US3740420A - Pharmaceutical compositions with dimethyl sulfoxide - Google Patents
Pharmaceutical compositions with dimethyl sulfoxide Download PDFInfo
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- US3740420A US3740420A US00085696A US3740420DA US3740420A US 3740420 A US3740420 A US 3740420A US 00085696 A US00085696 A US 00085696A US 3740420D A US3740420D A US 3740420DA US 3740420 A US3740420 A US 3740420A
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- Prior art keywords
- dimethyl sulfoxide
- composition
- dmso
- compositions
- water
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- 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
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
-
- 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
- A61K31/095—Sulfur, selenium, or tellurium compounds, e.g. thiols
- A61K31/10—Sulfides; Sulfoxides; Sulfones
-
- 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
- A61K9/0014—Skin, i.e. galenical aspects of topical compositions
Definitions
- compositions and dosage forms for topical administration of dimethyl sulfoxide as a pharmaceutical are described, wherein the dimethyl sulfoxide concentration is between about 10% and about 90% and wherein diluents, together with dimethyl sulfoxide-soluble lipoidal thickening agents, water-dispersible thickening agents and emulsion-base thickening agents, are included in such compositions.
- Suppositories containing dimethyl sulfoxide (DMSO) are also described.
- Liquid formulations for topical application including at least 10% DMSO and an aqueous diluent in spray containers are also provided.
- compositions and dosage forms of dimethyl sulfoxide for use as a pharmaceutical to treat a variety of signs and symptoms, as will be dis cussed in detail herein.
- compositions of the present invention a considerable variety of medication and treatment exists.
- each has its limitations due to allergic response or potentially damaging side eifects, restricted spectrum of activity (effective only in limited types of disorders), restricted routes of administration, lack of individual response in a certain percentage of individuals, expense, etc. Therefore, additional agents are constantly being sought which can replace, supplement, or augment existing medication.
- topical application is a particularly advantageous route where treatment of a localized condition is desired since the effect of the agent may be concentrated at the area under treatment for 3,740,420 Patented June 19, 1973 rapid and specific results.
- Relatively few pharmaceuticals may be effectively applied topically to the skin and mucous membranes of the body cavities, particularly to obtain a response in disorders involving deeper tissues, structures and organs.
- compositions which are favorably tolerated and are substantially non-toxic at effective levels of administration. It is further desirable to provide pharmaceutical compositions which are effective in a wide range of conditions and which may be administered conveniently by topical administration.
- the present invention has as a primary object to provide such new, well-tolerated, substantially non-toxic pharmaceutical compositions and dosage forms which are effective for a wide range of conditions and which may be administered conveniently by the topical route.
- DMSO Dimethyl sulfoxide
- dimethyl sulfoxide has previously unrecognized valuable and extensive pharmaceutical activity. It has been found to be broadly useful in the treatment of damaged tissue, particularly as an anti-inflammatory agent, and as a stimulant to repair of the damaged tissue, as an analgesic agent, as a muscle relaxant, as an agent for treating vascular insufiiciency and as an agent for treating mental anxiety states and depression. It additionally has particular usefulness in relieving the collective signs and symptoms of certain specific syndromes, namely, respiratory distress, arthritis and burns.
- Dimethyl sulfoxide is rapidly rendered systemic in the body from all normal routes of administration and, importantly, it may be applied topically to the intact skin or mucous membrane to achieve highly unusual rapid absorption to the affected sites in the body.
- composition and dosage forms for topical administration have been developed which are especially adapted to utilize the pharmaceutical activity of dimethyl sulfoxide in an efficient manner, particularly in connection with its unique tissue penetration properties, while at the same time avoiding undue side effects.
- composition and dosage forms of the present invention in broad outline constitute topical formulations which comprise from about to about 90% by weight DMSO, an amount of a pharmaceutically acceptable diluent to minimize undesirable side affects consistent with effective penetration of DMSO and either a waterdispersible thickening agent, a DMSO-soluble lipoidal thickening agent, or an emulsion-base thickening agent to impart appropriate properties to the composition for effective and eflicient penetration by topical application to the skin or mucous membranes of a subject.
- Suppositories containing DMSO are also comprehended by the invention.
- liquid formulations for topical application comprising at least 10% by weight DMSO, an aqueous diluent and, optionally, thickening agents, etc., in spray containers.
- Such dosage forms are useful for topical application to prevent accidental spilling and undesired contact with the composition. They are particularly suitable for application to mucous membranes of various body orifices. They are also advantageous in providing a more uniform application to both dermal and mucous membrane surfaces.
- Other aspects of the compositions and dosage forms of this invention will become apparent from the detailed description which follows.
- COMPOSITION AND DOSAGE FORMS Dimethyl sulfoxide may be diluted with pharmaceutically acceptable diluents.
- Particularly useful are hydrophilic, DMSO-soluble or miscible diluents, which term, for the sake of convenience, is intended to include water, itself.
- Hydrophilic diluents generally lower the freezing point of the DMSO component (which, undiluted freezes at around 65 F.) so that the DMSO compositions remain unfrozen at temperatures normally encountered.
- dimethyl sulfoxide diluting dimethyl sulfoxide with such pharmaceutically acceptable soluble or miscible hydrophilic diluents, especially liquids such as water or glycerin, and including ethanol and saline solution, to form liquid, semisolid and solid formulations containing specified ranges of dimethyl sulfoxide concentration.
- pharmaceutically acceptable soluble or miscible hydrophilic diluents especially liquids such as water or glycerin, and including ethanol and saline solution
- pharmaceutical excipients may be employed to form advantageous dosage forms of dimethyl sulfoxide and, additionally, adjuvants may be incorporated in such formulations whereit is desired to combine the effects of dimethyl sulfoxide with another pharmaceutical.
- the dimethyl sulfoxide be applied in a pharmaceutically acceptable form, by which is meant that it be sufficiently purified so that it does not cause any untoward reaction or injury to the body of the subject from contaminants and the like.
- compositions containing at least about 50% dimethyl sulfoxide along with a minor amount of a pharmaceutically acceptable diluent, such as water, alcohol or glycerol, has been found to be uniquely suitable for skin application.
- a concentration of at least about 50% dimethyl sulfoxide has been found necessary to efficient, practical penetration of the skin barrier. Lower concentrations for this unique route may thus result in less than the desired effect.
- very high concentration of dimehyl sulfoxide as those substantially above 90%, the undesired side effects of local skin irritation and dehydration, erythema and urticaria increase markedly while no substantial increased benefit is obtained and the rate of DMSO penetration may actually be lessened.
- compositions containing from about 50% to about dimethyl sulfoxide and a pharmaceutical diluent, as exemplified by the 50%, 75% and 90% aqueous dimethyl sulfoxide compositions of following Example 2 have been found uniquely suitable and desirable.
- Dimethyl sulfoxide-glycerin solutions of 10% to 40% glycerin content are quite advantageous to minimize skin irritation due both to the dilution of the dimethyl sulfoxide and the emollient effect of the glycerin, which tends to soothe the irritation and skin dryness which may be caused by the dimethyl sulfoxide.
- compositions including dimethyl sulfoxide at a concentration of at least about 10%, preferably 20% to 40%, and including a pharmaceutical diluent, as for example water, alcohol or glycerol, are especially suitable.
- a pharmaceutical diluent as for example water, alcohol or glycerol
- Dilution of the dimethyl sulfoxide to a concentration of 90% and below is also advantageous in minimizing irritation to the mucous membranes.
- 10% to 90% concentrations of dimethyl sulfoxide are suitable for application to mucous membranes and particularly 10% to 90% water solutions.
- dimethyl sulfoxide may be formulated into highly convenient dosage forms with thickening agents, as illustrated in the examples which follow.
- Such forms include thickened solutions (paints) or lotions, ointments (including creams and gels), suppositories and the like.
- Thickened solutions or lotions, ointments and suppositories may be formed by incorporating with the dimethyl sulfoxide various gelling agents or other thickeners (viscosity increasers) which permit release of the dimethyl sulfoxide to the skin or mucous membranes upon application.
- gelling agents or other thickeners viscosity increasers
- These forms are advantageously employed to lessen the run-off from the skin that may occur with the more fluid composition forms, thereby permitting greater mobility for the patient immediately following treatment.
- they also permit more sustained contact of the dimethyl sulfoxide with the treated surfaces and more accurate and controlled dosing. Accidental spilling and undesired contact with the material can also be minimized with these formulations.
- water-dispersible thickening agents i.e., agents dispersible in water to form a homogenous distribution or solution
- these agents are readily compatible with water or other diluents to be formulated in the compositions and they may be readily washed from the skin following absorption into the skin of the DMSO.
- an emulsion base may be employed to impart the desired thickening effect, together with the emollient effect of the lipoid phase of the emulsion base, a better spreading and wetting effect and a retardation of the skin-drying effect of the DMSO.
- the DMSO is incorporated in the water phase thereof.
- a third category of thickening base which can also impart an emollient effect is provided by DMSO-soluble lipoidal thickening agents.
- the water-soluble thickening bases may utilize polyethylene glycols of different viscosities, depending upon the desired consistency and concentration of dimethyl sulfoxide to be incorporated, water-dispersible gums, carboxy vinyl polymers, methyl cellulose, sodium carboxy methyl cellulose, alginates and the like.
- Dimethyl sulfoxide may be added to the lotion, ointment or suppository base in varying amounts as desired, generally up to 50% or higher, depending on the consistency desired.
- the lotions, ointments and suppositories incorporating emulsion bases may contain the usual ingredients to provide the base, as for example a fatty alcohol such as cetyl alcohol, an emulsifier such as lauryl sulfate and water.
- a fatty alcohol such as cetyl alcohol
- an emulsifier such as lauryl sulfate and water.
- Another base may be formulated by combining equal weight amounts of stearic acid, cetyl alcohol, triethanolamine and glycerol monostearate together with water.
- DMSO-soluble lipoidal thickening agents for example lanolin, cocoa butter or glycerol monostearate, may be combined with DMSO and a diluent in proportions to obtain the desired consistency.
- a suppository form is highly advantageous, particularly for the treatment of hemorrhoids.
- the usual low melting gelling agents or other thickening agents may be employed for this purpose.
- the dimethyl sulfoxide concentration is usually 20% or below in this form but it may be higher, depending upon the strength of the gelling agent or other thickener.
- Agents such as polyethylene glycols of varying viscosities, glycerol monostearate and the like may be employed.
- a high viscosity polyethylene glycol, such as polyethylene glycol 4000, water and 20% dimethyl sulfoxide may be a suitable formulation.
- the pourable pharmaceutical dosages may be provided and dispensed in graduated containers or containers containing a given volume such as, for example, 1 cc., 2 cc., 5 cc., cc., 20 cc., 100 cc., 200 cc., or 500 cc.
- the containers With volumes of 20 cc. and above provide convenient multiple dosage forms and those containing a typical single dose, say from 0.5 gram to 20 grams of dimethyl sulfoxide, provide convenient unit dose forms.
- the practitioner need only open and dispense all or a determined part to a subject. In this way, the dosage may be ascertained and controlled readily by the practitioner.
- Squeeze tubes for lotions and ointments
- cotton stick applicators may all be utilized for topical application of the thickened compositions.
- the spraying and misting dosage forms of the invention constitute nasal spray bottles, aspirators, misting devices, aerosol bombs and other dispensing containers having liquid spray or mist dispensing means, which containers are charged with fluid formulations comprising at least 10% by weight DMSO and an aqueous diluent, and, optionally, thickening agents, physiological salts and the like.
- the water component is at least 10% by weight of the composition and preferably at least 50%.
- the compositions for this purpose are sufiiciently fluid to permit dispensing by spray or mist from the container. They also meet the previously described criteria for penetrability and avoidance of undue side effects.
- compositions and dosage forms of this invention are illustrative of the composition and dosage forms of this invention and techniques for their preparation:
- Example 1 Compositions of determined amounts Dimethyl sulfoxide is distilled at reduced pressure of under 25 mm. Hg in order to keep the temperature at 90 C. or less, and thereby prevent deterioration. A rapid distillation at 16 mm. Hg and 79 C. head temperature is satisfactory. An inert gas such as nitrogen is preferably used in the distillation process to displace other gases which may adversely affect the purity of the compound. The distilled liquid is filtered through activated charcoal and again distilled. The collected dimethyl sulfoxide is in a pharmaceutically acceptable form, and is transferred to cleaned bottle containers of 100, 200, and 500 ml. volumes. The bottles are stoppered with cleaned closures and identified.
- Example 2.Pharmaceutica1 solutions of dimethyl sulfoxide One hundred percent dimethyl sulfoxide in a pharmaceutically purified form is collected as shown in Example 1. Dilutions are made with distilled water and transferred to 500 cc. cleaned bottles which are then stoppered with cleaned closures. The dilutions provide separately bottled solutions containing dimethyl sulfoxide at concentrations of 10%, 20%, 50%, 75%, and The bottles are identified and are available for topical or oral application.
- Solutions of similar concentrations are also prepared using 0.9% saline (sodium chloride) as the diluent, in order to render the solution isotonic.
- the distilled water and saline solutions containing dimethyl sulfoxide at concentrations of 10% and 20% are Berkfield filtered to obtain a sterile form which is placed in cc. bottle containers.
- the bottles are stoppered.
- the sterilized solutions are checked for pyrogens with standard rabbit tests.
- Suppository and ointment compositions suitable for rectal, urethral or vaginal use, may be prepared with the following formulations:
- Acetylsalicylic acid grains/suppository 10 Carbowax polyethylene glycol 6000 parts 30 Carbowax polyethylene glycol 1540 do 30 Carbowax polyethylene glycol 600 do 30 Dimethyl sulfoxide do 10 Suppository (dimethyl sulfoxide concentrati0I1-2I%):
- Carbowax is a proprietary name of Union Carbide and the number following is an arbitrary designation related to the viscosity and melting point of the polyethylene glycol, the higher the number the higher the melt point and viscosity. For ointments, the compositions are desirably adjusted for a lower viscosity.
- DMSO-soluble, lipoidal thickening agents such as glycerol monostearate and cocoa butter may be used. They should be selected to melt at body temperature and release the dimethyl sulfoxide.
- concentration of dimethyl sulfoxide preferably may be up to 20%. Higher concentrations of 50% and above may also be employed if the thickening agent can thicken a higher quantity.
- the thickening agents may be melted in a water bath, the dimethyl sulfoxide and any other active ingredients added with mixing.
- the mix may be cooled to 50 C. and
- Example 4 Suppository composition The following ingredients are combined and the mixture is formed into a suppository which contains dimethyl sulfoxide at a concentration of about Carbowax gn1s 500 Water cc 50 Dimethyl sulfoxide cc- 100
- compositions for topical treatment Dilutions of DMSO with glycerin may be prepared by proportional mixing to obtain compositions with 10% to 40% glycerin.
- the glycerin serves as both a diluent and a thickening agent.
- Example 9.Spray composition forms DOSAGES AND ROUTES OF ADMINISTRATION The following is a general description of the manner of use of the compositions and dosage forms of this invention. For an additional discussion thereof which may be of use to the practitioner, reference is made to applicants copending application Serial No. 686,295, filed Nov. 28, 1967.
- Dimethyl sulfoxide can be effectively administered topically to the skin and mucous membranes of the various body cavities as by direct application or installation. Topical applications are of particular advantage where a local effect is desired. As discussed in detail under that heading, composition and dosage forms of dimethyl sulfoxide are provided which incorporate pharmaceutical diluents, ex cipients or adjuvants. For topical use, concentrations of from 10% to and above for application to mucous membranes and at least about 50% for dermal applications are indicated. The more advantageous concentrations and composition forms for particular routes of administration will also be discussed at a later point.
- the dosage and frequency of administration will be determined by the expertise of the attending practitioner who considers the nature and severity of the disorder, the area involved, the response desired or observed and the subject. Generally, as illustrated by the disclosure of application Ser. No. 686,295, the dosage may be as low as 0.01 gram per kilogram body weight and the optimum amount anywhere from around 0.02 to 0.05 up to 1.0 gram per kilogram of body weight per day or somewhat higher in a few instances. The average individual dose may be in the neighborhood of 0.1 to 0.2 gram per kg. body weight. However, the optimum dose will depend to a considerable extent upon the type and extent of the disorder and the mode of application.
- the treatment may be repeated once or twice daily, or even more frequently, until appropriate response is obtained or for the duration of the complaint. For some indications (such as many acute situations), only one or two applications involving a few cubic centimeters of dimethyl sulfoxide may be necessary while in chronic situations a more sustained regimen for a prolonged period or follow-up treatments may be called for. In any case, the optimum amount for a given disorder will depend upon the factors previously mentioned.
- the dimethyl sulfoxide compositions may be applied directly to the area involved, as by wetting skin or mucous membrane.
- Example 10 A 28-year-old female subject was seen with seborrheic dermatitis of the scalp. Thirty percent dimethyl sulfoxide in water with a lotion base was applied in four cc. volume three times daily for three days. At the end of one week, all local evidence of the dandruff was gone. The benefit in this chronic inflammation lasted for three weeks; the subject was treated at that time for recurrence, again with three days treatment with the same schedule as the first treatment. This time the benefit lasted for two months.
- topical application to a surface area rich in blood vessels is quite convenient.
- Higher concentrations are preferred for topical applications, such as at least 25 and more often, at least about 50%.
- the surface involved is thoroughly wetted.
- dimethyl sulfoxide solutions may be administered more frequently.
- Less frequent applications may be effectively made with solultions containing at least about 50% of dimethyl sulf- 0X1 e.
- a sterile pharmaceutical composition containing dimethyl sulfoxide as an essential, active pharmaceutical agent, suitable for topical application to achieve adequate tissue penetration of the dimethyl sulfoxide for a pharmaceutical effect which comprises between about 10% and about by weight of highly purified, substantially pyrogen-free dimethyl sulfoxide, a tissue irritation-decreasing amount of a first non-active component consisting of a pharmaceutically acceptable, non-thickening hydrophilic diluent and a second non-active component consisting of a pharmaceutically acceptable water-dispersible thickening agent in an amount to materially increase the viscosity of the composition and thus to retard run-01f following topical application thereof.
- composition as in claim 1 and wherein said diluent comprises a hydrophilic diluent selected from water, glycerin and ethyl alcohol in an amount of at least about by weight of said composition.
- composition as in claim 2 and wherein said composition is in unit dosage form containing between about 0.5 gram and grams of dimethyl sulfoxide.
- a composition as in claim 2 in the form of a lotion and containing a lotion base.
- a non-mobile, semisolid pharmaceutical composition containing dimethyl sulfoxide as an essential, active pharmaceutical agent, suitable for topical application to achieve adequate tissue penetration of the dimethyl sulfoxide for a pharmaceutical effect which comprises between about 10% and about 90% by weight of highly purified, substantially pyrogen-free dimethyl sulfoxide, a tissue irritation-decreasing amount of a pharmaceutically acceptable hydrophilic diluent selected from water, glycerin and ethyl alcohol and a pharmaceutically acceptable water-dispersible thickening agent, capable of releasing the dimethyl sulfoxide at body temperature, in an amount sufiicient to render said composition semisolid.
- a pharmaceutically acceptable hydrophilic diluent selected from water, glycerin and ethyl alcohol and a pharmaceutically acceptable water-dispersible thickening agent
- composition as in claim 8 in the form of a suppository.
- composition as in claim 8 wherein said diluent comprises water in an amount of at least about 10% by weight of said composition.
- a pharmaceutical composition containing dimethyl sulfoxide as an essential, active pharmaceutical agent, suitable for topical application to achieve adequate tissue penetration of the dimethyl sulfoxide for a pharamceutical effect which comprises between about 10% and about 90% by weight of a highly purified, substantially pyrogen-free dimethyl sulfoxide and an emulsion base consisting of an emulsifying agent, a lipoid phase and an aqueous phase, said DMSO being incorporated in said aqueous phase, siad emulsion base present in an amount to materially increase the viscosity of the composition and thus to retard run-off following topical application thereof.
- a sterile pharmaceutical composition containing dimethyl sulfoxide as an essential, active pharmaceutical agent, suitable for topical application to achieve adequate tissue penetration of the dimethyl sulfoxide for a pharmaceutical effect which comprises between about 10% and about by weight of highly purified, substantially pyrogen-free dimethyl sulfoxide, a tissue irritation-decreasing amount of a pharmaceutically acceptable hydrophilic diluent and a pharmaceutically acceptable dimethyl sulfoxide-soluble lipoidal thickening agent in an amount to materially increase the viscosity of the composition and thus to retard run-off following topical application thereof.
- a suppository containing dimethyl sulfoxide as an essential, active pharmaceutical agent, suitable for topical application to body cavities to achieve adequate tissue penetration of the dimethyl sulfoxide for a pharmaceutical effect which comprises a suppository base capable of releasing dimethyl sulfoxide when the suppository is administered and an effective amount of dimethyl sulfoxide to achieve a pharmaceutical effect.
- a container provided with liquid spray-dispensing means and containing a fluid, sprayable composition which comprises an amount of DMSO elfective to enhance external membrane penetration of said agent and comprising at least about 10% by weight of said composition and an aqeuous diluent comprising water in a concentration of at least about 10% by weight of said composition.
- a container as in claim 19 and wherein said DMSO in the composition charged therein comprises at least about 50% by weight of said composition.
- a container as in claim 19 and wherein the composition therein contains at least about 50% by weight of water.
Abstract
Description
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
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US68629567A | 1967-11-28 | 1967-11-28 | |
US8569670A | 1970-10-30 | 1970-10-30 |
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US3740420A true US3740420A (en) | 1973-06-19 |
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US00085696A Expired - Lifetime US3740420A (en) | 1967-11-28 | 1970-10-30 | Pharmaceutical compositions with dimethyl sulfoxide |
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Cited By (26)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2464068A1 (en) * | 1979-08-30 | 1981-03-06 | Herschler Robert | COMPOSITIONS BASED ON DIMETHYLSULFOXIDE AND THEIR APPLICATIONS, IN PARTICULAR THERAPEUTICS |
US4543964A (en) * | 1983-04-21 | 1985-10-01 | Breneman James C | Method for testing for immune responses to food |
US4575515A (en) * | 1984-05-14 | 1986-03-11 | Clark Pharmaceutical Laboratories Ltd. | Pharmaceutical solutions comprising dimethyl sulfoxide |
US4835191A (en) * | 1984-05-01 | 1989-05-30 | Biegeleisen Ken P | Methods for prevention of post-inflammatory hyperpigmentation |
US5059603A (en) * | 1989-06-12 | 1991-10-22 | Centuries Laboratories, Inc. | Method and composition for treating impotence |
US20060159711A1 (en) * | 2003-02-21 | 2006-07-20 | Yukiko Inamoto | Therapeutic agent for hemorrhoidal disease |
US20060281822A1 (en) * | 2005-04-20 | 2006-12-14 | Cardinal Associates, Inc. | Treatment and prevention of elevated homocysteine |
US20080242704A1 (en) * | 2005-04-04 | 2008-10-02 | Ab Science | Substituted Oxazole Derivatives and their Use as Tyrosine Kinase Inhibitors |
US20080255141A1 (en) * | 2002-08-02 | 2008-10-16 | Ab Science | 2-(3-aminoaryl) amino-4-aryl-thiazoles and their use as c-kit inhibitors |
US20100113471A1 (en) * | 2003-10-23 | 2010-05-06 | Ab Science | 2-Aminoaryloxazole compounds as tyrosine kinase inhibitors |
US7955418B2 (en) | 2005-09-12 | 2011-06-07 | Abela Pharmaceuticals, Inc. | Systems for removing dimethyl sulfoxide (DMSO) or related compounds or odors associated with same |
WO2011086085A1 (en) | 2010-01-12 | 2011-07-21 | Ab Science | Thiazole and oxazole kinase inhibitors |
WO2011092273A1 (en) | 2010-01-28 | 2011-08-04 | Ab Science | Treatment of gist with masitinib |
US20110201620A1 (en) * | 2002-08-02 | 2011-08-18 | Ab Science | 2-(3-aminoaryl) amino-4-aryl-thiazoles and their use as c-kit inhibitors |
US20110203583A1 (en) * | 2005-09-12 | 2011-08-25 | Abela Pharmaceuticals, Inc. | Methods for facilitating use of dimethyl sulfoxide (dmso) by removal of same, related compounds, or associated odors |
WO2013014170A1 (en) | 2011-07-27 | 2013-01-31 | Ab Science | Oxazole and thiazole derivatives as selective protein kinase inhibitors (c-kit) |
US8435224B2 (en) | 2005-09-12 | 2013-05-07 | Abela Pharmaceuticals, Inc. | Materials for facilitating administration of dimethyl sulfoxide (DMSO) and related compounds |
US8480797B2 (en) | 2005-09-12 | 2013-07-09 | Abela Pharmaceuticals, Inc. | Activated carbon systems for facilitating use of dimethyl sulfoxide (DMSO) by removal of same, related compounds, or associated odors |
US20150126606A1 (en) * | 2006-10-17 | 2015-05-07 | Hznp Limited | Diclofenac topical formulation |
US9370501B2 (en) | 2009-03-31 | 2016-06-21 | Hznp Limited | Treatment of pain with topical diclofenac |
EP3053920A1 (en) | 2015-02-05 | 2016-08-10 | AB Science | Compounds with anti-tumoral activity |
US9427419B2 (en) | 2005-09-12 | 2016-08-30 | Abela Pharmaceuticals, Inc. | Compositions comprising dimethyl sulfoxide (DMSO) |
EP3144307A1 (en) | 2015-09-18 | 2017-03-22 | AB Science | Novel oxazole derivatives that inhibit syk |
US9839609B2 (en) | 2009-10-30 | 2017-12-12 | Abela Pharmaceuticals, Inc. | Dimethyl sulfoxide (DMSO) and methylsulfonylmethane (MSM) formulations to treat osteoarthritis |
US10053455B2 (en) | 2014-03-24 | 2018-08-21 | Ab Science | Diazaspiroalkaneone-substituted oxazole derivatives as spleen tyrosine kinase inhibitors |
US10398656B1 (en) * | 2018-05-21 | 2019-09-03 | Veloce Biopharma, Llc | Compositions and methods for the treatment of viral skin disease |
-
1970
- 1970-10-30 US US00085696A patent/US3740420A/en not_active Expired - Lifetime
Cited By (53)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4296104A (en) * | 1979-08-30 | 1981-10-20 | Herschler R J | Therapeutic dimethyl sulfoxide composition and methods of use |
FR2464068A1 (en) * | 1979-08-30 | 1981-03-06 | Herschler Robert | COMPOSITIONS BASED ON DIMETHYLSULFOXIDE AND THEIR APPLICATIONS, IN PARTICULAR THERAPEUTICS |
US4543964A (en) * | 1983-04-21 | 1985-10-01 | Breneman James C | Method for testing for immune responses to food |
US4835191A (en) * | 1984-05-01 | 1989-05-30 | Biegeleisen Ken P | Methods for prevention of post-inflammatory hyperpigmentation |
US4575515A (en) * | 1984-05-14 | 1986-03-11 | Clark Pharmaceutical Laboratories Ltd. | Pharmaceutical solutions comprising dimethyl sulfoxide |
US4652557A (en) * | 1984-05-14 | 1987-03-24 | Clark Pharmaceutical Laboratories Ltd. | Pharmaceutical solutions comprising dimethyl sulfoxide |
US5059603A (en) * | 1989-06-12 | 1991-10-22 | Centuries Laboratories, Inc. | Method and composition for treating impotence |
US20110201620A1 (en) * | 2002-08-02 | 2011-08-18 | Ab Science | 2-(3-aminoaryl) amino-4-aryl-thiazoles and their use as c-kit inhibitors |
US8993573B2 (en) | 2002-08-02 | 2015-03-31 | Ab Science | 2-(3-aminoaryl) amino-4-aryl-thiazoles and their use as c-kit inhibitors |
US8835435B2 (en) | 2002-08-02 | 2014-09-16 | Ab Science | 2-(3-aminoaryl) amino-4-aryl-thiazoles and their use as c-kit inhibitors |
US8450302B2 (en) | 2002-08-02 | 2013-05-28 | Ab Science | 2-(3-aminoaryl) amino-4-aryl-thiazoles and their use as c-kit inhibitors |
US20080255141A1 (en) * | 2002-08-02 | 2008-10-16 | Ab Science | 2-(3-aminoaryl) amino-4-aryl-thiazoles and their use as c-kit inhibitors |
US8183232B2 (en) * | 2003-02-21 | 2012-05-22 | Teikoku Seiyaku Co., Ltd. | Therapeutic agent for hemorrhoidal disease |
US20060159711A1 (en) * | 2003-02-21 | 2006-07-20 | Yukiko Inamoto | Therapeutic agent for hemorrhoidal disease |
US20100113471A1 (en) * | 2003-10-23 | 2010-05-06 | Ab Science | 2-Aminoaryloxazole compounds as tyrosine kinase inhibitors |
US8110591B2 (en) | 2003-10-23 | 2012-02-07 | Ab Science | 2-aminoaryloxazole compounds as tyrosine kinase inhibitors |
US8658659B2 (en) | 2005-04-04 | 2014-02-25 | Ab Science | Substituted oxazole derivatives and their use as tyrosine kinase inhibitors |
US20080242704A1 (en) * | 2005-04-04 | 2008-10-02 | Ab Science | Substituted Oxazole Derivatives and their Use as Tyrosine Kinase Inhibitors |
US20060281822A1 (en) * | 2005-04-20 | 2006-12-14 | Cardinal Associates, Inc. | Treatment and prevention of elevated homocysteine |
US8298320B2 (en) | 2005-09-12 | 2012-10-30 | Abela Pharmaceuticals, Inc. | Systems for removing dimethyl sulfoxide (DMSO) or related compounds, or odors associated with same |
US9427419B2 (en) | 2005-09-12 | 2016-08-30 | Abela Pharmaceuticals, Inc. | Compositions comprising dimethyl sulfoxide (DMSO) |
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