Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/20—Pills, tablets, discs, rods
  • A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
  • A61K9/2806—Coating materials
  • A61K9/2833—Organic macromolecular compounds
  • A61K9/286—Polysaccharides, e.g. gums; Cyclodextrin
  • A61K9/2866—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose

Definitions

• BACKGROUND OF THE INVENTION Disturbances of the normal hormonal equilibrium in warm-blooded mammals is manifested by various diseases and disturbances of varying degrees of severity. For example, in the climacteric, including the preand postclimacteric periods, the symptoms and/ or the corresponding pathological deficiencies Which occur are attributable to a disturbance of the hormonal equilibrium. Decreasing vitality With increasing age is likewise attributable to a disturbance in the normal hormonal equilibrium. Some dematological manifestations are also hormone-dependent, for example, hirsutism seems to be caused by a hormonal imbalance.
• sulphoconjugated neutral steroids mean non-phenolic steroids Which are esterified with sulphuric acid or with sulphuric acid derivatives, i.e., the sulphates or sulphatides of the steroids.
• non-phenolic steroids are, for example, cholesterol, C -steroids such as pregnenolone, desoxycorticosterone, progesterone (in enol form), C -steroids such as dehydro-epi-androsterone, testosterone, C -steroids such as 19-nortestosterone.
• Particularly preferred compounds useful in the practice of this invention are pregnenolone and dehydro-epi-androsterone in the form of the sulphate or sulphatide.
• Sulphates as used herein include both the acidic sulphates and the mixed salts of sulphuric acid with a nontoxic pharmaceutically acceptable cation such as, for example, ammonium, sodium, potassium and calcium.
• a nontoxic pharmaceutically acceptable cation such as, for example, ammonium, sodium, potassium and calcium.
• the alcoholic part of the ester must be derived from a non-toxic pharmaceutically acceptable monovalent or polyvalent alcohol, e.g., from glycerine or higher fatty alcohols such as palmityl or stearyl alcohol.
• composition of this invention in unit dosage form is controlled by the particular needs of the patients and by the symptoms and disease being treated as Well as by the specific active substance being used.
• a dosage of between about mg. and about 30 mg. of dehydro-epi-androsterone 3- sulphate per day has proven efficacious for influencing menopausal symptoms as it is evident from Table I and II:
• gastric-juice-resistant composition is conventional.
• polyelectrolytes containing carboxyl groups are used.
• natural lacquers such as keratin, shellac, collophony
• cellulose esters containing carboxyl groups such as acetyl-phthalyl-cellulose, acetyl-succinyl-cellulose
• copolymers containing carboxyl groups which contain maleic acid as the acid component such as copolymers of styrene and maleic acid anhydride, copolymers of butyl partial ester of maleic acid with styrene and small amounts of acrylic acid, copolymers of maleic acid anhydride and vinyl methyl ether
• copolymers containing carboxyl groups which contain acrylic acid or methacrylic acid as the acid component such as copolymers of styrene and methacrylic acid.
• the manufacture of the unit dosage form used in this invention is achieved by conventional methods using conventional equipment.
• the film-forming material which is resistant to gastric juice is brought into solution by means of a solvent.
• Any medicinally acceptable solvent in which the film-forming material is soluble can be used for the manufacture of the solution.
• cellulose acetate phthalate is used as the gastricjuice-resistant coating material
• methylene chloride usually mixed with a small amount of a lower alkanol, is advantageously used as the solvent.
• the concentration of the solution used can vary within wide limits. However, it is convenient that the solution contain about 7 to 12 parts by weight of solvent per part by weight of coating material.
• the coating procedure is conventional.
• the nucleus, in tablet form, containing the sulpho-conjugated neutral steroid is treated with the solution containing the coating material in a coating drum. By rotation of the coating drum, a thin uniform coating is produced on the tablets.
• the coated tablets are subsequently dried and this coating-drying process repeated several times until a sufiicient layer of the gastric-juice-resistant coating is present on the tablets to ensure that the tablets will be unaffected by gastric-sjuice.
• the invention is illustrated by the following example.
• Dragee nuclei of 75 mg. weight and a diameter of 6 mm. containing 10.0 mg. of sodium dehydro-epi-androsterone sulphate, 50.00 mg. of lactose, 13.50 mg. of corn starch, 1.35 mg. of talc and 0.15 mg. of magnesium stearate per nucleus are formed and coated with a gastricjuice-resistant lacquer layer by using a lacquer solution consisting of parts by weight of cellulose acetate phthalate, 3 parts by weight of triacetin, 10 parts by weight of ethanol and 77 parts by weight of methylene chloride. A suflic'ient resistance to gastric juices is ensured by application of about 25 layers.
• the coating amounts to about 10 mg. per nucleus.
• the lacquered nuclei obtained are dried at about 37 C. for 24-36 hours and then dredged until they have an end weight of about mg.
• composition according to claim 1 wherein said steroid compound is dehydro-epi-androsterone in the form of sulphate.
• composition according to claim 1 wherein said steroid compound is pregnenolone in the form of a sulphate.
• composition according to claim 1 wherein said steroid compound is pregnenolone in the form of a sulphatide.
• a sulpho-conjugated neutral steroid compound selected from the group consisting of the sulphates and sulphatides of dehydro-epi-androsterone and pregnenolone, the improvement which comprises administering said steroid in the form of a tablet nucleus which is coated with a gastric-juice-resistant layer of polyelectrolytes containing carboxyl groups.
• said steroid compound is selected from the group consisting of dehydro-epi-androsterone, the sulphate thereof and the sulphatide thereof.
• said steroid compound is selected from the group consisting of pregnenolone, the sulphate thereof and the sulphatide thereof.

Landscapes

• Health & Medical Sciences (AREA)
• Epidemiology (AREA)
• Bioinformatics & Cheminformatics (AREA)
• Chemical & Material Sciences (AREA)
• Medicinal Chemistry (AREA)
• Pharmacology & Pharmacy (AREA)
• Engineering & Computer Science (AREA)
• Life Sciences & Earth Sciences (AREA)
• Animal Behavior & Ethology (AREA)
• General Health & Medical Sciences (AREA)
• Public Health (AREA)
• Veterinary Medicine (AREA)
• Medicinal Preparation (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Applications Claiming Priority (1)

Publications (1)

Family

ID=4366476

Family Applications (1)

Country Status (6)

Cited By (2)

Families Citing this family (1)

• 1968
  • 1968-06-28 DE DE19681767898 patent/DE1767898A1/de active Pending
  • 1968-07-08 NL NL6809629A patent/NL6809629A/xx unknown
  • 1968-07-15 US US744675A patent/US3600495A/en not_active Expired - Lifetime
  • 1968-07-18 GB GB34358/68A patent/GB1188629A/en not_active Expired
  • 1968-07-25 BE BE718543D patent/BE718543A/xx unknown
  • 1968-07-29 FR FR160942A patent/FR8158M/fr not_active Expired

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