• 专利附录
  • 专利说明
  • 权利要求
  • 类似技术
  • 同族专利
  • 引用文献
  • 法律状态
  • 优先权
    • 专利摘要:
    The present invention provides a pharmaceutical formulation in the form of a capsule for oral administration comprising testosterone undecanoate, the active ingredient dissolved in a pharmaceutically acceptable liquid carrier, wherein the liquid carrier comprises at least 50% by weight castor oil. It relates to a pharmaceutical formulation. If castor oil is selected as the liquid carrier and testosterone undecanoate is selected as the androgen, the solution may comprise between 200 and 250 mg of TU per ml. This is a new achievement for any form of testosterone solution for any oral administration. The solution also contains a lipophilic surfactant such as lauroglycol.
    公开号:KR20010108435A
    申请号:KR1020017012498
    申请日:2000-03-27
    公开日:2001-12-07
    发明作者:니즈스데헨릭；챈들러수잔；페리엘리자베스앤；페르디난도조세핀존크리스틴
    申请人:에프.지.엠. 헤르만스 ; 이.에이치. 리링크；악조 노벨 엔.브이.；
    IPC主号:
    专利说明:

    Formulation containing testosterone undecanoate and castor oil {FORMULATION COMPRISING TESTOSTERON UNDECANOATE AND CASTOR OIL}
    [2] Such formulations are attracting new attention in terms of developing formulations for male contraception and male HRT (hormone replacement therapy). In both cases, androgens can be used in particular as substitutes for endogenous testosterone. That is, for example, in male HRT, androgens are administered androgens to alleviate the undesirable effects of (partial) androgen deficiency that may appear with age. Androgens can also be used in women, for example as androgen replacement therapy in postmenopausal women.
    [3] Androgen oral preparations are rare, and the only oral natural testosterone product on the market is a solution of testosterone undecanoate (TU) in oleic acid. This product is known in various countries under various brand names, for example, Andriol (registered trademark) or Restandol (registered trademark), which is a soft gelatin capsule formulation containing 40 mg of TU dissolved in oleic acid. In order to reach and maintain an acceptable testosterone blood level, the capsules should be administered three to four times daily. Such multiple dose regimens are not well suited for the actual use of TUs as acceptable HRT products, but in such a way they can be contraceptive.
    [4] The present invention is to solve the problem of providing an orally active androgen preparation that is well absorbed in the human body. Specifically, the present invention is to provide a TU formulation having a higher strength than the known TU formulation described above.
    [1] The present invention relates to the field of androgen preparations for oral administration.
    [5] In accordance with the above and other objects, the present invention provides a pharmaceutical formulation in the form of a capsule for oral administration comprising the active ingredient testosterone undecanoate dissolved in a pharmaceutically acceptable liquid carrier, wherein the liquid carrier is castor oil. do. In one embodiment, only castor oil may be used as the liquid carrier, but castor oil and other liquid carriers may be combined. However, it is preferable that castor oil constitutes the main component of the liquid carrier, that is, constitute 50% by weight or more of the carrier.
    [6] If castor oil is selected as the liquid carrier and testosterone undecanoate is selected as the androgen, the solution may comprise between 200 and 250 mg of TU per ml. This is the equivalent of about 127-137 mg of testosterone per ml. This is a new achievement for any form of testosterone solution for any oral administration. Thus, one aspect of the present invention includes a pharmaceutical formulation in the form of a capsule for oral administration comprising the active ingredient testosterone undecanoate dissolved in a concentration of 200 to 250 mg / ml in a pharmaceutically acceptable liquid carrier.
    [7] Exp. Clin. Endocrinol. Diabetis 105 Suppl. 1, 21, 1997 and Eur. J. Endocrinol. 123: 514-9 (195) describe injectables containing 250 mg / ml TU in castor oil. However, it never suggests a way to orally administer similar concentrations of TUs. It is a separate field of pharmaceutical preparations and moreover, direct injection into the muscle cannot be used as an oral route of administration. Furthermore, it is even more surprising that castor oil is suitable as a carrier for administration of this type, especially because of its normal performance as a laxative. Of course, it is a completely opposite use of the present invention, and the purpose is to introduce and absorb an object (in this case, a TU) into the body rather than to induce it to be released out of the body. That is, it is not unexpected that castor oil is a very suitable carrier for oral administration of TU that is well absorbed.
    [8] The invention also relates to the use of testosterone undecanoate in the preparation of a drug in the form of an oral solution in which testosterone undecanoate is dissolved in a pharmaceutically acceptable liquid carrier, wherein the liquid carrier is at least 50% by weight castor oil. Characterized in that it comprises a. The present invention also relates to a method of treatment comprising administering testosterone undecanoate to a man or woman in need of androgen supplementation, wherein the testosterone undecanoate is administered orally in the form of a solution in a carrier, wherein the carrier is 50 weight It is characterized by containing more than% castor oil. In order to realize optimal TU administration, capsules are preferably taken during or immediately after a meal.
    [9] In aspects of the invention as described above, in addition to TU and castor oil, the capsule preferably comprises additives as disclosed in WO 97/40823 and WO 95/24893. It is preferred that the formulation is based on a specific combination of castor oil and a lipophilic surfactant, since such formulations provide a liquid excipient that dissolves TU to form the most stable formulation that most facilitates lymphatic vessel absorption. That is, preferred formulations have a TU value in a liquid excipient comprising 50-70% by weight castor oil, 30-50% by weight lipophilic surfactant (HLB <10) and optionally 0-20% by weight hydrophilic surfactant. Is dissolved and the liquid excipient is substantially free of free fatty acids and contains less than 10% by weight of ethanol. Suitable as lipophilic surfactants with HLB <10 are well known to those skilled in the art. Such surfactants include monoglycerides and / or diglycerides of fatty acids, as well as fatty acids to which the remaining free OH groups of glycerol can be esterified, for example their acetic acid esters, succinic esters, lactic acid esters, citric acid esters and / or tartaric acid. Monoglycerides and / or diglycerides of esters; Propylene glycol monoesters and / or diesters of fatty acids; Ethoxylates of castor oil or hydrogenated castor oil (low ethoxylate content, HLB <10); Acids and ester ethoxylates formed by reacting ethylene oxide with glycerol esters of fatty acids or fatty acids; Sorbitan esters of fatty acids; Unsaturated polyglycolated glycerides (if HLB <10); Alcohol ethoxylates (if HLB <10); Polyoxyethylene-polyoxypropylene copolymers and block copolymers (when HLB <10). The lipophilic surfactant is preferably used in an amount ranging from 35 to 45% by weight of the liquid excipient. Preferred lipophilic surfactants are lauroglycol (propylene glycol monolaurate). Any hydrophilic surfactant is also well known to those skilled in the art. Any pharmaceutically acceptable hydrophilic surfactant (ie, having an HLB value of 10 or more) can be used in the present invention. The formulations of the present invention may contain trace amounts of other additives such as antioxidants such as d-α-tocopherol, BHA, BHT; Cosolvents such as ethanol and transcutol (diethylene glycol monoethyl ether); Plasticizers such as propylene glycol and the like.
    [10] The formulations of the present invention can be readily prepared by known methods, for example as disclosed in WO 95/24893. Capsules encapsulating the formulations of the invention can be prepared by known techniques. Gelatin soft gels such as Andriol® are preferred, but any soft shell or hard shell material may be used as long as the walls of the capsule are pharmaceutically acceptable. Soft gel encapsulation method is described in the literature [Theory and Practice of Industrial Pharmacy- Lachman & Liebermann, 2 nd Edition, published by Henry Kimpton Publishers, London]. Liquid filled hard shell encapsulation methods are disclosed in Hardcapsules-Development and Technology-Edited by K. Ridgeway, published by Pharmaceutical Press 1987.
    [11] Next, the present invention will be described in more detail with reference to Examples.
    [12] Example
    [13] The following ingredients were added to a suitable mixer (Unimix) and heated to 40 ° C.
    [14] Castor oil BP 53 parts by weight
    [15] Lauroglycol FCC 35 parts by weight
    [16] Testosterone Undecanoate 12 parts by weight
    [17] After complete dissolution, the resulting solution was filled into 330 ml of soft gelatin capsules using a standard apparatus. This gave a stable formulation that absorbed TU well orally.
    权利要求:
    Claims (8)
    [1" claim-type="Currently amended] A pharmaceutical formulation in the form of a capsule for oral administration comprising testosterone undecanoate, the active ingredient dissolved in a pharmaceutically acceptable liquid carrier, wherein the liquid carrier comprises at least 50% by weight castor oil. .
    [2" claim-type="Currently amended] The pharmaceutical formulation of claim 1 wherein the single liquid carrier is castor oil.
    [3" claim-type="Currently amended] The pharmaceutical formulation of claim 1, wherein the liquid carrier further comprises 30-50% by weight of a lipophilic surfactant having an HLB value of 10 or less.
    [4" claim-type="Currently amended] The pharmaceutical formulation of claim 3 wherein the lipophilic surfactant is lauroglycol.
    [5" claim-type="Currently amended] The pharmaceutical formulation according to any one of claims 1 to 4, wherein testosterone undecanoate is dissolved at a concentration of 200 to 250 mg / ml.
    [6" claim-type="Currently amended] Use of testosterone undecanoate for the manufacture of a drug in oral solvent form in which testosterone undecanoate is dissolved in a pharmaceutically acceptable liquid carrier, wherein the liquid carrier comprises at least 50% by weight castor oil. .
    [7" claim-type="Currently amended] A method of treatment comprising administering testosterone undecanoate to a man in need of androgen supplementation, wherein the testosterone undecanoate is administered orally in the form of a solution in a carrier, wherein the carrier comprises at least 50% by weight castor oil. How to feature.
    [8" claim-type="Currently amended] A pharmaceutical formulation in the form of a capsule for oral administration comprising the active ingredient testosterone undecanoate dissolved in a concentration of 200 to 250 mg / ml in a pharmaceutically acceptable liquid carrier.
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    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    法律状态:
    1999-04-01|Priority to EP99302581
    1999-04-01|Priority to EP99302581.6
    2000-03-27|Application filed by 에프.지.엠. 헤르만스 ; 이.에이치. 리링크, 악조 노벨 엔.브이.
    2001-12-07|Publication of KR20010108435A
    2007-01-10|Application granted
    2007-01-10|Publication of KR100666016B1
    优先权:
    申请号 | 申请日 | 专利标题
    EP99302581|1999-04-01|
    EP99302581.6|1999-04-01|
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