US3849569A - Composition containing procaine penicillin - Google Patents

Composition containing procaine penicillin Download PDF

Info

Publication number
US3849569A
US3849569A US32806373A US3849569A US 3849569 A US3849569 A US 3849569A US 32806373 A US32806373 A US 32806373A US 3849569 A US3849569 A US 3849569A
Authority
US
Grant status
Grant
Patent type
Prior art keywords
procaine
penicillin
base
preparations
non
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
Application number
Inventor
R Mead
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Glaxo Group Ltd
Original Assignee
Glaxo Group Ltd
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Grant date

Links

Images

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins
    • A61K31/41Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/425Thiazoles
    • A61K31/429Thiazoles condensed with heterocyclic ring systems
    • A61K31/43Compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula, e.g. penicillins, penems
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/16Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
    • A61K47/18Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/0012Galenical forms characterised by the site of application
    • A61K9/0041Mammary glands, e.g. breasts, udder; Intramammary administration

Abstract

1. A NON-AQUEOUS ANTIBIOTIC COMPOSITION FOR INTRAMAMMARY USE CONSISTING ESSENTIALLY OF FROM ABOUT 3.33%10% BY WEIGHT OF PROCAINE PENICILLIN G, FROM ABOUT 1%3% BY WEIGHT OF PROCAINE BASE AS STABILIZING AGENT FOR SAID PROCAINE PENICILLIN G AND FROM ABOUT 2%-3% OF POLYOXYETHYLENE SORBITAN MONOOLEATE IN A VEGETABLE OIL BASE.

Description

United States Patent 3,849,569 COMPOSITION CONTAINING PROCAINE lPENlCILLlN Robert James Mead, Barnard Castle, England, assignor to Glaxo Laboratories Limited, Greenford, Middlesex, England No Drawing. Continuation of application Ser. No. 106,912, Jan. 15, 1971, which is a continuation of application Ser. No. 837,980, Apr. 30, 1969, which in turn is a continuation of application Ser. No. 511,229, Dec. 2, 1965, all now abandoned. This application Jan. 30, 1973, Ser. No. 328,063 Claims priority, application Great Britain, Jan. 20, 1966, 50,579/ 66 Int. Cl. A61k 21/00 U.S. Cl. 424-271 1 Claim ABSTRACT OF THE DISCLOSURE There are disclosed non-aqueous pharmaceutical compositions containing a procaine penicillin, a non-ionic wetting agent and from 0.001% by weight of procaine base as a stabiliser for the procaine penicillin. The composition may also include a vegetable or mineral oil.

This application is a continuation of now abandoned application Ser. No. 106,912 filed Jan. 15, 1971, which is in turn a continuation of now abandoned application Ser. No. 837,980 filed Apr. 30, 1969, which is in turn a continuation of abandoned application Ser. No. 511,229 filed Dec. 2, 1965.

This invention relates to compositions containing procaine penicillins, and is particularly concerned with the stabilisation of procaine penicillins in such compositions which are non-aqueous and contain procaine penicillin antagonists. The invention is especially concerned with the stabilisation of compositions containing procaine penicillin G, although it also relates for example to the stabilisation of compositions containing procaine penicillin V.

It is known to incorporate procaine penicillin G into intramammary preparations adapted for use in the treatment of mastitis and associated diseases of the udder caused wholly or in part by penicillin sensitive organisms. The vehicles for such intramammary preparations are conveniently non-aqueous media including for example polyethylene glycols and/or other non-ionic wetting agents, if desired in admixture with vegetable or mineral oils. As is well known in the art such preparations generally contain of the order of from 10,000-300,000 units per millilitre (130% w./v.) of a procaine penicillin as exemplified by US. Pat. No. 2,728,704.

It may also be useful to incorporate into veterinary preparations of this type, a tracer substance which serves to identify milk from cows which have been treated with the preparations. The tracer substance may, for example,

be a suitable dye. In addition, the preparations may contain further antibiotics such as, for example, novobiocin and dihydrostreptomycin (either as such or in the form of pharmaceutical salts thereof e.g. sulphates).

Apart from intramammary preparations procaine penicillins may be incorporated into non-aqueous pharmaceutical compositions for human or veterinary medicine e.g. for topical, parenteral, or rectal administration. For example, it has been proposed to include procaine penicillin G in non-aqueous water-dispersable ointments for direct application to the skin or for use in preparations of the Tulle-gras type. Alternatively, procaine penicillins may be included in non-aqueous water-dispersable intramuscular or subcutaneous injectable preparations, or in suppositories or pessaries.

The potency stability of many non-aqueous waterdispersable pharmaceutical preparations containing procaine penicillin is not in general satisfactory, and our researches have shown that this instability is apparently due to the presence of substances which may be broadly described as non-ionic wetting agents, commonly used in such preparations.

It is an object of the present invention therefore to improve the stability of non-aqueous compositions containing a procaine penicillin and a nonionic wetting agent.

According to one feature of the present invention, there is provided a non-aqueous composition for use in human or veterinary medicine Which contains a procaine penicillin, a non-ionic wetting agent and procaine base as stabilising agent for the procaine penicillin.

According to a further feature of the present invention, there is provided a method of improving the stability of a non-aqueous human or veterinary composition containing a procaine penicillin and a non-ionic Wetting agent which method comprises incorporating into the said composition procaine base as stabilising agent for the procaine penicillin.

One particularly useful application of the method according to the invention is in the production of veterinary preparations as described above, adapted for use in the treatment of mastitis and associated diseases of the udder caused by penicillin sensitive organisms. As previously stated such preparations conveniently contain polyethylene glycols and/or other non-ionic wetting agents, which compounds as stated above in general unfavourably affect the stability of procaine penicillins. Examples of non-ionic Wetting agents of use in the veterinary preparations are as follows:

(a) Polyethylene glycols.

(b) Polyhydric alcohols, or their anhydrides, esterified with fatty acids, for example, sorbitan monostearate, propylene glycol monostearate, diglycol monostearate, mannitan mono-oleate, sorbitan sesquioleate, glyceryl monostearate, propylene glycol monooleate, propylene glycol monolaurate, diglycol monolaurate, diglycol rnonooleate, diglycol mono-palmitate, diglycol monoricinoleate, pentaerythritol mono-stearate, pentaerythritol distearate, pentaerythritol dioleate, pentaerythritol glycerol oleate, pentaerythritol dioleostearate, low-molecular polyoxyethylene oleate, glyceryl mono-groundnut acid ester, polyglyceryl monostearate, polyglyceryl-oleate, glycol monostearate, glyceryl mono-oleate, glyceryl mono-palmitate or low molecular polyoxyethylene monostearate.

(c) Polyoxyalkylene derivatives of esters of polyhydric alcohols such as hexitans, glycols or glycerol e.g. polyoxyethylene so-rbitan monostearate (Tween 60), polyoxyethylene propylene glycol monostearate, polyoxyethylene glycol monolaurate, polyoxyethylene glycol mono-oleate, polyoxyethylene glycol monostearate, polyoxyethylene glyceryl stearate, polyoxyethylene sorbitan monopalmitate, polyoxyethylene sorbitan monolanrate, polyoxyethylene sorbitan trioleate, or polyoxyethylene sorbitan monooleate (Tween (d) Fatty acid esters of polyethylene glycol, for ex ample polyethylene glycol 300 dilaurate, polyethylene glycol 300 monostearate, polyethylene glycol distearate and nonaethylene glycol mono-oleate, lower molecular polyglycol ricinoleate, lower molecular polyglycol monocaprate-caprylate, or lower molecular polyglycol monolaurate.

(e) Fatty alcohols condensed with ethylene oxide, e.g. polyethylene glycol monocetyl ether (Texofor A.I.P. Cetomacrogel 1,000 B.P.C.) and the material sold as Collone AC.

The polyhydric alcohols from which the above-mentioned non-ionic wetting agents are derived are also in general antagonistic to procaine penicillins. Thus, the method according to the invention is useful in the case of veterinary preparations and other compositions which contain the free polyhydric alcohols.

The veterinary preparations may contain other substances which can affect the stability of procaine penicillin e.g. certain tracer substances such as the dyes Edicol Supra Blue E.G.S. and Edicol Supra Green; antibiotics such as streptomycin and dihydro streptomycin, and therapeutic salts of antibiotics. While the present invention is principally concerned with reducing instability due to non-ionic wetting agents, the procaine base used as stabilising agent may also in part counteract the undesired effects of such other substances.

Veterinary preparations according to the invention may include mineral or vegetable oils. The mineral oils may be mixtures of hydrocarbon oils known in medicine as liquid parafiin and light liquid parafiin (or petroleum), preferably those of the British or United States pharmacopeias; the term also includes a mixture of one or more of the oils included under the terms liquid paraffin and light liquid parafiin with white or yellow soft parafiins and/or such compositions which simulate petroleum jellies and consist essentially of mixtures of hydrocarbons; examples of such last-mentioned compositions are those sold as Cosmojells 60, 70 and 80. By white or yellow soft parafiins is meant the purified and bleached, or unbleached mixtures of semisolid hydrocarbons specified under these terms in the British or United States pharmacopeias. Suitable vegetable oils include, for example, arachis, peanut, corn, cotton seed, sesame, soybean, raw linseed, palm and olive oils. The veterinary preparations may also conveniently contain thickening agents, for example beeswax, hydrogenated castor oil, hydrogenated peanut oil and soft and hard paraflins.

Also as is well known in the art veterinary preparations of the type disclosed above which also contain surface active agents, generally include such agents in an amount of the order of 0.5% as exemplified by U.S. Pat. No. 3,049,473.

The proportion of procaine base which is preferably used varies according to the type of composition concerned. For example, it has been found that intramammary preparations according to the invention having a mineral oil vehicle, in general should contain less procaine base than similar veterinary preparations accord ing to the invention having a vegetable oil vehicle. With preparations containing mineral oil, the use of too large amounts of procaine base may be undesirable. The optimum amount of procaine base for a given composition can be determined by simple experiment. Thus, for example, we have examined the effect of procaine base concentrations ranging from a minimum of 0.25% by weight up to a maximum of 10% by weight in intramammary preparations containing procaine penicillin G, Tween 80, beeswax and arachis oil. It has been shown that within this range the larger the amount of procaine base used, the better the stability of the procaine penicillin G. There is not, however, a straight-line relationship between concentration on the one hand and increase in stability on the other. It thus appears that very high concentrations of procaine base are of relatively little more value than somewhat lower concentrations, as the curve of procaine base concentration against degree of stabilisation tends to flatten out at high concentrations of procaine base. Also, it is generally the case that doubling of the concentration of non-ionic wetting agent (Tween 80) causes an increase in instability which is not completely counteracted by doubling the concentration of procaine base.

The proportion of procaine base in compositions ac cording to the invention is in general conveniently within the range of from 0.001% to 10% by weight of the composition. Concentrations of procaine base in the lower part of this range are particularly suitable for use in conjunction with intramammary preparations in which procaine base is only slightly soluble; and higher concentrations in preparations in which procaine base is very soluble. Examples of particularly preferred proportions of procaine base in intramammary preparations based on beeswax, arachis oil and 3% Tween are as follows:

1-3% by weight for a preparation containing 100,000 u.

procaine penicillin G per 3 g. dose.

0.5-2% by weight for a preparation containing 300,000

u. procaine penicillin G per 3 g. dose.

25% by weight for a preparation containing 100,000 u. procaine penicillin G and 1 g. dihydrostreptomycin per 3 g. dose.

Where the vehicle comprises mineral oil, then the proportion of procaine base may conveniently be from 0.01 to 1.0% by weight.

It will be appreciated that, whilst the method according to the present invention has been particularly described principally with reference to veterinary preparations, nevertheless it is also equally applicable to other compositions in human or animal medicine (e.g. pharmaceutical compositions for topical, parenteral or rectal administration) which contain a procaine penicillin in a non-aqueous base containing a non-ionic wetting agent.

The following examples illustrate the invention:

EXAMPLE 1.Intramammary preparation The following ingredients were introduced into a vessel fitted with a stirrer and closures which prevented the entry of micro-organisms:

G. Tween 60 30 Beeswax (white) Arachis oil to 1,000

These ingredients were heated at 150 C. for 1 hour and then cooled to room temperature with stirring.

880 g. of the vehicle prepared as described above were placed in a sterile 2 litre beaker and g. of procaine penicillin G and 20 g. of procaine base were added with stirring. The product was then refined with a high-speed stirrer to give a water-dispersable product containing 100,- 000 u./ g. of procaine penicillin.

In the following examples, the preparations were made by techniques analogous to those described in Example 1.

EXAMPLE 2 Procaine penicillin G, w/w 3.33 Procaine base, w/w 0.025 Vehicle to: w/w 100 Vehicle Tween 80, w/w 2.75 White soft paraffin, w/w 20 Liquid paraffin, to 100 EXAMPLE 3 Procaine penicillin G, w/w 3.33 Procaine base, w/w 2.0 Vehicle to: w/w 100 Vehicle:

Tween 80, w/w 2 Stearic acid, w/w 5 White soft paraffin, w/w 20 Arachis oil to, percent 100 EXAMPLE 4 Procaine penicillin G, w/w 3.33 Procaine base, w/w 2 Vehicle to: 100 Vehicle:

Tween 80, w/w 2 "Synthawax, w/w 5 Refined, winterised, deodourised cotton seed oil to, percent 100 Synthawax is a hardened castor oil consisting mainly of the triglyceride of 12-hydroxy stearic acid, prepared by the hydrogenation of castor oil.

EXAMPLE 5 Procaine penicillin G, w/w 3.33 Procaine base, w/w 2.0 Vehicle to: 100 Vehicle:

Tween 80, w/w 2 Cetostearyl alcohol, w/w 5 White soft paraffin, w/w 20 Arachis oil to, percent 100 EXAMPLE '6 Procaine penicillin G, w/w 3.33 Procaine base, w/w 2.0 Vehicle to: 100 Vehicle:

Polyethylene glycol 300, w/w 25 Polyethylene glycol 400, w/w 25 Polyethylene glycol 1000, w/w 50 After 12 months storage at 4 C. this formulation had lost 22.5% of its initial potency, whilst a similar formulation but with the procaine base omitted, had lost more than 80% of its potency.

At room temperature the formulation lost 15.5% of its initial potency in 18 days whilst a similar formulation with the procaine base omitted lost 77% of its potency.

EXAMPLE 7 Procaine penicillin G, W/w 3.33 Procaine base, w/w 2.0 Brilliant Blue F;C.F., w/w 4.167 Vehicle to: 100.0 Vehicle:

Tween 80, w/w 2.75 Beeswax, w/w 8.0 Arachis oil to, percent 100 Without procaine base in this formulation, the addition of the dye caused such rapid destruction of the procaine penicillin G that the preparation was considered to be of no commercial value.

6 EXAMPLE 8 Procaine penicillin G, w/w 10 Procaine base, w/w 2 Vehicle to: 100 Vehicle:

Polyethylene glycol 1000, w/w 30 Soft Paraffin, w/w

EXAMPLE 9 Procaine penicillin G, w/w 10 Procaine base, W/W 2 Vehicle to: Vehicle:

Polyethylene glycol 1000, w/w 30 Beeswax, w/w 10 Arachis oil to, percent 100 EX AMPLE 10 Procaine penicillin G, u 300,000 Sodium novobiocin, g. free acid 0.25 Procaine base, mg. 60 Vehicle (3% Tween 80 and 9% beeswax in arachis oil) to g. 3

I claim:

1. A non-aqueous antibiotic composition for intramammary use consisting essentially of from about 3.33%- 10% by weight of procaine penicillin G, from about 1%- 3% by weight of procaine base as stabilizing agent for said procaine penicillin G and from about 2%3% of polyoxyethylene sorbitan monooleate in a vegetable oil base.

References Cited UNITED STATES PATENTS 2,443,778 6/ 1948 Romansky 424--271 2,476,351 7/ 1949 Binkley 424-271 2,567,679 9/1951 Rhodehamel 424271 2,749,274 6/ 6 Buckwalter 424271 JEROME D. GOLDBERG, Primary Examiner UNITED STATES PATENT OFFICE CERTIFICATE OF CORRECTION Patent No. 3,849, 569 Dated November 19, 1974 Inventor(s) ROBERT JAMES MEAD It is certified that error appears in the above-identified patent and that said Letters Patent are hereby corrected as shown below:

Column 1, line 13, Jan. 20, 1966" should read Dec. 11, 1964 Column 1, line 14, "50,579/66" should read 50579/64 Signed and sealed this 15th day of April 1975.

a... t (LDQZ'iL) Attest:

C. DAI'W ILJTH C. T151301? Commissioner of Patents attesting Qffice-r and Trademarks FORM PO-105O (10-69) USCOMM-DC 6O376-P69 u.s. GOVERNMENT PRINTING OFFICE: 1969 o3ss-au.

Claims (1)

1. A NON-AQUEOUS ANTIBIOTIC COMPOSITION FOR INTRAMAMMARY USE CONSISTING ESSENTIALLY OF FROM ABOUT 3.33%10% BY WEIGHT OF PROCAINE PENICILLIN G, FROM ABOUT 1%3% BY WEIGHT OF PROCAINE BASE AS STABILIZING AGENT FOR SAID PROCAINE PENICILLIN G AND FROM ABOUT 2%-3% OF POLYOXYETHYLENE SORBITAN MONOOLEATE IN A VEGETABLE OIL BASE.
US3849569A 1965-12-02 1973-01-30 Composition containing procaine penicillin Expired - Lifetime US3849569A (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
US51122965 true 1965-12-02 1965-12-02
US3849569A US3849569A (en) 1965-12-02 1973-01-30 Composition containing procaine penicillin

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US3849569A US3849569A (en) 1965-12-02 1973-01-30 Composition containing procaine penicillin

Publications (1)

Publication Number Publication Date
US3849569A true US3849569A (en) 1974-11-19

Family

ID=26986195

Family Applications (1)

Application Number Title Priority Date Filing Date
US3849569A Expired - Lifetime US3849569A (en) 1965-12-02 1973-01-30 Composition containing procaine penicillin

Country Status (1)

Country Link
US (1) US3849569A (en)

Cited By (23)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4034099A (en) * 1974-03-29 1977-07-05 The Upjohn Company Compositions and method for treating mastitis in milk animals
US4525339A (en) * 1982-10-15 1985-06-25 Hoffmann-La Roche Inc. Enteric coated oral dosage form
EP0222712A2 (en) * 1985-11-08 1987-05-20 FATRO S.p.A: Veterinary compositions containing antimicrobial agents, and their use
WO2003077885A2 (en) * 2002-03-12 2003-09-25 Neurogesx, Inc. Free-base formulations of local anesthetics
WO2004032899A1 (en) * 2002-10-08 2004-04-22 Orchid Chemicals & Pharmaceuticals Ltd. Antibiotic formulation for intramammary administration in milking animals
US20060107870A1 (en) * 2004-11-19 2006-05-25 Drexell Barnes Ski wax formulation
US20140066524A1 (en) * 2009-10-02 2014-03-06 Foamix Ltd. Compositions, gels and foams with rheology modulators and uses thereof
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
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
US9439857B2 (en) 2007-11-30 2016-09-13 Foamix Pharmaceuticals Ltd. Foam containing benzoyl peroxide
US9492412B2 (en) 2002-10-25 2016-11-15 Foamix Pharmaceuticals Ltd. Penetrating pharmaceutical foam
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
US9636405B2 (en) 2003-08-04 2017-05-02 Foamix Pharmaceuticals Ltd. Foamable vehicle and pharmaceutical compositions thereof
US9662298B2 (en) 2007-08-07 2017-05-30 Foamix Pharmaceuticals Ltd. Wax 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
US9682021B2 (en) 2006-11-14 2017-06-20 Foamix Pharmaceuticals Ltd. Substantially non-aqueous foamable petrolatum based pharmaceutical and cosmetic compositions and their uses
US9713643B2 (en) 2002-10-25 2017-07-25 Foamix Pharmaceuticals Ltd. Foamable carriers
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

Cited By (29)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4034099A (en) * 1974-03-29 1977-07-05 The Upjohn Company Compositions and method for treating mastitis in milk animals
US4525339A (en) * 1982-10-15 1985-06-25 Hoffmann-La Roche Inc. Enteric coated oral dosage form
EP0222712A2 (en) * 1985-11-08 1987-05-20 FATRO S.p.A: Veterinary compositions containing antimicrobial agents, and their use
EP0222712A3 (en) * 1985-11-08 1987-11-19 Fatro S.P.A: Veterinary compounds containing antimicrobial agents, and their use
WO2003077885A2 (en) * 2002-03-12 2003-09-25 Neurogesx, Inc. Free-base formulations of local anesthetics
WO2003077885A3 (en) * 2002-03-12 2004-03-18 Arturo Angel Free-base formulations of local anesthetics
WO2004032899A1 (en) * 2002-10-08 2004-04-22 Orchid Chemicals & Pharmaceuticals Ltd. Antibiotic formulation for intramammary administration in milking animals
US9539208B2 (en) 2002-10-25 2017-01-10 Foamix Pharmaceuticals Ltd. Foam prepared from nanoemulsions and uses
US9713643B2 (en) 2002-10-25 2017-07-25 Foamix Pharmaceuticals Ltd. Foamable carriers
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
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
US9492412B2 (en) 2002-10-25 2016-11-15 Foamix Pharmaceuticals Ltd. Penetrating pharmaceutical foam
US9211259B2 (en) 2002-11-29 2015-12-15 Foamix Pharmaceuticals Ltd. Antibiotic kit and composition and uses thereof
US9636405B2 (en) 2003-08-04 2017-05-02 Foamix Pharmaceuticals Ltd. Foamable vehicle and pharmaceutical compositions thereof
US20060107870A1 (en) * 2004-11-19 2006-05-25 Drexell Barnes Ski wax formulation
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
US9439857B2 (en) 2007-11-30 2016-09-13 Foamix Pharmaceuticals Ltd. Foam containing benzoyl peroxide
US9795564B2 (en) 2007-12-07 2017-10-24 Foamix Pharmaceuticals Ltd. Oil-based foamable carriers and formulations
US9549898B2 (en) 2007-12-07 2017-01-24 Foamix Pharmaceuticals Ltd. Oil and liquid silicone 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
US9884017B2 (en) 2009-04-28 2018-02-06 Foamix Pharmaceuticals Ltd. Foamable vehicles and pharmaceutical compositions comprising aprotic polar solvents and uses thereof
US9572775B2 (en) 2009-07-29 2017-02-21 Foamix Pharmaceuticals Ltd. Non surfactant 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
US9675700B2 (en) 2009-10-02 2017-06-13 Foamix Pharmaceuticals Ltd. Topical tetracycline compositions
US20140066524A1 (en) * 2009-10-02 2014-03-06 Foamix Ltd. Compositions, gels and foams with rheology modulators 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

Similar Documents

Publication Publication Date Title
US3639575A (en) Silver ion gel compositions and method of using the same
US3674859A (en) Aqueous doxycycline compositions
US3636219A (en) Anticholinergic compositions containing certain thiazolines or imidazolines
US3384545A (en) Injectable aqueous emulsions of fat soluble vitamins
US3639574A (en) Stable hydrogen peroxide gels
Mergenhagen et al. Preparation and biological activities of endotoxins from oral bacteria
US5504068A (en) Topical preparations containing cyclosporin
US5403858A (en) New compositions containing taxane derivatives
US6251423B1 (en) Sterilizable paste product for topical application
US4788063A (en) Drug delivery system
US6235282B1 (en) Vaccinal fluid water-in-oil emulsions containing a metabolizable oil
US6100302A (en) Propofol formulation with enhanced microbial characteristics
US3743727A (en) Enhancing tissue penetration of certain antimicrobial agents with dimethyl sulfoxide
US5308621A (en) Ascorbic acid composition and transdermal administration method
US4435427A (en) Stable injectable β-carotene micellar solutions and their preparation
US5422109A (en) Fluid vaccines and active principle vehicles containing a metabolizable oil
US3252859A (en) Colloidal silica-oil composition and method of using same
US4016273A (en) Sustained release forms of certain oxazepines for parenteral administration
US2975099A (en) Polyethylene glycol suppository bases
US6177477B1 (en) Propofol formulation containing TRIS
US4153689A (en) Stable insulin preparation for nasal administration
US5061700A (en) Glyceryl acetate ointment vehicles
US6399087B1 (en) Propofol formulation with enhanced microbial inhibition
US3929985A (en) Anhydrous candicidin foam compositions
US5026556A (en) Compositions for the transdermal delivery of pharmaceutical actives