetracycline and are superior to aqueous tetracycline compositions from the therapeutic standpoint in that they produce higher blood levels of tetracycline and are less painful to the patient.
The dioxolane compounds suitable for the compositions of the present invention can be represented by the following graphic formula:
R is a hydrogen, methyl or ethyl; R is a hydrogen, methyl, or ethyl; and R is a hydrogen, methyl, carbinol, or ethylol.
The preferred compound is 2,2-dimethyl-l,3-dioxolane- 4-methanol, wherein R and R are methyl and R is carbinol. The other dioxolane compounds of this group, suitable as a vehicle for tetracycline, are 1,3-dioxolane, 4- methyl-l,3-dioxolane, 1,3-dioxolane-4-methanol, 1,3-dioxolane-4-ethanol, 2,2-dimethyl-l,3-dioxolane, 2,2,4-t1'imethyl-1,3-dioxolane, 2,2-dimethyl-l,3-dioxolane-4-ethanol, 2,2-diethyl-l,3-dioxolane, 2,2-diethyl-4-methyl-l,3- dioxolane, 2,2-diethyl-1,3-dioxolane-4-methanol, 2,2-diethyl-1,3-dioXolane-4-ethanol, 2-methyl-1,3-dioxolane, 2, 4-dimethyl-L3-dioxolane, Z-methyl-l,3-dioxolane-4-methanol, 2-methyl-l,3-dioxolane-4-ethanol, 2-ethyl-l,3-dioxolane, 2-ethyl-4-methyl-1,3-dioxolane, 2-ethyl-l,3-dioxolane-4-methanol, 2-ethyl-1,3-dioxolane-4-ethanol, Z-ethyl- 2-methyl-l,3-dioxolane, 2,4-dimethyl2-ethy1-1,3-dioxolane, 2-ethyl-2-methyl-1,3-dioxolane-4-methanol, 2-ethyl- 2-methyl-1,3-dioxolane-4-ethanol.
The term tetracycline as used in the specification and claims herein shall be taken to include the pharmaceutically and physiologically acceptable free base, organic and inorganic salts, as well as chelates, esters, complexes, and
2 6-demethy1 tetracycline and pyrrolidino-methyl-tetracycline.
The solubility of the free base in 2-,2-dimethyl-l,3-dioxolanel-methanol is greater than 250 mg./cc. and the inorganic acid salts such as the hydrochloride or phosphate are more slowly soluble and in concentrations of more than about 50 mg./cc. form suspensions. Whether the composition forms a solution or suspension in the dioxolane, however, the composition is therapeutically superior to the equivalent aqueous composition.
Current medical practice utilizes aqueous compositions having a tetracycline concentration of about 50 mg./ cc. and mg./ cc. This invention enables a higher concentration of tetracycline up to 250 mg/cc. and more. A concentration greater than 250 mg./ cc. of an insol luble tetracycline increases the viscosity of the compositions and although compositions having this increased viscosity are suitable for veterinary purposes Where use of a large needle is permissible, it is preferred that compositions for human use have a concentration of 250 mg./cc. or less. Of course, a lesser concentration can be used tothe m'nimum for therapeutic eflicacy.
Although compositions can be prepared having a tetracycline concentration from 1 mg. or less/cc. to about 500 mg./cc., it is preferred to prepare compositions having a concentration which is relevant to the usual dosage requirements. To this end the compositions are preferably supplied in unit dosage form, i.e., in single dose amounts of 1 or 2 cc. having 250 mg. of tetracycline or multiple dose amounts of 10 cc. having 2.5 g. of tetracycline.
In addition to the tetracycline, another antibiotic can be included in the compositions. Advantageously the additional antibiotic can serve to either broaden the antibacterial speotrum of the composition or exert a synergistic eiiect with the tetracycline against particular bacteria. Novobiocin can be added to the compositions of the present invention to followthe preference of current medical practice for the concurrent administration of tetracycline and novobiocin. Pencillin V can also be included with tetracycline in the compositions and the two antibiotics can be present either as separate ingredients or in the form of the tetracycline salt of penicillin V.
A water soluble and parenterally acceptable acid is advantageously included in the compositions of the present invention wherein the tetracycline is present as the acid addition salt. The addition of an acid to the composition increases further the rapid absorption and systemic distribution of the antibiotic.
Citric acid is the preferred acid. A concentration of about 10% w./v. citric acid is preferred for those compositions having a tetracycline concentration of about 125 mg./cc. Ascorbic acid can also be used as well as other parenterally acceptable acids such as gluconic acid, lactic acid and glycine hydrochloride.
A local anesthetic'agent is advantageously incorporated into the compositions of the present invention as a further aid in the reduction of pain'of the injection. The anesthetic eflFect will begin several minutes after injection and lasts for several hours, onset and duration of action ranging with the particular agent used. A concentration of about 0.5 to 2% w./v. is used depending upon the particular local anesthetic agent. local anesthetics such as butethamine, dibucaine, procaine, tetracaine, and lidocaine, as Well as others are suitable. The hydrochloride salts are usually used for those compositions having an acid present.
Pain can be further reduced by the inclusion of a compound capable of providing a magnesium ion, such as magnesium chloride and magnesium gluconate. Magnesium chloride is used in a preferred concentration of about 2 moles or more to 1 mole of tetracycline,
A surfactant in a concentration of about 0.5% is ada 3 vantageously present as an adjuvant to the preparation and administration of those compositions forming suspensions. This agent aids in the suspending of the insoluble particles in the dioxolane, insuring accurate dosage when aliquots of the composition are administered. The surfactant also prevents freezing of the syringe and clogging of the lumen of the hypodermic needle. Polyoxyethylene sorbitan monolaurate is preferred.
The compositions of the present invention are best prepared in final form at the time of administration by simply adding the dioxolane from one container to the dry powder tetracycline mixture in the other container and shaking until dispersed.
In preparing the dry powder mixture the various dry ingredients are first reduced to a finely divided state. Examples of the many ways in which comminution can be carried out can be found in chapter 11 of Remingtons Practice of Pharmacy, 11th edition, Mack Publishing Company, Easton, Pennsylvania, U.S.A., 1956. The preferred method of reducing the particle size of the various ingredients is by use of an air micronizer; particles so reduced by this method will hereinafter be described as micronized. i
When the final composition is to be a suspension and a surfactant is employed, the latter is deposited over the surface of the tetracycline particles. If the surfactant is fluid, itcan be sprayed 'over the powder; however, better distribution is obtained if the surfactant is dissolved in a volatile fluid (which is not a solvent for the tetracycline) and the solution sprayed onto the tetracycline. Alternatively, a slurry can be made of the tetracycline and the surfactant-solvent solution, and the solvent allowed to evaporate. The coated teracycline particles are then blended with the remaining ingredients until uniformly with the tetracycline powder blend.
. The following examples are illustrative of the process and products of the present invention, but are not to be construed as limiting.
' Example 1 I a G, Tetracycline base, milled 287.5 a-Diethylamino-2,fi-aceto-xylidide 40 The powders are bolted through No. 9 bolting cloth and thoroughly blended. The blended powder mixture is, filled into vials, each vial containing 327,5 mg. of powder mixture. The vials are sterilized by exposure to ethylene oxide vapors and capped.
Two cubic centimeter glass ampoules are aseptically filled with sterile 2,2-dimethyl-1,3-dioxolane-4-methanol and sealed.
At the time for administration the 2,2-dimethyl-1,3- dioxolane-4-methanol is added to the vial containing the antibiotic in an amount sufiicient to make 2 cc. of solution. The vial is shaken until the powders are dissolved and the solution withdrawn in a syringe and administered, preferably intramuscularly; When so used, the prepara: tion gives less pain and higher tetracycline blood levels than an equivalent composition utilizing an aqueous vehicle.
a-Diethylamino-2,6-aceto-xylidide The powders are bolted through No. 9 bolting cloth and thoroughly blended. The blended powder mixture is filled into vials, each vial containing 615 mg. of powder mixture. The vials are sterilized by exposure to ethylene oxide vapors and capped.
Two cubic centimeterlglass ar'npoules are aseptically filled with V sterile 2;,2-dimethyl-1,3-dioxolane-4-methanol and sealed. 7 7
At the time for administration the 2,2-dimethyl-1,3-dioxolane-4-methanol is added to the vial containing the antibiotic in an amount sufficient to make 2 cc. of solution. The vial is shaken until the powders are dissolved and the solution withdrawn in a syringe and administered, preferably intramuscularly. Whenso used, the preparation gives less pain and higher tetracycline blood levels than an equivalent composition utilizing an aqueous vehicle.
Example 3 G. Tetracycline base, milled 287.5 Calcium acid novobiocin, micronized 143.7 a-DiethyIaminO-Z,6-aceto-xylidide 40 The powders are bolted through No. 9 bolting cloth and thoroughly blended. The blended powder mixture is filled into vials, each vial containing 471.2 mg. of powder mixture. The vials are sterilized by exposure to ethylene oxide vapors and capped.
Two cubic centimeter glass ampoules are aseptically filled with sterile 2,2-dimethyl-1,3-dioxolane-4-methanol and sealed.
' At the time for administration the 2,2-dimethyl-1,3- dioxolane-4-methanol is added to the vial containing the antibiotics in an amount s-ufiicient to make 2 Co. The vial is shaken to uniformly distribute the antibiotics and the final compositions withdrawn in a syringe and administered, preferably intramuscularly. When so used, the preparation gives less pain and higher tetracycline blood levels than an equivalent composition utilizing an aqueous vehicle.
Example 4 Tetracycline phosphate, micronized, 1%. lecithin coated 287.5 Citric acid anhydrous, micronized 222 a-Diethylamino 2,6-aceto-xylidide hydrochloride,
micronized 44 The dry powders are mixed together until uniformly dispersed. 553.5 mg. of the mixture are filled into a vial, sterilized with ethylene oxide and capped.
1.9 cc. of sterilized 2,2-dimethyl-1,3-dioxo1ane-4-methanol is aseptically filled into a glass vial and sealed.
At the time for administration the 2,2-dimethyl-l,3-
. dioxolane-4-methanol is added to the vial containing the antibiotic in an amount suflicient to make 2 cc. of suspension, The vial. is shaken to suspend the antibiotic and the suspension withdrawn in a syringe and administered, preferably intramuscularly. When so used, the preparation gives less pain and higher tetracycline blood levels than, an equivalent composition utilizing an aqueous vehicle. 4
The polyoxyethylene sorbitan is dissolved in about 250 cc. of chloroform and the solution mixed with the tetracycline until the tetracycline particles are uniformly wetted. The chloroform is allowed to evaporate and the cake dried at 40 C. for 2 hours. The tetracycline cake is comminuted and the powder blended With the remaining ingredients. 561.5 mg. of the mixture is filled into a vial, sterilized with ethylene oxide, and capped.
1.9 cc. of 2,2-dimethyl-1,3-dioxolane-4-methanol is aseptically filled into a glass vial and sealed.
At the time for administration the 2,2-dimethyl-l,3- dioxolane-4-methanol is added to the vial containing the antibiotic in an amount suflicient to make 2 cc. of suspension. The vial is shaken to suspend the antibiotic and the suspension withdrawn in a syringe and administered, preferably intramuscularly. When so used, the preparation gives less pain and higher tetracycline blood levels than an equivalent composition utilizing an aqueous vehicle.
Example 6 G. Tetracycline phosphate, micronized 287.5 Citric acid, anhydrous, micronized 220 Tetracaine hydrochloride, micronized 44 Polyoxyethylene sorbitan monolaurate 10 The polyoxyethylene sorbitan is dissolved in about 250 cc. of chloroform and the solution mixed with the tetracycline until the tetracycline particles are uniformly wetted. The chloroform is allowed to evaporate and the cake dried at 40 C. for 2 hours. The tetracycline cake is comminuted and the powder blended with the remaining ingredients. 561.5 mg. of the mixture is filled into a vial, sterilized with ethylene oxide and capped.
1.9 cc. of sterilized 2,2-dimethyl-1,3-dioxolane-4-methanol is aseptically filled into a glass vial and sealed.
At the time for administration the 2,2-dimethyl-1,3- dioxolane-tmethanol is added to the vial containing the antibiotic in an amount sufficient to make 2 cc. of suspension. Ihe vial is shaken to suspend the antibiotic and the suspension withdrawn in a syringe and administered, preferably intramuscularly. When so used, the preparation gives less pain and higher tetracycline blood levels than an equivalent composition utilizing an aqueous vehicle.
The polyoxyethylene sorbitan is dissolved in about 250 cc. of chloroform and the solution mixed with the tetracycline until the tetracycline particles are uniformly wetted. The chloroform is allowed to evaporate and the cake dried at 40 C. for 2 hours. The tetracycline cake is comminuted and the powder blended with the remaining ingredients. 561.5 mg. of the mixture is filled into a vial, sterilized with ethylene oxide and capped.
1.9 cc. of sterilized 2,2-dimethyl-1,3-dioxolane-4-rncthanol is aseptically filled into a glass vial and sealed.
At the time for administration the 2,2-dimethy1-1,3- dioxolane-4-methanol is added to the vial containing the antibiotic in an amount suflicient to make 2 cc. of suspension. The vial is shaken to suspend the antibiotic and the suspension withdrawn in a syringe and administered, preferably intramuscularly. When so used, the preparation gives less pain and higher tetracycline blood levels than an equivalent composition utilizing an aqueous vehicle.
The polyoxyethylene sorbitan is dissolved in about 500 cc. of chloroform and the solution mixed with the tetracycline until the tetracycline particles are uniformly wetted. The chloroform is allowed to evaporate and the cake dried at 40 C. for 2 hours. The tetracycline cake is comminuted and the powder blended with the remaining ingredients. 774 mg. of the mixture is filled into a vial, sterilized with ethylene oxide and capped.
p 1.9 cc. of 2,2-dimethyl-1,3-dioxolane-4-methanol is aseptically filled into a glass vial and sealed.
At the time for administration the 2,2-dimethyl-1,3- dioxolane-4-methanol is added to the vial containing the antibiotic in an amount sufficient to make 2 cc. of suspension. The vial is shaken to suspend the antibiotic and the suspension withdrawn in a syringe and administered, preferably intramuscularly. When so used, the preparation gives less pain and higher tetracycline blood levels than an equivalent composition utilizing an aqueous vehicle.
Example 9 G. Tetracycline phosphate, micronized 575 Polyoxyethylene sorbitan monolaurate 10 The polyoxyethylene sorbitan monolaurate is dissolved in about 500 cc. of chloroform and the solution mixed with the tetracycline until the tetracycline particles are uniformly wetted. The chloroform is allowed to evaporate and the cake dried at 40 C. for 2 hours. The tetracycline cake is comminuted. 5 mg. of the powder is filled into a vial, sterilized with ethylene oxide and capped.
1.9 cc. of 2,2-dimethyl-1,3-dioxolane-4-methanol is aseptically filled into a glass vial and sealed.
At the time for administration the 2,2-dimethyl-l,3- dioxolane-tmethanol is added to the vial containing the antibiotic in an amount sufficient to make 2 cc. of suspension. The vial is shaken to suspend the antibiotic and the suspension withdrawn in a syringe and administered, preferably intramuscularly. When so used, the preparation gives less pain and higher tetracycline blood levels than an equivalent composition utilizing an aqueous vehicle.
Example 10 G 6-demethyl tetracycline, milled 287.5 u-Diethylamino-2,6-aceto-xylidide 40 The powders are bolted through No. 9 bolting cloth and thoroughly blended. The blended powder mixture is filled into vials, each via'l containing 325.5 mg. of powder mixture. The vials are sterilized by exposure to ethylene oxide vapors and capped.
1.9 cc. of sterilized 2,2-climethyl-l,3-dioxolane-4-methano] is aseptically filled into a glass vial and sealed.
At the time for administration the 2,2-dimethyl-l,3- dioxolane-4-methanol is added to the vial containing the antibiotic in an amount suflicient to make 2 cc. The vial is shaken to disperse the antibiotic and the composition withdrawn in a syringe and administered, preferably in tramuscularly. When so used, the preparation gives less pain and higher tetracycline blood levels than an equivalent composition utilizing an aqueous vehicle.
It is to be understood that the invention is not to be limited to the exact details of operation or exact 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.
We claim:
1. A therapeutic composition for parenteral administration comprising tetracycline as an essential active ingredient and, as a vehicle therefor, 2,2-dimethyl-l,3-diox- =olane-4-methanol.
2. The composition of claim 1 wherein the tetracycline is the tetracycline free base.
3. The composition of claim 1 wherein the tetracycline is a acid addition salt of tetracycline free base.
4. The composition of claim 1 wherein the tetracycline is the penicillin V salt of tetracycline free base.
5. The composition of claim 1 whereinthetetracycline is G-demethyl tetracycline. t
6. The composition of claim 1 wherein the tetracycline is pyrrolidino-methyl-tetracycline.
7. A therapeutic composition for parenteral administration comprising a pharmacologically acceptable acid addition salt of tetracycline free base as an essential active ingredient, a non-toxic, parcnterally acceptable, Water soluble acid/and, as a vehicle therefor, 2,2-dimethyll ,3 -dioxolane-4-methanel.
8. A therapeutic composition for parenteral administration comprising from' about 5 mg./cc. to about 5.00 nag/cc. of tetracycline as an essential active ingredient, and, as a vehicle therefor, 2,2-dimethyl-1,3-dioxolane-4- methanol. 7.
9. A therapeutic composition for parenteral administration comprising about 12.5% tetracyclinephosphate, about 10% citric acid, about 2.0% a-diethylamino-2,6- aceto-Xylidide hydrochloride, about 0.5% polyoxyethylene sorbitan monolaurate and 2,2-dimethyl-1,3-dioxolane- 4-rnethanol.
10. A therapeutic composition for parenteral administration comprising about,12,5% tetracycline phosphate,-
about 10% citric. acid, about 2. 0%' tetracaine hydrochloride, about 0.5 polyoxyethylene sorbitan monolaurate and 2,2-dimethyh1,3-diox0lane-4-methanol.
ReferencesCited in the fileof this patent UNITED STATES PATENTS 2,428,805 Kharasch Oct. 14, 1947 FOREIGN PATENTS 279,099 Switzerland Mar. 1, 1952 535,471 Canada Jan. 8, 1957 793,558 Great Britain Apr. 16, 1958 OTHER REFERENCES UNITED STATES PATENT OFFICE M CERTIFICATE OF CORRECTION Patent N0. 3,004,894 October 17, 1961 Richard H. Johnson et alo It is hereby certified that error appears in the above numbered patent requiring correction and that the said Letters Patent should read as corrected below.
Column 3, line 33 for "teracycline" read tetracycline line 56, for "327, 5 mg.
read 327.5 mg column 5 l ne 68 for "200" read 220 column 6 line 73 after "is a" lnsert pharmacologically acceptable Signed and sealed this 10th day of April 1962.
(SEAL) Attest:
ERNEST W. SWIDER DAVID L. LADD Commissioner of Patents Attesting Officer
Claims (1)
1. A THERAPEUTIC COMPOSITION FOR PARENTERAL ADMINISTRATION COMPRISING TETRACYCLINE AS AN ESSENTIAL ACTIVE INGREDIENT AND, AS A VEHICLE THEREFOR, 2,2-DIMETHYL-1,3-DIOXOLANE-4-METHANOL.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US804577A US3004894A (en) | 1959-04-07 | 1959-04-07 | Therapeutic composition comprising tetracycline and a dioxolane |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US804577A US3004894A (en) | 1959-04-07 | 1959-04-07 | Therapeutic composition comprising tetracycline and a dioxolane |
Publications (1)
Publication Number | Publication Date |
---|---|
US3004894A true US3004894A (en) | 1961-10-17 |
Family
ID=25189320
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US804577A Expired - Lifetime US3004894A (en) | 1959-04-07 | 1959-04-07 | Therapeutic composition comprising tetracycline and a dioxolane |
Country Status (1)
Country | Link |
---|---|
US (1) | US3004894A (en) |
Cited By (38)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3137627A (en) * | 1962-03-12 | 1964-06-16 | Bristol Myers Co | Nu-(1-pyrrolidinomethyl) tetracycline and acid compositions for aqueous acidified injections having a ph of not more than about 4 |
FR2034890A1 (en) * | 1969-03-13 | 1970-12-18 | Diamond Shamrock Corp | |
EP0038013A2 (en) * | 1980-04-10 | 1981-10-21 | Sds Biotech Corporation | Injectable oxytetracycline compositions |
US5391785A (en) * | 1990-01-16 | 1995-02-21 | La Jolla Pharmaceutial Company | Intermediates for providing functional groups on the 5' end of oligonucleotides |
WO2004087117A2 (en) * | 2003-04-02 | 2004-10-14 | Bayer Healthcare Ag | Use of cyclic acetals/ketals for improved penetration of active substances into cells and organs |
WO2009143175A2 (en) * | 2008-05-19 | 2009-11-26 | Children's Medical Center Corporation | Sensory-specific local anesthesia and prolonged duration local anesthesia |
US20110178162A1 (en) * | 2005-10-14 | 2011-07-21 | Medical University Of South Carolina | Targeting pax2 for the induction of defb1-mediated tumor immunity and cancer therapy |
US8343945B2 (en) | 2007-12-07 | 2013-01-01 | Foamix Ltd. | Carriers, formulations, methods for formulating unstable active agents for external application and uses thereof |
US8362091B2 (en) | 2003-08-04 | 2013-01-29 | Foamix Ltd. | Foamable vehicle and pharmaceutical compositions thereof |
US8435498B2 (en) | 2002-10-25 | 2013-05-07 | Foamix Ltd. | Penetrating pharmaceutical foam |
US8486375B2 (en) | 2003-04-28 | 2013-07-16 | Foamix Ltd. | Foamable compositions |
US8486376B2 (en) | 2002-10-25 | 2013-07-16 | Foamix Ltd. | Moisturizing foam containing lanolin |
US8486374B2 (en) | 2003-08-04 | 2013-07-16 | Foamix Ltd. | Hydrophilic, non-aqueous pharmaceutical carriers and compositions and uses |
US8512718B2 (en) | 2000-07-03 | 2013-08-20 | Foamix Ltd. | Pharmaceutical composition for topical application |
US8518376B2 (en) | 2007-12-07 | 2013-08-27 | Foamix Ltd. | Oil-based foamable carriers and formulations |
US8518378B2 (en) | 2003-08-04 | 2013-08-27 | Foamix Ltd. | Oleaginous pharmaceutical and cosmetic foam |
US8618081B2 (en) | 2009-10-02 | 2013-12-31 | Foamix Ltd. | Compositions, gels and foams with rheology modulators and uses thereof |
US8636982B2 (en) | 2007-08-07 | 2014-01-28 | Foamix Ltd. | Wax foamable vehicle and pharmaceutical compositions thereof |
US8709385B2 (en) | 2008-01-14 | 2014-04-29 | Foamix Ltd. | Poloxamer foamable pharmaceutical compositions with active agents and/or therapeutic cells and uses |
US8722021B2 (en) | 2002-10-25 | 2014-05-13 | Foamix Ltd. | Foamable carriers |
US8795693B2 (en) | 2003-08-04 | 2014-08-05 | Foamix Ltd. | Compositions with modulating agents |
US8795635B2 (en) | 2006-11-14 | 2014-08-05 | Foamix Ltd. | Substantially non-aqueous foamable petrolatum based pharmaceutical and cosmetic compositions and their uses |
US8900554B2 (en) | 2002-10-25 | 2014-12-02 | Foamix Pharmaceuticals Ltd. | Foamable composition and uses thereof |
US8952152B2 (en) | 2009-03-24 | 2015-02-10 | Proteus S.A. | Methods for purifying phycotoxins, pharmaceutical compositions containing purified phycotoxins, and methods of use thereof |
US8975268B2 (en) | 2013-03-15 | 2015-03-10 | The Children's Medical Center Corporation | Neosaxitoxin combination formulations for prolonged local anesthesia |
US9072667B2 (en) | 2009-07-29 | 2015-07-07 | Foamix Pharmaceuticals Ltd. | Non surface active agent non polymeric agent hydro-alcoholic foamable compositions, breakable foams and their uses |
US9167813B2 (en) | 2009-07-29 | 2015-10-27 | Foamix Pharmaceuticals Ltd. | Non surfactant hydro-alcoholic foamable compositions, breakable foams and their uses |
US9211259B2 (en) | 2002-11-29 | 2015-12-15 | Foamix Pharmaceuticals Ltd. | Antibiotic kit and composition and uses thereof |
US9265725B2 (en) | 2002-10-25 | 2016-02-23 | Foamix Pharmaceuticals Ltd. | Dicarboxylic acid foamable vehicle and pharmaceutical compositions thereof |
US9320705B2 (en) | 2002-10-25 | 2016-04-26 | Foamix Pharmaceuticals Ltd. | Sensation modifying topical composition foam |
WO2011138678A3 (en) * | 2010-05-04 | 2016-05-26 | Foamix Ltd. | Compositions, gels and foams with rheology modulators and uses thereof |
US9439857B2 (en) | 2007-11-30 | 2016-09-13 | Foamix Pharmaceuticals Ltd. | Foam containing benzoyl peroxide |
US9539208B2 (en) | 2002-10-25 | 2017-01-10 | Foamix Pharmaceuticals Ltd. | Foam prepared from nanoemulsions and uses |
US9622947B2 (en) | 2002-10-25 | 2017-04-18 | Foamix Pharmaceuticals Ltd. | Foamable composition combining a polar solvent and a hydrophobic carrier |
US9668972B2 (en) | 2002-10-25 | 2017-06-06 | Foamix Pharmaceuticals Ltd. | Nonsteroidal immunomodulating kit and composition and uses thereof |
US9849142B2 (en) | 2009-10-02 | 2017-12-26 | Foamix Pharmaceuticals Ltd. | Methods for accelerated return of skin integrity and for the treatment of impetigo |
US9884017B2 (en) | 2009-04-28 | 2018-02-06 | Foamix Pharmaceuticals Ltd. | Foamable vehicles and pharmaceutical compositions comprising aprotic polar solvents and uses thereof |
US10398641B2 (en) | 2016-09-08 | 2019-09-03 | Foamix Pharmaceuticals Ltd. | Compositions and methods for treating rosacea and acne |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2428805A (en) * | 1947-10-14 | Dioxolanes and methods of | ||
CH279099A (en) * | 1948-01-13 | 1951-11-15 | Sharp & Dohme Inc | Process for the production of a bacteriostatic preparation. |
CA535471A (en) * | 1957-01-08 | Heinemann Bernard | Therapeutically useful tetracycline complex | |
GB793558A (en) * | 1954-07-07 | 1958-04-16 | Pfizer | Improvements in or relating to tetracycline preparations |
-
1959
- 1959-04-07 US US804577A patent/US3004894A/en not_active Expired - Lifetime
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2428805A (en) * | 1947-10-14 | Dioxolanes and methods of | ||
CA535471A (en) * | 1957-01-08 | Heinemann Bernard | Therapeutically useful tetracycline complex | |
CH279099A (en) * | 1948-01-13 | 1951-11-15 | Sharp & Dohme Inc | Process for the production of a bacteriostatic preparation. |
GB793558A (en) * | 1954-07-07 | 1958-04-16 | Pfizer | Improvements in or relating to tetracycline preparations |
Cited By (102)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3137627A (en) * | 1962-03-12 | 1964-06-16 | Bristol Myers Co | Nu-(1-pyrrolidinomethyl) tetracycline and acid compositions for aqueous acidified injections having a ph of not more than about 4 |
FR2034890A1 (en) * | 1969-03-13 | 1970-12-18 | Diamond Shamrock Corp | |
EP0038013A2 (en) * | 1980-04-10 | 1981-10-21 | Sds Biotech Corporation | Injectable oxytetracycline compositions |
EP0038013A3 (en) * | 1980-04-10 | 1982-09-22 | Sds Biotech Corporation | Injectable oxytetracycline compositions |
US5391785A (en) * | 1990-01-16 | 1995-02-21 | La Jolla Pharmaceutial Company | Intermediates for providing functional groups on the 5' end of oligonucleotides |
US5726329A (en) * | 1990-01-16 | 1998-03-10 | La Jolla Pharmaceutical Company | Modified phosphorous intermediates for providing functional groups on the 5' end of oligonucleotides |
US5786512A (en) * | 1990-01-16 | 1998-07-28 | Lajolla Pharmaceutical Company | Modified phosphorous intermediates for providing functional groups on the 5' end of oligonucleotides |
US5874552A (en) * | 1990-01-16 | 1999-02-23 | La Jolla Pharmaceutical Company | Modified phosphorous intermediates for providing functional groups on the 5' end of oligonucleotides |
US8512718B2 (en) | 2000-07-03 | 2013-08-20 | Foamix Ltd. | Pharmaceutical composition for topical application |
US9713643B2 (en) | 2002-10-25 | 2017-07-25 | Foamix Pharmaceuticals Ltd. | Foamable carriers |
US8486376B2 (en) | 2002-10-25 | 2013-07-16 | Foamix Ltd. | Moisturizing foam containing lanolin |
US9539208B2 (en) | 2002-10-25 | 2017-01-10 | Foamix Pharmaceuticals Ltd. | Foam prepared from nanoemulsions and uses |
US8741265B2 (en) | 2002-10-25 | 2014-06-03 | Foamix Ltd. | Penetrating pharmaceutical foam |
US9492412B2 (en) | 2002-10-25 | 2016-11-15 | Foamix Pharmaceuticals Ltd. | Penetrating pharmaceutical foam |
US9320705B2 (en) | 2002-10-25 | 2016-04-26 | Foamix Pharmaceuticals Ltd. | Sensation modifying topical composition foam |
US9265725B2 (en) | 2002-10-25 | 2016-02-23 | Foamix Pharmaceuticals Ltd. | Dicarboxylic acid foamable vehicle and pharmaceutical compositions thereof |
US8722021B2 (en) | 2002-10-25 | 2014-05-13 | Foamix Ltd. | Foamable carriers |
US11033491B2 (en) | 2002-10-25 | 2021-06-15 | Vyne Therapeutics Inc. | Dicarboxylic acid foamable vehicle and pharmaceutical compositions thereof |
US8435498B2 (en) | 2002-10-25 | 2013-05-07 | Foamix Ltd. | Penetrating pharmaceutical foam |
US8900554B2 (en) | 2002-10-25 | 2014-12-02 | Foamix Pharmaceuticals Ltd. | Foamable composition and uses thereof |
US10821077B2 (en) | 2002-10-25 | 2020-11-03 | Foamix Pharmaceuticals Ltd. | Dicarboxylic acid foamable vehicle and pharmaceutical compositions thereof |
US9668972B2 (en) | 2002-10-25 | 2017-06-06 | Foamix Pharmaceuticals Ltd. | Nonsteroidal immunomodulating kit and composition and uses thereof |
US10322085B2 (en) | 2002-10-25 | 2019-06-18 | Foamix Pharmaceuticals Ltd. | Dicarboxylic acid foamable vehicle and pharmaceutical compositions thereof |
US9622947B2 (en) | 2002-10-25 | 2017-04-18 | Foamix Pharmaceuticals Ltd. | Foamable composition combining a polar solvent and a hydrophobic carrier |
US8840869B2 (en) | 2002-10-25 | 2014-09-23 | Foamix Ltd. | Body cavity foams |
US10117812B2 (en) | 2002-10-25 | 2018-11-06 | Foamix Pharmaceuticals Ltd. | Foamable composition combining a polar solvent and a hydrophobic carrier |
US9211259B2 (en) | 2002-11-29 | 2015-12-15 | Foamix Pharmaceuticals Ltd. | Antibiotic kit and composition and uses thereof |
WO2004087117A2 (en) * | 2003-04-02 | 2004-10-14 | Bayer Healthcare Ag | Use of cyclic acetals/ketals for improved penetration of active substances into cells and organs |
US20070270503A1 (en) * | 2003-04-02 | 2007-11-22 | Bayer Healthcare Ag | Penetration of Active Substances Into Cells and Organs |
WO2004087117A3 (en) * | 2003-04-02 | 2005-02-10 | Bayer Healthcare Ag | Use of cyclic acetals/ketals for improved penetration of active substances into cells and organs |
US7652071B2 (en) | 2003-04-02 | 2010-01-26 | Alpha-Biocare Gmbh | Penetration of active substances into cells and organs |
US8486375B2 (en) | 2003-04-28 | 2013-07-16 | Foamix Ltd. | Foamable compositions |
US9050253B2 (en) | 2003-08-04 | 2015-06-09 | Foamix Pharmaceuticals Ltd. | Oleaginous pharmaceutical and cosmetic foam |
US8486374B2 (en) | 2003-08-04 | 2013-07-16 | Foamix Ltd. | Hydrophilic, non-aqueous pharmaceutical carriers and compositions and uses |
US8795693B2 (en) | 2003-08-04 | 2014-08-05 | Foamix Ltd. | Compositions with modulating agents |
US9101662B2 (en) | 2003-08-04 | 2015-08-11 | Foamix Pharmaceuticals Ltd. | Compositions with modulating agents |
US9636405B2 (en) | 2003-08-04 | 2017-05-02 | Foamix Pharmaceuticals Ltd. | Foamable vehicle and pharmaceutical compositions thereof |
US8703105B2 (en) | 2003-08-04 | 2014-04-22 | Foamix Ltd. | Oleaginous pharmaceutical and cosmetic foam |
US8518378B2 (en) | 2003-08-04 | 2013-08-27 | Foamix Ltd. | Oleaginous pharmaceutical and cosmetic foam |
US8362091B2 (en) | 2003-08-04 | 2013-01-29 | Foamix Ltd. | Foamable vehicle and pharmaceutical compositions thereof |
US20110178162A1 (en) * | 2005-10-14 | 2011-07-21 | Medical University Of South Carolina | Targeting pax2 for the induction of defb1-mediated tumor immunity and cancer therapy |
US8795635B2 (en) | 2006-11-14 | 2014-08-05 | Foamix Ltd. | Substantially non-aqueous foamable petrolatum based pharmaceutical and cosmetic compositions and their uses |
US9682021B2 (en) | 2006-11-14 | 2017-06-20 | Foamix Pharmaceuticals Ltd. | Substantially non-aqueous foamable petrolatum based pharmaceutical and cosmetic compositions and their uses |
US9662298B2 (en) | 2007-08-07 | 2017-05-30 | Foamix Pharmaceuticals Ltd. | Wax foamable vehicle and pharmaceutical compositions thereof |
US10369102B2 (en) | 2007-08-07 | 2019-08-06 | Foamix Pharmaceuticals Ltd. | Wax foamable vehicle and pharmaceutical compositions thereof |
US8636982B2 (en) | 2007-08-07 | 2014-01-28 | Foamix Ltd. | Wax foamable vehicle and pharmaceutical compositions thereof |
US11103454B2 (en) | 2007-08-07 | 2021-08-31 | Vyne Therapeutics Inc. | Wax foamable vehicle and pharmaceutical compositions thereof |
US9439857B2 (en) | 2007-11-30 | 2016-09-13 | Foamix Pharmaceuticals Ltd. | Foam containing benzoyl peroxide |
US8518376B2 (en) | 2007-12-07 | 2013-08-27 | Foamix Ltd. | Oil-based foamable carriers and formulations |
US9161916B2 (en) | 2007-12-07 | 2015-10-20 | Foamix Pharmaceuticals Ltd. | Carriers, formulations, methods for formulating unstable active agents for external application and uses thereof |
US9795564B2 (en) | 2007-12-07 | 2017-10-24 | Foamix Pharmaceuticals Ltd. | Oil-based foamable carriers and formulations |
US8343945B2 (en) | 2007-12-07 | 2013-01-01 | Foamix Ltd. | Carriers, formulations, methods for formulating unstable active agents for external application and uses thereof |
US11433025B2 (en) | 2007-12-07 | 2022-09-06 | Vyne Therapeutics Inc. | Oil foamable carriers and formulations |
US8900553B2 (en) | 2007-12-07 | 2014-12-02 | Foamix Pharmaceuticals Ltd. | Oil and liquid silicone foamable carriers and formulations |
US9549898B2 (en) | 2007-12-07 | 2017-01-24 | Foamix Pharmaceuticals Ltd. | Oil and liquid silicone foamable carriers and formulations |
US8709385B2 (en) | 2008-01-14 | 2014-04-29 | Foamix Ltd. | Poloxamer foamable pharmaceutical compositions with active agents and/or therapeutic cells and uses |
US8609733B2 (en) | 2008-05-19 | 2013-12-17 | Massachusetts Institute Of Technology | Sensory-specific local anesthesia and prolonged duration local anesthesia |
US20110086922A1 (en) * | 2008-05-19 | 2011-04-14 | Massachusetts Institute Of Technology | Sensory-specific local anesthesia and prolonged duration local anesthesia |
WO2009143175A3 (en) * | 2008-05-19 | 2010-10-28 | Children's Medical Center Corporation | Sensory-specific local anesthesia and prolonged duration local anesthesia |
WO2009143175A2 (en) * | 2008-05-19 | 2009-11-26 | Children's Medical Center Corporation | Sensory-specific local anesthesia and prolonged duration local anesthesia |
US9249150B2 (en) | 2009-03-24 | 2016-02-02 | Proteus S.A. | Methods for purifying phycotoxins, pharmaceutical compositions containing purified phycotoxins, and methods of use thereof |
US8952152B2 (en) | 2009-03-24 | 2015-02-10 | Proteus S.A. | Methods for purifying phycotoxins, pharmaceutical compositions containing purified phycotoxins, and methods of use thereof |
US8957207B2 (en) | 2009-03-24 | 2015-02-17 | Proteus S.A. | Methods for producing phycotoxins |
US10213384B2 (en) | 2009-04-28 | 2019-02-26 | Foamix Pharmaceuticals Ltd. | Foamable vehicles and pharmaceutical compositions comprising aprotic polar solvents and uses thereof |
US10588858B2 (en) | 2009-04-28 | 2020-03-17 | Foamix Pharmaceuticals Ltd. | Foamable vehicles and pharmaceutical compositions comprising aprotic polar solvents and uses thereof |
US10363216B2 (en) | 2009-04-28 | 2019-07-30 | Foamix Pharmaceuticals Ltd. | Foamable vehicles and pharmaceutical compositions comprising aprotic polar solvents and uses thereof |
US9884017B2 (en) | 2009-04-28 | 2018-02-06 | Foamix Pharmaceuticals Ltd. | Foamable vehicles and pharmaceutical compositions comprising aprotic polar solvents and uses thereof |
US11219631B2 (en) | 2009-07-29 | 2022-01-11 | Vyne Pharmaceuticals Inc. | Foamable compositions, breakable foams and their uses |
US9167813B2 (en) | 2009-07-29 | 2015-10-27 | Foamix Pharmaceuticals Ltd. | Non surfactant hydro-alcoholic foamable compositions, breakable foams and their uses |
US9072667B2 (en) | 2009-07-29 | 2015-07-07 | Foamix Pharmaceuticals Ltd. | Non surface active agent non polymeric agent hydro-alcoholic foamable compositions, breakable foams and their uses |
US10350166B2 (en) | 2009-07-29 | 2019-07-16 | Foamix Pharmaceuticals Ltd. | Non surface active agent non polymeric agent hydro-alcoholic foamable compositions, breakable foams and their uses |
US9572775B2 (en) | 2009-07-29 | 2017-02-21 | Foamix Pharmaceuticals Ltd. | Non surfactant hydro-alcoholic foamable compositions, breakable foams and their uses |
US10092588B2 (en) | 2009-07-29 | 2018-10-09 | Foamix Pharmaceuticals Ltd. | Foamable compositions, breakable foams and their uses |
US10086080B2 (en) | 2009-10-02 | 2018-10-02 | Foamix Pharmaceuticals Ltd. | Topical tetracycline compositions |
US9675700B2 (en) | 2009-10-02 | 2017-06-13 | Foamix Pharmaceuticals Ltd. | Topical tetracycline compositions |
US8618081B2 (en) | 2009-10-02 | 2013-12-31 | Foamix Ltd. | Compositions, gels and foams with rheology modulators and uses thereof |
US10213512B2 (en) | 2009-10-02 | 2019-02-26 | Foamix Pharmaceuticals Ltd. | Topical tetracycline compositions |
US10238746B2 (en) | 2009-10-02 | 2019-03-26 | Foamix Pharmaceuticals Ltd | Surfactant-free water-free foamable compositions, breakable foams and gels and their uses |
US10265404B2 (en) | 2009-10-02 | 2019-04-23 | Foamix Pharmaceuticals Ltd. | Compositions, gels and foams with rheology modulators and uses thereof |
US8865139B1 (en) | 2009-10-02 | 2014-10-21 | Foamix Pharmaceuticals Ltd. | Topical tetracycline compositions |
US10322186B2 (en) | 2009-10-02 | 2019-06-18 | Foamix Pharmaceuticals Ltd. | Topical tetracycline compositions |
US10029013B2 (en) | 2009-10-02 | 2018-07-24 | Foamix Pharmaceuticals Ltd. | Surfactant-free, water-free formable composition and breakable foams and their uses |
US9849142B2 (en) | 2009-10-02 | 2017-12-26 | Foamix Pharmaceuticals Ltd. | Methods for accelerated return of skin integrity and for the treatment of impetigo |
US8871184B2 (en) | 2009-10-02 | 2014-10-28 | Foamix Ltd. | Topical tetracycline compositions |
US8992896B2 (en) | 2009-10-02 | 2015-03-31 | Foamix Pharmaceuticals Ltd. | Topical tetracycline compositions |
US10967063B2 (en) | 2009-10-02 | 2021-04-06 | Vyne Therapeutics Inc. | Surfactant-free, water-free formable composition and breakable foams and their uses |
US10463742B2 (en) | 2009-10-02 | 2019-11-05 | Foamix Pharmaceuticals Ltd. | Topical tetracycline compositions |
US10517882B2 (en) | 2009-10-02 | 2019-12-31 | Foamix Pharmaceuticals Ltd. | Method for healing of an infected acne lesion without scarring |
US10137200B2 (en) | 2009-10-02 | 2018-11-27 | Foamix Pharmaceuticals Ltd. | Surfactant-free water-free foamable compositions, breakable foams and gels and their uses |
US10610599B2 (en) | 2009-10-02 | 2020-04-07 | Foamix Pharmaceuticals Ltd. | Topical tetracycline compositions |
US10821187B2 (en) | 2009-10-02 | 2020-11-03 | Foamix Pharmaceuticals Ltd. | Compositions, gels and foams with rheology modulators and uses thereof |
US8945516B2 (en) | 2009-10-02 | 2015-02-03 | Foamix Pharmaceuticals Ltd. | Surfactant-free water-free foamable compositions, breakable foams and gels and their uses |
US10835613B2 (en) | 2009-10-02 | 2020-11-17 | Foamix Pharmaceuticals Ltd. | Compositions, gels and foams with rheology modulators and uses thereof |
US10946101B2 (en) | 2009-10-02 | 2021-03-16 | Vyne Therapeutics Inc. | Surfactant-free water-free foamable compositions, breakable foams and gels and their uses |
WO2011138678A3 (en) * | 2010-05-04 | 2016-05-26 | Foamix Ltd. | Compositions, gels and foams with rheology modulators and uses thereof |
US10881647B2 (en) | 2013-03-15 | 2021-01-05 | The Children's Medical Center Corporation | Neosaxitoxin combination formulations for prolonged local anesthesia |
US8975281B2 (en) | 2013-03-15 | 2015-03-10 | The Children's Medical Center Corporation | Neosaxitoxin combination formulations for prolonged local anesthesia |
US10314833B2 (en) | 2013-03-15 | 2019-06-11 | The Children's Medical Center Corporation | Neosaxitoxin combination formulations for prolonged local anesthesia |
US8975268B2 (en) | 2013-03-15 | 2015-03-10 | The Children's Medical Center Corporation | Neosaxitoxin combination formulations for prolonged local anesthesia |
US10849847B2 (en) | 2016-09-08 | 2020-12-01 | Foamix Pharamaceuticals Ltd. | Compositions and methods for treating rosacea and acne |
US10398641B2 (en) | 2016-09-08 | 2019-09-03 | Foamix Pharmaceuticals Ltd. | Compositions and methods for treating rosacea and acne |
US11324691B2 (en) | 2016-09-08 | 2022-05-10 | Journey Medical Corporation | Compositions and methods for treating rosacea and acne |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US3004894A (en) | Therapeutic composition comprising tetracycline and a dioxolane | |
US2515898A (en) | Procaine penicillin and therapeutic compositions | |
EP0602586B1 (en) | Stable pharmaceutical composition of fumagillol derivatives | |
ES2145115T4 (en) | INJECTABLE COMPOSITIONS BASED ON TAXANOS DERIVATIVES. | |
KR19990067603A (en) | Aqueous suspension of 9-hydroxyrisperidone fatty acid ester | |
JP4234198B2 (en) | Compounds for veterinary and medical applications | |
JP2012167132A (en) | FREEZE-DRIED PREPARATION OF N-[o-(p-PIVALOYLOXY BENZENESULFONYLAMINO)BENZOYL]GLYCINE MONOSODIUM SALT TETRAHYDRATE | |
DE102004063347A1 (en) | Ready-to-use gemcitabine solutions and gemcitabine solution concentrates | |
US2795528A (en) | Therapeutic composition containing a tetracycline and a phosphate other than orthophosphate | |
US3337400A (en) | Aqueous post-surgical injection by infiltration with a local anesthetic, a substantially water-insoluble, local anti-inflammatory gluco corticoid, and an antibiotic | |
US2619447A (en) | Injectable penicillin preparations | |
US5002940A (en) | Solid drug formulations and stable suspensions | |
EP1618894B1 (en) | Composition for injection | |
US2966442A (en) | Antibiotic compositions | |
US2518510A (en) | Stable injectable oil-pectin therapeutic compositions | |
US3900561A (en) | Pharmaceutical compositions | |
ES2215856T3 (en) | SOLUTION OF MONOSODIC SALT TETRAHYDRATE OF N- (O- (P-PIVALOYLOXIBENCENO-SULFONYLAMINE) BENZOIL) GLYCINE AND MEDICINAL PRODUCT CONTAINING THIS SOLUTION. | |
US2856329A (en) | Methods of administering steroid hormone solutions | |
US2791531A (en) | Erythromycin thiocyanate and compositions containing same | |
RU2023449C1 (en) | Method of stabilization of 4-ethyl-2-hydroxyimino-5-nitro-3-hexeneamide | |
HU191538B (en) | Process for producing pharmaceutical compositions containing acid additional salts of vinca-dimeres | |
US4039668A (en) | Corticoid-containing inhalants | |
US2472453A (en) | Streptomycin composition of reduced toxicity | |
US2676961A (en) | Procaine-penicillin preparation | |
US3737545A (en) | Alpha-aminobenzyl penicillins |