US3463852A - Treating allergies with steroids of the pregnane series - Google Patents
Treating allergies with steroids of the pregnane series Download PDFInfo
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- US3463852A US3463852A US520675A US3463852DA US3463852A US 3463852 A US3463852 A US 3463852A US 520675 A US520675 A US 520675A US 3463852D A US3463852D A US 3463852DA US 3463852 A US3463852 A US 3463852A
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- steroids
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- 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
- A61K31/60—Salicylic acid; Derivatives thereof
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- 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
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/42—Phosphorus; Compounds thereof
Definitions
- This invention relates to pharmaceutical compositions comprising certain selected steroids of the pre-gnane series which are useful in eliciting an anti-allergy effect, and to processes for making and using such compositions.
- the invention sought to be patented in its composition aspect is described as residing in the concept of a pharmaceutical formulation containing as an essential active ingredient, a therapeutic quantity of 6a-fiuoro-16-methyl- 1,4-pregnadiene-17u,2l-diol-3,20-dione, or the 21-pharmaceutically acceptable esters thereof, having between the 9- and ll-positions a member of the group consisting of single and double bonds.
- the invention sought to be patented in its process aspect is described as residing in the concept of using the tangible embodiment of a pharmaceutical formulation containing the steroid component described above, by administering said formulation to a patient for the application of anti-allergy therapy.
- tangible embodiments of the invention as represented by the essential active ingredient described above possess the heretofore unknown applied use characteristics of exerting an anti-allergy response in mammals, as determined by standard pharmacological evaluation and concomitantly at the therapeutic dose exhibit essentially no glucoor mineralo-corticoid side effects normally associated with adrenocortical hormones.
- ester means those esters of adrenocortical hormones which are known to modify the parent steroid only in degree by altering solubility characteristics, metabolic characteristics and the like. Included within the term are esters of saturated hydrocarbon carboxylic acids having up to 12 carbon atoms, which may be straight chain, branched chain, cyclic or combinations thereof and which may be monoor polycarboxylic acids.
- esters are: Alkanoyl esters, of which acetate is most common, but including formate, propionate, butyrate, tbutyl acetate, trimethyl-acetate, and caproate; cyclic esters like cyclopentylpropionate, benzoa te, cyclohexylcarboxylate; neutral and acid esters of polybasic acids like succinic, maleic, malic, tartaric, phthalic, and the like.
- the term also includes esters of polybasic inorganic acids like sulfate or phosphate, the latter preferably as a dihydrogen phosphate.
- the polybasic organic and inorganic esters are generally used in the form of their metal salts, preferably sodium, which are prepared in the manner fully described in the art.
- Adrenocortical hormones both natural and synthetic, such as cortisone, hydrocortisone, prednisone, prednisolone, dexamethasone, triamcinolone and the like have been used to treat certain allergic conditions like bronchial asthma, skin disorders (psoriasis), contact dermatitis 3,463,852 Patented Aug. 26, 1969 brought about by allergens (poison ivy), and other manifestations of allergic origin. Therapy with these anti-inflammatory steroids has been somewhat satisfactory in the results achieved, however the principal drawback to the use of such agents is the concomitant production of varying degrees of side effects normally associated with adrenocortical hormones.
- Antihistamines have to some extent been successfully used in treating some of the allergic manifestations noted above. However, in bronchial asthma, for example, the use of antihistamines is contraindicated while in others, like psoriasis, they are ineffectual.
- the essential active ingredients of the tangible embodiment of this invention although steroids, and related to the adrenocortical hormones mentioned above, possess the advantageous anti-allergic properties, but their glucocorticoid and mineralocorticoid effects are essentially nonexistent at the therapeutic dose level. These steroid compounds therefore possess all the advantages of steroids with regard to anti-allergy treatment with practically none of the undesirable adrenocorticoid effects.
- the therapeutic ratio of anti-allergy dose to the dose required to produce undesirable side effects is extremely favorable, leading to the conclusion that for the first time a true separation of these properties has been discovered in steroids.
- mice The anti-allergy effects were first determined in mice by standard pharmacological evaluation. In this test,
- the test animal is sensitized with horse serum and serum challenge generally results in death to untreated animals.
- the steroids being tested are administered intramuscularly eighteen hours prior to the anaphylactic challenge. Observations are then made on the degree of protection afforded in groups of animals, each group receiving varying dosages of different compounds. Only those compounds which provided significant protection at a dose of about 50 mg./kg. were considered of value.
- test compounds then were submitted to the standard adrenocorticoid evaluation, such as the granulona pouch test, thymus involution test, depression of circulating eosinphiles test and the like and the dose required to elicit a positive response in these tests was compared with the dose required to elicit the aforedescribed antiallergy (or anti-anaphylactic effect).
- the selected steroids claimed herein in the form of pharmaceutical formulations uniquely exhibited a separation of properties resulting in an unobvious and extremely valuable therapeutic ratio of anti-allergic dose to adrenocorticoid dose.
- the effective dosage of the steroid compounds described herein depends upon the severity, the stage and the individual characteristics of each case and will be determined by an attending veterinarian or physician. Generally a dosage range of from about 0.1 to about 3.0 mg. per kg. of body weight per day constitutes the overall range.
- the steroids described herein are preferably administered orally in the form of tablets, capsules, elixers, solutions, sprays and the like.
- a particularly advantageous form for utilization in asthmatic conditions is as an aerosol spray taken directly into the mouth so that direct and intimate contact with lung tissue is achieved.
- Spray formulations may be conveniently administered nasally.
- Other modes of administration are via the topical and opthalmic route utilizing appropriate dosage forms such as solutions, ointments, and the like.
- parenteral administration either intramuscular or intravenous, may be called for such as extemporaneous treatment of anaphylactic shock.
- Dosage forms adaptable for such administration are sterile solutions and suspensions of the particular steroids.
- soluble esters of the unique steroids described herein are represented by the 21-phosphates in the form of monoor di-sodium salts, or the sodium salt of a 21-hemisuccinate. These salts and in particular the latter, are conveniently prepared in situ in the presence of a buffering agent which will establish a pH between about 6.5 and about 8.0.
- a preferred method for preparing such an ester is to prepare an aqueous solution of the 21-hemisuccinate in aqueous alkali in the presence of sodium dihydrogen phosphate and lyophilizing after sterilization by special filtration according to the method described in US. Patent No. 3,193,459. There is thus obtained a sterile water-soluble powder consisting of the sodium salt of the 21-hemisuccinate of, in the case of the preferred species, 6a-fluoro-16rx-methyl-1,4,9(11)- pregnatriene-17a,21-diol-3,20-dione.
- the pharmaceutical formulations generally described above may also include other therapeutic agents such as adrenocortical steroids, antihistamines, antibiotics, and the like, the composition of which will be regulated by the condition being treated.
- the foregoing examples provide tablets for oral use 1n the treatment of allergic conditions.
- the quantity of steroid may be increased to about 30 mg. per tablet.
- EXAMPLE 4 Nasal spray Mg./ml. 60 fluoro-l6wmethyl-l,4-pregnadiene-l7a,21-diol- 3,20-dione-21-acetate 10.0 Chlorpheniramine gluconate 3.0 D-sorbitol 43.0 Benzalkonium chloride, U.S.P. 0.25 Distilled water, to make 1.0 ml.
- Dichlorodifluoromethane Dichlorotetrafiuoroethane (50:
- the foregoing formation is administered through a metered valve designed to deliver 50 microliters per spray.
- EXAMPLE 8 Lyophilized powder for intravenous injection of aqueous solution Mg./m1. of reconstituted solution 6m fiuoro16a-methyl-1,4,9( l 1)-pregnatriene-1'7a,
- the active ingredients have been indicated to be 6u-fiuoro-l6a-methyl-l,4,9(l1)- pregnatriene-l7ec,2l-diol-3,20dione or the corresponding 9,11-dihydro analogs either in the form of their free 21-01 or as certain selected esters thereof. It is to be understood that these examples have been presented for the purpose of lilustration only and that the other steroids and the equivalents thereof mentioned herein as possessing the unique separation of properties described heretofore may be used equally.
- the concentration of the 0 active ingredient will be such that an amount of com position which can be conveniently administered during each treatment will contain a suflicient quantity of such active ingredient which Will elicit an appropriate and proper therapeutic response.
- a method of eliciting an anti-allergic effect in mammals which comprises administering to a mammal having an allergic disorder a therapeutically effective quantity of a compound selected from the group consisting of 60afluoro 16 methyl 1,4,9(11) pregnatriene 17,21- diol 3,20 dione, 6a fluoro 16 methyl 1,4 pregnadiene-17a,21-diol-3,20-dione and the C-21-pharm-aceutically acceptable esters thereof.
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Inorganic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
United States Patent US. Cl. 424-243 6 Claims ABSTRACT OF THE DISCLOSURE This invention relates to pharmaceutical compositions comprising 6u-fiuoro-16-methyl-1,4,9( l1) pregnatriene- 17a,21-diol-3,20-dione, 6u-fiuoro-16-methyl-L4 pregnadiene-17a,21-diol-3,20-dione and the 21-pharmaceutically acceptable esters thereof, and to methods for the use thereof in eliciting an anti-allergic effect.
This invention relates to pharmaceutical compositions comprising certain selected steroids of the pre-gnane series which are useful in eliciting an anti-allergy effect, and to processes for making and using such compositions.
The invention sought to be patented in its composition aspect is described as residing in the concept of a pharmaceutical formulation containing as an essential active ingredient, a therapeutic quantity of 6a-fiuoro-16-methyl- 1,4-pregnadiene-17u,2l-diol-3,20-dione, or the 21-pharmaceutically acceptable esters thereof, having between the 9- and ll-positions a member of the group consisting of single and double bonds.
The invention sought to be patented in its process aspect is described as residing in the concept of using the tangible embodiment of a pharmaceutical formulation containing the steroid component described above, by administering said formulation to a patient for the application of anti-allergy therapy.
The tangible embodiments of the invention as represented by the essential active ingredient described above possess the heretofore unknown applied use characteristics of exerting an anti-allergy response in mammals, as determined by standard pharmacological evaluation and concomitantly at the therapeutic dose exhibit essentially no glucoor mineralo-corticoid side effects normally associated with adrenocortical hormones.
As used herein the term pharmaceutically acceptable ester means those esters of adrenocortical hormones which are known to modify the parent steroid only in degree by altering solubility characteristics, metabolic characteristics and the like. Included within the term are esters of saturated hydrocarbon carboxylic acids having up to 12 carbon atoms, which may be straight chain, branched chain, cyclic or combinations thereof and which may be monoor polycarboxylic acids. Representative of these esters are: Alkanoyl esters, of which acetate is most common, but including formate, propionate, butyrate, tbutyl acetate, trimethyl-acetate, and caproate; cyclic esters like cyclopentylpropionate, benzoa te, cyclohexylcarboxylate; neutral and acid esters of polybasic acids like succinic, maleic, malic, tartaric, phthalic, and the like. The term also includes esters of polybasic inorganic acids like sulfate or phosphate, the latter preferably as a dihydrogen phosphate. The polybasic organic and inorganic esters are generally used in the form of their metal salts, preferably sodium, which are prepared in the manner fully described in the art.
Adrenocortical hormones, both natural and synthetic, such as cortisone, hydrocortisone, prednisone, prednisolone, dexamethasone, triamcinolone and the like have been used to treat certain allergic conditions like bronchial asthma, skin disorders (psoriasis), contact dermatitis 3,463,852 Patented Aug. 26, 1969 brought about by allergens (poison ivy), and other manifestations of allergic origin. Therapy with these anti-inflammatory steroids has been somewhat satisfactory in the results achieved, however the principal drawback to the use of such agents is the concomitant production of varying degrees of side effects normally associated with adrenocortical hormones. At the therapeutic dose required for anti-allergic effects of such known adrenocortical hormones, the undesirable side effects are patently existent. These effects are manifest by, for example, adrenal suppression, nitrogen and calcium loss, alteration in fat metabolism leading to abnormal deposition of fat resulting in the symptom known as buffalo hump.
Antihistamines have to some extent been successfully used in treating some of the allergic manifestations noted above. However, in bronchial asthma, for example, the use of antihistamines is contraindicated while in others, like psoriasis, they are ineffectual.
The essential active ingredients of the tangible embodiment of this invention, although steroids, and related to the adrenocortical hormones mentioned above, possess the advantageous anti-allergic properties, but their glucocorticoid and mineralocorticoid effects are essentially nonexistent at the therapeutic dose level. These steroid compounds therefore possess all the advantages of steroids with regard to anti-allergy treatment with practically none of the undesirable adrenocorticoid effects. The therapeutic ratio of anti-allergy dose to the dose required to produce undesirable side effects is extremely favorable, leading to the conclusion that for the first time a true separation of these properties has been discovered in steroids.
The aforementioned separation of properties appears to be unique with fia-fluoro-l6-methyl-1,4-pregnadiene- 17u,21-diol-3,20-dione having between the 9- and 11- positions a member of the group consisting of single and double bonds (and the ZI-pharmaceutically,acceptable esters thereof), and a limited number of hereinafter disclosed equivalents. The methyl group in the 16-position may be in either the a or ,8 configuration, however a more favorable effect is elicited with an a-methyl group.
It is thus apparent that the unique action is exhibited by a very limited group of compounds which in their free 21-01 form may be described as the 6ot-fluoro-l6amethyl and 6m-fiuoro-16/3-methyl analogs of 1,4-pregnadiene-l7a,21-diol-3,20-dione and l,4,9(1l)-pregnatriene- 17a,21-diol-3,20-dione. Any material variation from these structures, except for the equivalents hereinafter noted, results in diminution or elimination of the anti-allergic properties or a change in the separation of anti-allergic properties from ardenocortical properties in a manner that the latter becomes manifest at the therapeutic dose. For example, saturating the double bond in the 1,2-position, epimerizing the 6-substituent, or eliminating either or both substituents at the 6- and 16-positions results in compounds having little or no value. It has been determined that the structure is somewhat critical in that there must be present in the pregnane nucleus a 3-keto-1,4-diene system, the cortical side chain represented by 20-keto-l7a,2l-diol on the two-carbon chain, either hydrogen or additional bond at C-9 and C-11 and a substituent at both the C-6 and Cl6 positions. As indicated herein, the substituent at the 6-position is fluorine in the tar-configuration. We consider chloro and methyl to be the equivalents of fluoro at the 6-position insofar as the unique and advantageous properties are concerned.
The anti-allergy effects were first determined in mice by standard pharmacological evaluation. In this test,
0 the test animal is sensitized with horse serum and serum challenge generally results in death to untreated animals. The steroids being tested are administered intramuscularly eighteen hours prior to the anaphylactic challenge. Observations are then made on the degree of protection afforded in groups of animals, each group receiving varying dosages of different compounds. Only those compounds which provided significant protection at a dose of about 50 mg./kg. were considered of value. The test compounds then were submitted to the standard adrenocorticoid evaluation, such as the granulona pouch test, thymus involution test, depression of circulating eosinphiles test and the like and the dose required to elicit a positive response in these tests was compared with the dose required to elicit the aforedescribed antiallergy (or anti-anaphylactic effect). The selected steroids claimed herein in the form of pharmaceutical formulations uniquely exhibited a separation of properties resulting in an unobvious and extremely valuable therapeutic ratio of anti-allergic dose to adrenocorticoid dose.
The effective dosage of the steroid compounds described herein depends upon the severity, the stage and the individual characteristics of each case and will be determined by an attending veterinarian or physician. Generally a dosage range of from about 0.1 to about 3.0 mg. per kg. of body weight per day constitutes the overall range. The steroids described herein are preferably administered orally in the form of tablets, capsules, elixers, solutions, sprays and the like. A particularly advantageous form for utilization in asthmatic conditions is as an aerosol spray taken directly into the mouth so that direct and intimate contact with lung tissue is achieved. Spray formulations may be conveniently administered nasally. Other modes of administration are via the topical and opthalmic route utilizing appropriate dosage forms such as solutions, ointments, and the like. In certain situations parenteral administration, either intramuscular or intravenous, may be called for such as extemporaneous treatment of anaphylactic shock. Dosage forms adaptable for such administration are sterile solutions and suspensions of the particular steroids. Of particular adaptability for such dosage formulations are soluble esters of the unique steroids described herein. Said esters are represented by the 21-phosphates in the form of monoor di-sodium salts, or the sodium salt of a 21-hemisuccinate. These salts and in particular the latter, are conveniently prepared in situ in the presence of a buffering agent which will establish a pH between about 6.5 and about 8.0. A preferred method for preparing such an ester is to prepare an aqueous solution of the 21-hemisuccinate in aqueous alkali in the presence of sodium dihydrogen phosphate and lyophilizing after sterilization by special filtration according to the method described in US. Patent No. 3,193,459. There is thus obtained a sterile water-soluble powder consisting of the sodium salt of the 21-hemisuccinate of, in the case of the preferred species, 6a-fluoro-16rx-methyl-1,4,9(11)- pregnatriene-17a,21-diol-3,20-dione. The pharmaceutical formulations generally described above may also include other therapeutic agents such as adrenocortical steroids, antihistamines, antibiotics, and the like, the composition of which will be regulated by the condition being treated.
The following formulations are exemplary of pharmaceutical compositions representing the tangible embodi ments of our invention. The means by which the various formulations are actually compounded will be readily apparent to one skilled in the art.
EXAMPLE 1 Tablets Mg./ tab. 6a-fiuoro-16a-methyl-1,4,9 (11)-pregnatriene-17a,
21-diol-3,20-dione-21-acetate 5.00 Lactose 83.85
Starch 9.50
Gelatin 1. 19 Magnesium stearate 0.46
4 EXAMPLE 2 Tablets Mg./tab.
6a fluoro 16a methyl-1,4-pregnadiene-17ot,21-
diol-3,20dione-2l-acetate 10.0 Acetophenetidin 162.0 Caffeine, anhydrous 32.0 Acetylalicylic acid 227.67 Gelatin 5.0
Corn starch 55.33 Stearic acid 3.0
i The foregoing examples provide tablets for oral use 1n the treatment of allergic conditions. The quantity of steroid may be increased to about 30 mg. per tablet.
EXAMPLE 3 Aqueous suspension Mg./ml. 60c fluoro-16ot-methyl-1,4,9(1l)-pregnatriene-17ct,
21-diol-3,20-dione' 5.0 Potassium dihydrogen phosphate, 0.? 6.0 Disodium hydrogen phosphate, OP. anhydrous z 12.0
Polysorbate 80, U.S.P 0.4 Sorbitan monolaurate (Span 20-Atlas) 0.4 Thimerosal,N.F 0.1 Water for injection, U.S.P., to make 1.0 ml.
EXAMPLE 4 Nasal spray Mg./ml. 60 fluoro-l6wmethyl-l,4-pregnadiene-l7a,21-diol- 3,20-dione-21-acetate 10.0 Chlorpheniramine gluconate 3.0 D-sorbitol 43.0 Benzalkonium chloride, U.S.P. 0.25 Distilled water, to make 1.0 ml.
EXAMPLE 5 Injectable oil suspension Mg/ml. 60c fiuoro-l6a-methyl-l,4,9(l l )-pregnatriene-l7a,
2l-diol-3,20-dione-2l-acetate 5.0
Aluminum monostearate 20.0
Trichloromonofluoromethane, 14.0 microliters. Dichlorodifluoromethane: Dichlorotetrafiuoroethane (50:
50), q.s. to 50 microliters.
The foregoing formation is administered through a metered valve designed to deliver 50 microliters per spray.
5 EXAMPLE 8 Lyophilized powder for intravenous injection of aqueous solution Mg./m1. of reconstituted solution 6m fiuoro16a-methyl-1,4,9( l 1)-pregnatriene-1'7a,
21-dio1-2,20-dione-2l-hemisuccinate sodium salt- 69.4 Sodium dihydrogen phosphate 8.75 Disodium hydrogen phosphate, anhydrous 10.35
EXAMPLE 9 Ophthalmic solution Mg./ml. 6oz fluoro 16cc methyl-1,4 pregnadiene-17a,2l-
diol-3,20-dione-2lphosphate 6.52 Sodium dihydrogen phosphate 1.0 Sodium chloride 8.0 Merthiolate 0.1 Benzyl alcohol 5.0 Chloro butanol 5.0
Water, q.s. 1.0 ml.
In the above formulations the active ingredients have been indicated to be 6u-fiuoro-l6a-methyl-l,4,9(l1)- pregnatriene-l7ec,2l-diol-3,20dione or the corresponding 9,11-dihydro analogs either in the form of their free 21-01 or as certain selected esters thereof. It is to be understood that these examples have been presented for the purpose of lilustration only and that the other steroids and the equivalents thereof mentioned herein as possessing the unique separation of properties described heretofore may be used equally. It is to be understood that in the various pharmaceutical compositions, the concentration of the 0 active ingredient will be such that an amount of com position which can be conveniently administered during each treatment will contain a suflicient quantity of such active ingredient which Will elicit an appropriate and proper therapeutic response.
We claim:
1. A method of eliciting an anti-allergic effect in mammals which comprises administering to a mammal having an allergic disorder a therapeutically effective quantity of a compound selected from the group consisting of 60afluoro 16 methyl 1,4,9(11) pregnatriene 17,21- diol 3,20 dione, 6a fluoro 16 methyl 1,4 pregnadiene-17a,21-diol-3,20-dione and the C-21-pharm-aceutically acceptable esters thereof.
2. The method of claim 1 wherein the compound is administered in a composition suitable for oral administration.
3. The method of claim 1 wherein the compound is administered in the form of a bronchial spray.
4. The method of claim 1 wherein the compound is administered in a daily dose range of from about 0.1 to about 3.0 mg. per kg. of body weight.
5. The method of claim 1 wherein there is administered a therapeutically effective quantity of 6u-fluoro-l6amethyl 1,4,9(l1) preguatriene 1704,21 diol 3,20- dione.
6. The method of claim 1 wherein there is administered a therapeutically efiective quantity of a C-21-pharma ceutically acceptable ester of (Sat-fluoro-16ot-methyl-l,4,9 (11)-pregnatriene-17a,2 l-diol-3,20-dione.
References Cited UNITED STATES PATENTS 3,192,201 6/1965 Westerhof 260-239.5 3,198,792 8/1965 Reerink et al. 260-23955 FOREIGN PATENTS 933,859 8/1963 Great Britain.
RICHARD L. HUFF, Primary Examiner
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US52067566A | 1966-01-14 | 1966-01-14 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| US3463852A true US3463852A (en) | 1969-08-26 |
Family
ID=24073614
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US520675A Expired - Lifetime US3463852A (en) | 1966-01-14 | 1966-01-14 | Treating allergies with steroids of the pregnane series |
Country Status (4)
| Country | Link |
|---|---|
| US (1) | US3463852A (en) |
| FR (1) | FR6111M (en) |
| GB (1) | GB1115893A (en) |
| NL (1) | NL6700544A (en) |
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4051241A (en) * | 1975-03-10 | 1977-09-27 | Syntex (U.S.A.) Inc. | Method of treating diseases by daily administration of 6-chloro-11β,17α,21-trihydroxypregna-1,4,6-triene-3,20-dione |
| US4358445A (en) * | 1979-11-16 | 1982-11-09 | Macdonald Peter | 6α-Fluoro-prednisdone 17,21 diesters |
| US4902681A (en) * | 1987-08-27 | 1990-02-20 | University Of Pennsylvania | Inhibition of immune clearance using progesterone analogues |
| US4908358A (en) * | 1987-08-27 | 1990-03-13 | Trustees Of The University Of Pennsylvania | Inhibition of immune clearance using progesterone analogues |
| US6001367A (en) * | 1997-01-03 | 1999-12-14 | L'oreal | Cosmetic and/or dermatological composition containing a dispersion of a polymeric system and use of this system as tensor |
| US20070292468A1 (en) * | 2006-06-14 | 2007-12-20 | Joel Studin | Coated jewelry articles to reduce skin irritation |
| US20100087408A1 (en) * | 2008-05-28 | 2010-04-08 | Validus Genetics | NON-HORMONAL STEROID MODULATORS OF NF-kB FOR TREATMENT OF DISEASE |
| US9198921B2 (en) | 2010-04-05 | 2015-12-01 | Reveragen Biopharma, Inc. | Non-hormonal steroid modulators of NF-κB for treatment of disease |
| US10799514B2 (en) | 2015-06-29 | 2020-10-13 | Reveragen Biopharma, Inc. | Non-hormonal steroid modulators of NF-kappa beta for treatment of disease |
| US11382922B2 (en) | 2019-03-07 | 2022-07-12 | Reveragen Biopharma, Inc. | Aqueous oral pharmaceutical suspension compositions |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA1310009C (en) * | 1984-03-28 | 1992-11-10 | John Mark Braughler | Ester prodrugs of steroids |
| GB2396815B (en) * | 1999-10-27 | 2004-09-08 | Phytopharm Plc | A composition comprising a pregnenone derivative and an NSAID |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB933859A (en) * | 1958-09-06 | 1963-08-14 | Syntex S.A. | |
| US3192201A (en) * | 1958-04-12 | 1965-06-29 | Philips Corp | Steroid enamines |
| US3198792A (en) * | 1962-06-12 | 1965-08-03 | Philips Corp | 10alpha methyl, 9beta hormonal steroids |
-
1966
- 1966-01-14 US US520675A patent/US3463852A/en not_active Expired - Lifetime
-
1967
- 1967-01-12 GB GB1681/67A patent/GB1115893A/en not_active Expired
- 1967-01-13 NL NL6700544A patent/NL6700544A/xx unknown
- 1967-01-13 FR FR91020A patent/FR6111M/fr not_active Expired
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3192201A (en) * | 1958-04-12 | 1965-06-29 | Philips Corp | Steroid enamines |
| GB933859A (en) * | 1958-09-06 | 1963-08-14 | Syntex S.A. | |
| US3198792A (en) * | 1962-06-12 | 1965-08-03 | Philips Corp | 10alpha methyl, 9beta hormonal steroids |
Cited By (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4051241A (en) * | 1975-03-10 | 1977-09-27 | Syntex (U.S.A.) Inc. | Method of treating diseases by daily administration of 6-chloro-11β,17α,21-trihydroxypregna-1,4,6-triene-3,20-dione |
| US4358445A (en) * | 1979-11-16 | 1982-11-09 | Macdonald Peter | 6α-Fluoro-prednisdone 17,21 diesters |
| US4902681A (en) * | 1987-08-27 | 1990-02-20 | University Of Pennsylvania | Inhibition of immune clearance using progesterone analogues |
| US4908358A (en) * | 1987-08-27 | 1990-03-13 | Trustees Of The University Of Pennsylvania | Inhibition of immune clearance using progesterone analogues |
| US6001367A (en) * | 1997-01-03 | 1999-12-14 | L'oreal | Cosmetic and/or dermatological composition containing a dispersion of a polymeric system and use of this system as tensor |
| US20070292468A1 (en) * | 2006-06-14 | 2007-12-20 | Joel Studin | Coated jewelry articles to reduce skin irritation |
| US20100087408A1 (en) * | 2008-05-28 | 2010-04-08 | Validus Genetics | NON-HORMONAL STEROID MODULATORS OF NF-kB FOR TREATMENT OF DISEASE |
| US8207151B2 (en) | 2008-05-28 | 2012-06-26 | Validus Biopharma Inc. | Non-hormonal steroid modulators of NF-κB for treatment of disease |
| US8334279B2 (en) | 2008-05-28 | 2012-12-18 | Validus Genetics | Non-hormonal steroid modulators of NF-κB for treatment of disease |
| US8673887B2 (en) | 2008-05-28 | 2014-03-18 | Reveragen Biopharma, Inc | Non-hormonal steroid modulators of NF-kB for treatment of disease |
| US10857161B2 (en) | 2008-05-28 | 2020-12-08 | Reveragen Biopharma, Inc. | Non-hormonal steroid modulators of NF-kB for treatment of disease |
| US9434758B2 (en) | 2008-05-28 | 2016-09-06 | Reveragen Biopharma, Inc. | Non-hormonal steroid modulators of NF-κB for treatment of disease |
| US9649320B2 (en) | 2008-05-28 | 2017-05-16 | Reveragen Biopharma, Inc. | Non-hormonal steroid modulators of NF-κB for treatment of disease |
| US11833159B2 (en) | 2008-05-28 | 2023-12-05 | Reveragen Biopharma, Inc. | Non-hormonal steroid modulators of NF-kB for treatment of disease |
| US10206933B2 (en) | 2008-05-28 | 2019-02-19 | Reveragen Biopharma, Inc. | Non-hormonal steroid modulators of NF-kB for treatment of disease |
| US9198921B2 (en) | 2010-04-05 | 2015-12-01 | Reveragen Biopharma, Inc. | Non-hormonal steroid modulators of NF-κB for treatment of disease |
| US10000525B2 (en) | 2010-04-05 | 2018-06-19 | Reveragen Biopharma, Inc. | Non-hormonal steroid modulators of NF-κB for treatment of disease |
| US10799514B2 (en) | 2015-06-29 | 2020-10-13 | Reveragen Biopharma, Inc. | Non-hormonal steroid modulators of NF-kappa beta for treatment of disease |
| US11690853B2 (en) | 2015-06-29 | 2023-07-04 | Reveragen Biopharma, Inc. | Non-hormonal steroid modulators of NF-κβ for treatment of disease |
| US11382922B2 (en) | 2019-03-07 | 2022-07-12 | Reveragen Biopharma, Inc. | Aqueous oral pharmaceutical suspension compositions |
| US11471471B2 (en) | 2019-03-07 | 2022-10-18 | Reveragen Biopharma, Inc. | Aqueous oral pharmaceutical suspension compositions |
Also Published As
| Publication number | Publication date |
|---|---|
| GB1115893A (en) | 1968-05-29 |
| FR6111M (en) | 1968-06-17 |
| NL6700544A (en) | 1967-07-17 |
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