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KR-20260068090-A - Drug delivery system for the treatment of female sexual interest and arousal disorders

KR20260068090AKR 20260068090 AKR20260068090 AKR 20260068090AKR-20260068090-A

Abstract

The present invention relates to a dual-release drug delivery system for use in enhancing female sexual desire in the treatment of female sexual interest and arousal disorder (FSIAD). The composition comprises a core comprising a first active ingredient comprising cellulose, a filler selected from organic and/or inorganic salts, and a PDE 5 inhibitor for delayed immediate release; a first coating surrounding the core comprising a hydrophobic polymer and a hydrophilic material; and a second coating surrounding the first coating comprising a second active ingredient for immediate release, which is testosterone or a functional analog or derivative of testosterone. The delayed release of the first active ingredient is an immediate release occurring between 2 and 6 hours after the release of the second active ingredient; and the second active ingredient is present in an amount equivalent to 0.3 to 1.5 mg of testosterone, or an amount equivalent to 1.0 mg or more of testosterone. Additionally, the present invention relates to a method for enhancing female sexual desire in the treatment of female sexual interest and arousal disorder (FSIAD).

Inventors

  • 반 데르 무렌 마리우스 얀

Assignees

  • 알레타 파마 솔루션즈 홀딩 비.브이.

Dates

Publication Date
20260513
Application Date
20240905
Priority Date
20230905

Claims (20)

  1. As a dual-release drug delivery system for use in enhancing female sexual desire in the treatment of Female Sexual Interest and Arousal Disorder (FSIAD), the composition A core comprising cellulose, a filler selected from organic and/or inorganic salts, and a first active ingredient for delayed immediate release; A first coating surrounding the core and comprising a hydrophobic polymer and a hydrophilic material; and It comprises a second coating surrounding the first coating and containing a second active ingredient for immediate release; Here The first active ingredient comprises a PDE5 inhibitor; The second active ingredient is testosterone, or a functional analogue or derivative of testosterone, and The delayed release of the first active ingredient is an immediate release occurring between 2 and 6 hours, preferably between 2.5 and 3.5 hours, after the release of the second active ingredient; A dual-release drug delivery system in which the second active ingredient is present in an amount equivalent to 0.3 to 1.5 mg of testosterone.
  2. A dual-release drug delivery system according to claim 1, wherein the PDE5 inhibitor is selected from the group consisting of sildenafil, tadalafil, vardenafil, and combinations thereof, and, for example, the first active ingredient comprises sildenafil.
  3. A dual-release drug delivery system according to claim 1 or 2, wherein the first active ingredient is sildenafil and is present in an amount of 10 to 120 mg, preferably 20 to 100 mg, for example, 25 mg or 50 mg or 100 mg.
  4. A dual-release drug delivery system according to any one of claims 1 to 3, wherein the first active ingredient is administered orally and/or; and the second active ingredient is administered sublingually.
  5. A dual-release drug delivery system according to any one of claims 1 to 4, wherein the filler is an inorganic salt, e.g., anhydrous calcium phosphate and/or; and the cellulose is microcrystalline cellulose.
  6. A dual-release drug delivery system according to any one of claims 1 to 5, wherein the core further comprises a water-insoluble gel-forming disintegrant comprising cross-linked sodium carboxymethylcellulose, sodium starch glycolate, and/or cross-linked polyvinylpyrrolidone.
  7. A dual-release drug delivery system according to any one of claims 1 to 6, wherein the hydrophobic polymer is a hydrophobic polymer ethylcellulose and/or; the hydrophilic material is a water-insoluble hydrophilic material and the first coating contains pores before exposure to an aqueous liquid; or the hydrophilic material is a water-soluble hydrophilic material and the water-soluble hydrophilic material forms pores within the hydrophobic polymer upon exposure to an aqueous liquid.
  8. A dual-release drug delivery system according to any one of claims 1 to 7, wherein the second coating further comprises hydroxypropylmethylcellulose, and/or cyclodextrin or a derivative or polymer thereof.
  9. A dual-release drug delivery system according to any one of claims 1 to 8, wherein the second active ingredient is present in an amount corresponding to 0.4 to 1.5 mg, for example, 0.5 mg or 1.0 mg.
  10. A dual-release drug delivery system in which, in any one of claims 1 to 9, the drug delivery system is a tablet.
  11. A method for enhancing a woman's sexual desire in the treatment of female sexual interest and arousal disorder (FSIAD), comprising administering a dual-release drug delivery system according to any one of claims 1 to 10 to a subject.
  12. A method according to claim 11, wherein the peak free testosterone level in the subject after administration is 0.3-2%, preferably 0.5-2%, of the peak total testosterone and/or; and the peak serum free testosterone level in the subject after administration is 0.01 to 0.1 ng/mL, preferably 0.025 to 0.1 ng/mL.
  13. A method according to claim 11 or 12, wherein at least 50%, preferably at least 70%, of the second active ingredient is released within 5 minutes, preferably within 3 minutes, more preferably within 1 minute, for example, within 90 seconds after administration.
  14. A method according to any one of claims 11 to 13, wherein administration comprises maintaining the dual-release drug delivery system under the tongue for at least 30 seconds, preferably at least 60 seconds, e.g., at least 90 seconds, before the subject swallows the dual-release drug delivery system.
  15. A method according to any one of claims 11 to 14, wherein the total plasma concentration of the second active ingredient peaks within 1 hour after administration, preferably within 30 minutes; and the plasma concentration of the first active ingredient peaks between 3 and 6 hours after administration, preferably between 3 and 5 hours, for example between 3 and 4 hours.
  16. A pharmaceutical composition comprising a steroid, such as testosterone or a functional analog or derivative thereof, in combination with a PDE5 inhibitor, such as sildenafil, wherein the testosterone or a functional analog or derivative thereof is present in an amount of 1 mg or more, for example 1-5 mg, preferably 1-4 mg of testosterone.
  17. A pharmaceutical composition according to claim 16, comprising an amount of testosterone or a functional analog or derivative thereof equivalent to 1 mg, 2 mg, 3 mg, or 4 mg of testosterone; and 25 mg or more, 50 mg or more, e.g., 50 mg, 75 mg, or 100 mg of sildenafil.
  18. In paragraph 16 or 17, the composition A core comprising cellulose, a filler selected from organic and/or inorganic salts, and a PDE5 inhibitor for delayed immediate release, preferably sildenafil; A separation coating surrounding the core and comprising a hydrophobic polymer and a hydrophilic material; and A pharmaceutical composition comprising an outer coating surrounding a separation coating and containing testosterone or a functional analog or derivative thereof for immediate release.
  19. A pharmaceutical composition according to any one of claims 16 to 18, wherein the delayed release of the PDE5 inhibitor is an immediate release occurring between 1.5 and 6 hours, preferably between 2.5 and 3.5 hours, after the release of testosterone or a functional analog or derivative thereof.
  20. A pharmaceutical composition according to any one of claims 16 to 19, wherein testosterone or a functional analog or derivative thereof is administered sublingually.

Description

Drug delivery system for the treatment of female sexual interest and arousal disorders The present invention relates to the field of drug formulations and drug delivery for female sexual interest/excitation disorder (FSIAD). The invention is particularly concerned with the effect of a combination of testosterone or its analogues with a PDE5 inhibitor on the sexual desire (and related performance, such as sexual/physical arousal and pain, for example) of female subjects with FSIAD. The invention also relates to a method for enhancing female sexual desire in the treatment of FSIAD, an algorithm useful for determining the dosage of such drug formulations and delivery systems for specific patient groups, and a method for determining an appropriate (initial) dosage and, if necessary, optimizing subsequent dosages. Sexual interest refers to the motivation to engage in sexual activity. It is also commonly referred to as "desire," "sex drive," and "sexual appetite," and describes the sexual emotion that motivates an individual to pursue certain types of sexual activity, whether with a partner or alone. Sexual arousal is conceptualized as the second phase of the sexual response cycle and is defined as both a physical and mental state of readiness for sexual activity. Physiological changes (e.g., erection in men, vaginal dilation and lubrication in women) occur in the body to prepare for sexual interaction. Low sexual desire is the most common sexual dissatisfaction among women. As a result, many women experience sexual dissatisfaction and related distress, which often negatively impairs their quality of life. Female Sexual Interest/Arousal Disorder (FSIAD) refers to a lack of or significantly reduced sexual interest or arousal in women. Typical symptoms of FSIAD may include: absence or reduced interest in sexual activity; absence or reduced sexual thoughts or fantasies; absence or reduced initiation of sexual activity, and typically unacceptability to a partner's attempts at initiation; absence or reduced sexual arousal or pleasure in almost all sexual encounters; absence or reduced sexual interest or arousal in response to any internal or external sexual cue; and absence or reduced genital or non-genital sensation during sexual activity in all or almost all sexual encounters. Typically, in patients with FSIAD, these symptoms have caused clinically significant distress and have persisted for at least six months. Disorders are subdivided by severity level and subdivided into lifelong versus acquired, and generalized versus situational. Previous studies have investigated the prevalence of low sexual interest and low sexual arousal in women. One of the most frequently cited prevalence studies found that 22% of women in the general U.S. population exhibited low sexual interest (Laumann, Paik, Rosen, & Page, 1999). In a survey of women in 29 countries, the self-reported rate of low sexual interest ranged from 26% to 43% (Laumann et al., 2005). When considering the level of distress, the rate may range from 7.3% (Bancroft, Loftus, & Long, 2003) to 23% (Witting et al., 2008), depending on the woman's age, cultural background, and reproductive status. The FDA's new diagnostic guidelines for FSIAD integrate two previously separate diagnoses: Hypoactive Sexual Desire Disorder (HSDD) and Female Sexual Arousal Disorder (FSAD). Treatment for FSIAD may include psychotherapy and/or medication. Currently, drug treatments available worldwide for women with FSIAD are limited. When evaluating the efficacy of various FSIAD treatments, women's sexual characteristics, particularly desire, often require careful consideration of their multifactorial nature; single-item scales such as the Satisfying Sexual Event (SSE) are often oversimplified and fail to reflect the subtle and multidimensional subjective issues that contribute to the composition of sexual desire. Therefore, it would be highly desirable to provide a safe and effective drug delivery system for FSIAD treatment while focusing on effectively enhancing the patient's sexual desire. Furthermore, it is desirable to provide practical guidelines for determining the (starting) dose of this drug delivery system (pharmaceutical composition) for patients, and to provide additional pharmaceutical compositions that can meet the needs of patients who may have special requirements. Summary of the Invention The present invention provides a novel drug delivery system that is effective in enhancing sexual desire in the treatment of FSIAD, particularly acquired FSIAD, without serious side effects. In the context of the present invention, enhancing sexual desire includes increasing an individual’s sexual interest, thoughts, and/or arousal, reducing sexual anxiety and/or distress, promoting sexual and physical arousal, as well as other physical and psychological activities that prepare the individual physically and/or mentally for sexual activity. The drug delivery system of the present invention i