Composition comprising testosterone undecanoate and castor oil
FIELD: medicine, pharmacy.
SUBSTANCE: invention relates to a pharmaceutical composition as a capsule for oral administration that comprises testosterone undecanoate as an active component dissolved in pharmaceutically acceptable liquid carrier wherein liquid carrier involves at least 50 wt.-% of castor oil. Using castor oil as a liquid carrier in combination with testosterone undecanoate as androgen provides preparing a solution that can contain about 200-250 mg of testosterone undecanoate/ml that represents the new achievement for testosterone solution for oral administration. Solution can contain lipophilic surface-active substance, such as lauryl glycol also. The composition shows good absorption in human body and elicits higher activity as compared with the known composition of undecanoate.
EFFECT: improved and valuable properties of composition.
7 cl, 1 ex
The present invention relates to the field of compositions for oral androgen administration. Such compositions once again aroused the attention in connection with the development of drugs for male contraception and GST men (hormone replacement therapy). In both cases, androgen may, in particular, be used as a replacement of endogenous testosterone. Thus, for example, in male GST androgen is administered to alleviate the undesirable effects (partial) androgen deficiency, which can be a consequence of age. Androgens can also be used for the treatment of women, such as androgen replacement therapy postmenopausal women.
Oral preparations of androgens are rare, the only commercially available oral natural-product of testosterone is a solution of testosterone undecanoate (UT) in oleic acid. This product, which is known in various countries under various brand names, such as Andriol® or Restandol®represents the preparative form soft gelatin capsule containing 40 mg UT dissolved in oleic acid. To achieve and maintain acceptable levels of testosterone in the blood daily should take 3-4 such capsules. Mode that includes such a huge number of individual techniques of preparation is the same not very convenient for practical use UT as a suitable product for GST, not to mention the acceptability of this method of contraception.
The objective of the invention is to solve the problem of providing orally active composition of androgen, which is well absorbed in the human body. In particular the invention aims to develop compositions UT, which has higher activity than known UT composition, referred to above.
To meet these and other objectives, the invention provides a pharmaceutical composition in the form of capsules for oral administration, comprising undecanoate testosterone as the active ingredient, dissolved in a pharmaceutically acceptable liquid carrier, where the carrier liquid is castor oil. Although in one embodiment of the invention castor oil may be the only liquid media can also combine castor oil with other liquid media. However, it is desirable that castor oil was the main component of a liquid medium, i.e. accounted for more than 50% of the mass. the specified media.
The choice of castor oil as a liquid carrier, in combination with the choice of testosterone undecanoate as the androgen, giving a solution which may contain approximately 200-250 mg UT on Jr. Is with what constitutes from about 127 to 137 mg of testosterone per ml, what is a new achievement for any oral injectate testosterone in any form. Therefore, the invention in one aspect includes a pharmaceutical formulation in the form of capsules for oral administration containing undecanoate testosterone as the active ingredient, dissolved in a pharmaceutically acceptable liquid medium with a concentration of 200-250 mg/ml
It is noted that Exp. Clin. Endocrinol. Diabetis 105 Suppl.1,21,1997 and Eur. J. Endocrinol. 132:514-9 (195) mentions a solution for injection to a concentration of 250 mg/ml UT in castor oil. However, this does not shows the possibility of achieving similar levels of UT when administered orally. This is a separate pharmaceutical formulations and, moreover, injection directly into the muscle cannot be used as a model for the introduction of the oral method. In addition, more amazing is that castor oil is a particularly suitable medium for this type of introduction, as his usual action is laxative effect. Of course, this property is completely opposite to the purposes of the present invention, which is to make something (in this case, UT) to enter and be absorbed in the human body, not to cause it to leave the body, causing extractio. Therefore, Ki is completely unexpected, that castor oil is very convenient carrier for oral administration UT, which is well absorbed.
The invention also includes the use of testosterone undecanoate for the manufacture of a medicinal product in the form for oral solution, where undecanoate testosterone dissolved in a pharmaceutically acceptable liquid carrier, which is characterized in that the liquid medium contains at least 50% by weight of castor oil. In another aspect, the invention is a method of treatment involving the introduction of testosterone undecanoate man or woman, if necessary, delivery of androgen, characterized in that undecanoate testosterone administered orally in the form of a solution in a carrier, the latter contains at least 50 wt%. castor oil. For optimum injection UT capsules should be taken preferably during or immediately after a meal.
In all the above aspects, it is preferable that in addition to UT and castor oil capsules include additives, such as described in WO 97/40823 and WO 95/24893. Most preferred is the use as the basis of composition, a specific combination of castor oil and lipophilic surfactants, because this combination provides a liquid races is varicel for dissolution UT, giving the most stable composition that best promote lymphatic absorption. Thus, the preferred composition is one in which UT is dissolved in a liquid solvent, which contains from 50 to 70% of the mass. castor oil and from 30 to 50 wt%. lipophilic surfactants with products HLB<10, and, optionally, from 0 to 20% of the mass. hydrophilic surfactants, where the liquid solvent is essentially no free fatty acids and it contains less than 10% of the mass. of ethanol. Suitable lipophilic surfactants with products HLB<10, known to specialists in this field. These compounds include mono - and/or diglycerides of fatty acids, and mono - and/or diglycerides of fatty acids, in which the remaining free Oh groups of the glycerol can be tarifitsirovana, obtaining esters of acetic, succinic, lactic, citric and/or tartaric acids; mono - and/or diesters of propylene glycol with fatty acids, ethoxylates of castor oil or hydrogenated castor oil (low ethoxylate, products HLB<10); acids and esters of ethoxylates obtained by the reaction of ethylene oxide with fatty acids or esters of glycerol with fatty acids; esters of sorbitol with fatty acids; unsaturated poliglecaprone glaze the IDA (if products HLB< 10); ethoxylates alcohols (if products HLB<10); copolymers and block copolymers of polyoxyethylene-polyoxypropylene (if products HLB<10). Lipophilic surfactant is preferably used in amounts in the range from 35 to 45% by weight of the liquid solvent. Preferred lipophilic surface-active agent is neuroglial (monolaurate propylene glycol). Optional hydrophilic surface-active substances are also known to specialists in this field. In the present invention can be any pharmaceutically acceptable hydrophilic surfactant (i.e. with products HLB value greater than 10). The composition can contain minor amounts of other additives, for example antioxidants, such as d-α-tocopherol, BHA, BHT; co-solvents such as ethanol and Transcutol (monotropy ether of diethylene glycol), plasticizers such as propylene glycol, etc.
The composition of the invention can be easily obtained with known methods, for example, described in WO 95/24893. Containing the composition of the capsules can be manufactured by known methods. Gelatin soft gels, as in the case of Andriol®are preferred, but the wall of the capsule may be made from any pharmaceutically acceptable material for soft or hard shell. Methods encapsulate with ISOE what Itanium soft gels described in theory and Practice of Industrial Pharmacy - Lachman & Leibermann, 2ndEdition, published by Henry Kimpton Publishers, London. Methods of encapsulation by liquid fill hard shell described in Hardcapsules - Development and Technology - published by K. Ridgeway, published by Pharmaceutical Press, 1987.
Further, the invention is additionally illustrated by the following example.
The following ingredients are added to a suitable mixing device (Unimix) and heated to 40°With:
Castor oil BP 53 parts by mass
Neuroglial FCC 35 parts by mass
Undecanoate testosterone 12 parts by mass
After complete dissolution, the resulting solution is filled 330 ál capsules soft gelatin using standard equipment. Get a stable composition from which UT is well absorbed orally.
1. Pharmaceutical composition in the form of capsules for oral administration, comprising undecanoate testosterone as the active ingredient, dissolved in a pharmaceutically acceptable liquid carrier, wherein the carrier liquid comprises at least 50 wt.% castor oil.
2. The pharmaceutical composition according to claim 1, characterized in that the sole carrier liquid is a castor oil.
3. The pharmaceutical composition according to claim 1, characterized in that the liquid medium additionally contains from 30 to 50 wt.% ipotechnogo surfactants, with products HLB value below 10.
4. The pharmaceutical composition according to claim 3, characterized in that the lipophilic surfactant is neuroglial.
5. The pharmaceutical composition according to any one of the preceding paragraphs, characterized in that undecanoate testosterone is dissolved with a concentration of 200-250 mg/ml
6. Method of preparation of a pharmaceutical composition for oral administration according to claim 1, including the dissolution of testosterone undecanoate in a pharmaceutically acceptable liquid carrier comprising at least 50 wt.% castor oil.
7. The method of treatment, including the introduction of testosterone undecanoate man if necessary, delivery of androgen, characterized in that undecanoate testosterone administered orally in the form of a solution in a carrier, the latter of which includes at least 50 wt.% castor oil.
FIELD: organic chemistry, steroids, pharmacy.
SUBSTANCE: invention describes unsaturated 14,15-cyclopropanoandrostanes of the general formula (I):
wherein R1 means hydrogen atom (H), hydroxy-group (OH); R2 means hydroxy-group (OH), hydrogen atom (H); R3 means hydrogen atom (H), (C1-C10)-alkyl at α- or β-position; R4 means halogen atom (F, Cl, Br) or pseudohalogen group (azide, rhodanide), hydroxy-group (OH), perfluoroalkyl; R5 means (C1-C4)-alkyl; if double bond is at 1,2-position then R4 can mean hydrogen atom (H). Also, invention relates to a method for preparing these compounds and pharmaceutical compositions containing these compounds. Compounds of the formula (I) are compounds eliciting gestagenic and/or androgenic effect.
EFFECT: improved preparing method, valuable medicinal properties of compounds.
11 cl, 1 tbl, 9 ex
where R1- Oh, (H,H), (H,OR), NOR, where R is H1-6alkyl, C1-6acyl; R2- H or C1-6alkyl, R3- H, or R3- C1-6alkyl, C2-6alkenyl,2-6quinil, possibly substituted with halogen, R4- H, C1-6alkyl or C2-6alkenyl; R5- C1-6alkyl, R5- H, R7- H, C1-6alkyl, R8Is H, OH, halogen;
R9and R10independently H, or R9and R10independently C1-6alkyl, possibly substituted C1-4alkoxy or halogen;
R11- H, SO3H1-15acyl, dashed line indicates a possible link from4,5(10)or4,9-diene system
FIELD: medicine, pharmacy.
SUBSTANCE: invention discloses compositions with sustained-release of active component and masking taste that comprise one of more active components included in tricomponent matrix structure as a globule. This structure is formed successively by amphiphilic, lipophilic or inert matrices and included as globule or dispersed in hydrophilic matrix. Applying large amount of systems for regulation of dissolving active component provides modulating the dissolving rate of active component in aqueous and/or biological fluids by regulating thus kinetics in releasing active component in digestive tract.
EFFECT: valuable pharmaceutical properties of compositions.
14 cl, 14 ex
FIELD: biotechnology, veterinary medicine.
SUBSTANCE: invention relates to the development of biological preparation for prophylaxis and treatment of colibacillosis (escherichiosis) and for control of carriage of escherichious infections pathogens in animals and poultries also. Also, invention can be used in producing curative fodders and ecologically pure human foodstuffs. Biopreparation for prophylaxis and treatment of escherichiosis in animals and poultries comprises strains of bacteriophages Phagum Escherichia coli Ec022-DEP and/or Phagum Escherichia coli Ec021-DEP, and/or Phagum Escherichia coli Ex0782-DEP, and/or Phagum Escherichia coli Ec0781-DEP, and/or Phagum Escherichia coli EPZ-1-DEP, and/or Phagum Escherichia coli EPZ-2-DEP, and/or Phagum Escherichia coli EG-5-DEP, and/or Phagum Escherichia coli BC-1-DEP, and/or Phagum Escherichia coli M78-DEP, and/or Phagum Escherichia coli Sheksna 2k-DEP taken in the effective amount. The biopreparation comprises also antiseptic, for example, quinosol and a stabilizing agent. Protein (for example, soybean protein), vegetable meal, organic polymer, milk, serum, albumin can be used as a stabilizing agent. Among organic polymers can be used: dextran, polyglucin, starch, polyvinylpyrrolidone. The biopreparation can be dried by lyophilization, granulated and placed in polymeric matrix. The biopreparation has no toxic properties on animals, it shows good hygroscopicity and can be good dispersed in water. The biopreparation can be used in liquid and dry prescription formulations and in different methods of its administrations: both by subcutaneous, intraperitoneal, intramuscular injections and as an aerosol, by administration of phage particles into lung compartments including applying as curative fodder and supplement to fodder, and by applying on surface of cutaneous integuments. Invention provides enhancing the effectiveness of treatment of animals and poultries with gastroenteric infections due to reducing treatment period, expanding spectrum of lytic effect of the biopreparation, resistance to effect of digestive tract enzymes and convenience in using.
EFFECT: valuable veterinary properties of biopreparation.
9 cl, 5 tbl, 7 ex