WO2014042416A1 - Oral composition containing dapoxetin-free base - Google Patents

Oral composition containing dapoxetin-free base Download PDF

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Publication number
WO2014042416A1
WO2014042416A1 PCT/KR2013/008200 KR2013008200W WO2014042416A1 WO 2014042416 A1 WO2014042416 A1 WO 2014042416A1 KR 2013008200 W KR2013008200 W KR 2013008200W WO 2014042416 A1 WO2014042416 A1 WO 2014042416A1
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Prior art keywords
formulation
dapoxetine
free base
film
mouth
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PCT/KR2013/008200
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French (fr)
Korean (ko)
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전홍렬
이봉상
박수준
차봉근
김준기
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주식회사 씨티씨바이오
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Publication of WO2014042416A1 publication Critical patent/WO2014042416A1/en

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    • 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
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
    • A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
    • 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
    • A61K31/13—Amines
    • A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
    • A61K31/138—Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine
    • 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
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
    • 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
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A61K9/006—Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
    • 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
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1629—Organic macromolecular compounds
    • A61K9/1635—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives

Definitions

  • the present invention relates to oral pharmaceutical preparations, in particular film-like preparations, taken by dissolution or disintegration in the oral cavity, in which the manifestation of the effect is rapid and the taste is improved.
  • Dapoxetine and its pharmaceutically acceptable salts are very useful for the treatment or amelioration of premature ejaculation (see US Pat. No. 7,718,705).
  • Fringe Tablet TM (Jansen Korea Co., Ltd.), which contains dapoxetine hydrochloride as an active ingredient, is currently on the market and should be swallowed at a time to avoid bitterness in the “Usage / Dose” section of the manual and with at least 1 cup of water. It is stated to take.
  • the technical problem to be achieved by the present invention is to provide a pharmaceutical preparation that can be taken by dissolving or disintegrating in the mouth (oral cavity) while reducing the bitter taste while showing the same effect.
  • the present invention provides a pharmaceutical formulation with improved taste that is dissolved or disintegrated in the mouth, characterized in that it comprises a dapoxetine free base as an active ingredient.
  • the present inventors dissolve or disintegrate in the mouth instead of conventional tablets, capsules, and the like to promote the onset time of the preparation of the formulation containing dapoxetine or a pharmaceutically acceptable salt thereof as an active ingredient.
  • the present inventors have experimented with various kinds of other salts and free bases, and as a result, the taste of the dapoxetine free base is dramatically improved, and even when dissolved or disintegrated in the mouth, the treatment effect of premature ejaculation is used. It was an amazing invention that there was no influence.
  • the present invention is a pharmaceutical preparation comprising dapoxetine or a pharmaceutically acceptable salt thereof as an active ingredient and dissolved or disintegrated in the mouth, wherein the active ingredient is dapoxetine free base.
  • dapoxetine or a pharmaceutically acceptable salt thereof as an active ingredient and dissolved or disintegrated in the mouth, wherein the active ingredient is dapoxetine free base.
  • the effect of the present invention is more pronounced in the formulations which are taken by dissolution in the mouth without swallowing.
  • pharmaceutical preparations which are taken by dissolving or disintegrating in the mouth include, for example, film formulations such as ODF; Oral disintegrating tablets; Chewable tablets; Granule formulations (preferably granule formulations which can be taken without water); Formulations in the form of candies; Caramel forms, and the like.
  • the present invention provides a formulation of a film formulation, wherein in the film formulation comprising dapoxetine or a pharmaceutically acceptable salt thereof as the active ingredient, the active ingredient is dapoxetine free base.
  • the film may be referred to as a strip, an orally dissolving film, an orally disintegrating film, or the like, and is dissolved in the oral cavity of the tongue, oral mucosa, and sublingual.
  • Film formulations according to the invention have the advantage that they can be taken without water.
  • the present invention provides a pharmaceutical formulation containing dapoxetine free base, which is taken by dissolution or disintegration in the mouth, characterized by rapid effect expression and improved taste. More preferably, the present invention provides a pharmaceutical preparation containing dapoxetine free base which is taken by dissolution or disintegration in the mouth without swallowing, characterized in that the effect expression is rapid and the taste is improved. Even more preferably the pharmaceutical formulation is a film formulation.
  • ODF formulation film formulation containing dapoxetine hydrochloride or dapoxetine free base was prepared in a conventional manner according to the formulation of Table 1 below.
  • a plasticizer, a sweetening agent, and a surfactant are added to the purified water, followed by stirring to dissolve or disperse the same, followed by addition of dapoxetine free base or dapoxetine hydrochloride to the ultra turrax.
  • T-25, IKA was homogenized at 5,000 rpm for 20 minutes.
  • a polymer was added to this was added a polymer and stirred again, after which a flavor was added.
  • the gas in the film preparation solution was removed under vacuum conditions, cooled to room temperature, and then applied to have a suitable thickness on the PE film. After drying at 80 °C to prepare a film formulation comprising a dapoxetine hydrochloride or dapoxetine free base.
  • the film was then cut to contain 33.6 mg of dapoxetine hydrochloride or 30 mg of dapoxetine free base.
  • Example 1 using dapoxetine free base was superior.
  • Formulations of granule formulations containing dapoxetine hydrochloride or dapoxetine free base were prepared in a conventional manner according to the formulation of Table 2 below.
  • the binder solution was prepared by dissolving polyvinylpyrrolidone in an appropriate amount of purified water. Thereafter, granules were prepared by spraying the binder solution on a mixture of the active ingredient and xylitol in the flow using a fluid bed granulator. Sucrose powder and fragrance were mixed with the prepared granules to prepare a final granule formulation.
  • Oral disintegrating tablets containing dapoxetine hydrochloride or dapoxetine free base were prepared in a conventional manner according to the formulation of Table 3 below.
  • API microcrystalline cellulose
  • anhydrous calcium hydrogen phosphate low-substituted hydroxypropyl cellulose
  • mannitol mannitol
  • sucralose magnesium stearate was added to the mixed powder and further mixed.
  • Tablets were prepared by tableting the obtained mixture with a tableting machine (tableting conditions: tableting pressure 8-10 kN, 200 mg / tablet, round shape).
  • Chewable tablets containing dapoxetine hydrochloride or dapoxetine free base were prepared in a conventional manner according to the formulation of Table 4 below.
  • API, glyceryl monostearate, pregelatinized starch, microcrystalline cellulose, citric anhydride, mannitol, aspartame, menthol powder are mixed in the above ratio, and then magnesium stearate is added to the mixed powder and further mixed. It was. Tablets were prepared by tableting the obtained mixture with a tableting machine (pressing conditions: tableting pressure 12-15 kN, 500 mg / tablet, prototype).
  • Example 1-4 and Comparative Example 1-4 prepared above were performed using 10 adult males aged 27 to 53 years. A five-point scale was used for the evaluation, and when the dose was very good because there was no problem with the taste, five points were used. That is, the better the taste was to give a score close to 5 points, the sum of the scores of 10 people is shown in Table 5.
  • Example 1 Three men aged 31-39 who had less than 2 minutes to ejaculate after vaginal insertion were compared and evaluated.
  • the film formulation of Example 1 or Comparative Example 1 was administered about 1.5 hours before sexual activity, and the premature ejaculation improvement effect of Example 1 was relatively compared to the premature ejaculation improvement effect of Comparative Example 1 (that is, the assessment of Comparative Example 1 Comparing the increase in delay time with the increase in ejaculation delay time of Example 1).
  • Example 1 As a result of the experiment, in all three patients, the effect of improving premature ejaculation of Example 1 and Comparative Example 1 was almost similar.

Abstract

The present invention provides a pharmaceutical preparation comprising dapoxetin or a pharmaceutically acceptable salt thereof, and more particularly to a pharmaceutical preparation in a film formulation, wherein the pharmaceutical preparation is administered by being dissolved or disintegrated in the mouth and is characterized in that it has a dapoxetin-free base as an active ingredient.

Description

다폭세틴 유리염기를 함유하는 경구용 조성물Oral compositions containing dapoxetine free base
본 발명은 효과의 발현이 신속하고, 맛이 개선된, 구강에서 녹이거나 붕해시켜 복용하는 경구용 약학 제제, 특히 필름형 제제에 관한 것이다. The present invention relates to oral pharmaceutical preparations, in particular film-like preparations, taken by dissolution or disintegration in the oral cavity, in which the manifestation of the effect is rapid and the taste is improved.
다폭세틴(dapoxetine) 및 이의 약학적으로 허용 가능한 염은 조루증의 치료 또는 개선에 매우 유용하다 (미국 특허 제7,718,705호 참조).Dapoxetine and its pharmaceutically acceptable salts are very useful for the treatment or amelioration of premature ejaculation (see US Pat. No. 7,718,705).
현재 다폭세틴 염산염을 유효성분으로 포함한 프릴리지정TM(한국얀센사)이 시판 중에 있으며, 이 제품의 경우 설명서의 "용법/용량" 부분에 쓴맛을 피하기 위하여 한번에 삼켜야 하며 최소 1컵의 물과 함께 복용하도록 기재하고 있다.Fringe Tablet TM (Jansen Korea Co., Ltd.), which contains dapoxetine hydrochloride as an active ingredient, is currently on the market and should be swallowed at a time to avoid bitterness in the “Usage / Dose” section of the manual and with at least 1 cup of water. It is stated to take.
따라서 본 발명이 이루고자 하는 기술적 과제는 동일한 효과를 나타내면서도 쓴맛을 줄여 입(구강)에서 녹이거나 붕해시켜 복용할 수 있는 약학 제제를 제공하는 것이다.Therefore, the technical problem to be achieved by the present invention is to provide a pharmaceutical preparation that can be taken by dissolving or disintegrating in the mouth (oral cavity) while reducing the bitter taste while showing the same effect.
상기 기술적 과제를 달성하기 위하여, 본 발명은 다폭세틴 유리염기를 유효성분으로 포함하는 것을 특징으로 하는, 입에서 용해시키거나 붕해시켜 복용하는 맛이 개선된 약학 제제를 제공한다.In order to achieve the above technical problem, the present invention provides a pharmaceutical formulation with improved taste that is dissolved or disintegrated in the mouth, characterized in that it comprises a dapoxetine free base as an active ingredient.
본 발명자들은 다폭세틴 또는 이의 약학적으로 허용 가능한 염을 유효 성분으로 포함하는 제제의 효과발현시작시간(onset time)을 촉진하고자 통상적인 정제, 캅셀제 등의 제형 대신에 입에서 녹이거나 붕해시켜 복용하는 제제를 개발하고자 하였다. 그러나, 기존 시판 제품의 설명서에 나타난 바와 같이 다폭세틴 염산염의 경우 쓴맛으로 인해 입에서 용해/붕해시켜 복용하는 제제를 개발하는 것이 실질적으로 불가능하였다.The present inventors dissolve or disintegrate in the mouth instead of conventional tablets, capsules, and the like to promote the onset time of the preparation of the formulation containing dapoxetine or a pharmaceutically acceptable salt thereof as an active ingredient. An attempt was made to develop a formulation. However, as indicated in the existing commercial product instructions, it was practically impossible to develop a preparation for taking dapoxetine hydrochloride by dissolving / disintegrating in the mouth due to the bitter taste.
이에 본 발명자들은 여러 가지 종류의 다른 염들 및 유리염기를 실험해본 결과 다폭세틴 유리염기를 사용할 경우 그 맛이 획기적으로 개선될 뿐만 아니라, 입에서 용해시키거나 붕해시켜 복용하는 경우에도 조루증의 치료 효과에 영향이 없다는 놀라운 발명을 하였다.Therefore, the present inventors have experimented with various kinds of other salts and free bases, and as a result, the taste of the dapoxetine free base is dramatically improved, and even when dissolved or disintegrated in the mouth, the treatment effect of premature ejaculation is used. It was an amazing invention that there was no influence.
즉, 본 발명은 다폭세틴 또는 이의 약학적으로 허용 가능한 염을 유효 성분으로 포함하고, 입에서 용해시키거나 붕해시켜 복용하는 약학 제제에 있어서, 상기 유효 성분이 다폭세틴 유리염기인 것을 특징으로 하는 약학 제제를 제공한다.That is, the present invention is a pharmaceutical preparation comprising dapoxetine or a pharmaceutically acceptable salt thereof as an active ingredient and dissolved or disintegrated in the mouth, wherein the active ingredient is dapoxetine free base. Provide formulations.
바람직하게, 본 발명의 효과는 삼키지 않고 입에서 용해시켜 복용하는 제제에 있어 더욱 두드러진다.Preferably, the effect of the present invention is more pronounced in the formulations which are taken by dissolution in the mouth without swallowing.
본 발명에 따른, 입에서 용해시키거나 붕해시켜 복용하는 약학 제제로는, 예를 들어, ODF 등의 필름 제형; 구강 붕해정; 츄어블정; 과립 제형(바람직하게는 물 없이 복용할 수 있는 과립 제형); 사탕 형태의 제형; 캐러멜 형태의 제형 등이 있다.According to the present invention, pharmaceutical preparations which are taken by dissolving or disintegrating in the mouth include, for example, film formulations such as ODF; Oral disintegrating tablets; Chewable tablets; Granule formulations (preferably granule formulations which can be taken without water); Formulations in the form of candies; Caramel forms, and the like.
또한, 다폭세틴 염(salt) 대신에 다폭세틴 유리염기를 사용하여 ODF 등의 필름 제형을 제조할 경우 필름의 성상이 더욱 탁월하였으며, 필름을 제조하기가 더욱 용이하였다.In addition, when the film formulations such as ODF were prepared using daxetine free base instead of daxetine salt, the properties of the film were more excellent, and the film was easier to prepare.
따라서, 본 발명은 다폭세틴 또는 이의 약학적으로 허용 가능한 염을 유효 성분으로 포함하는 필름(film) 제제에 있어서, 상기 유효 성분이 다폭세틴 유리염기인 것을 특징으로 하는 필름 제형의 제제를 제공한다.Accordingly, the present invention provides a formulation of a film formulation, wherein in the film formulation comprising dapoxetine or a pharmaceutically acceptable salt thereof as the active ingredient, the active ingredient is dapoxetine free base.
본 발명에 있어 상기 필름은 스트립(strip), 구강용해필름(orally dissolving film), 구강붕해필름(orally disintegrating film) 등으로 명명될 수 있으며, 혀 위, 구강점막, 설하 등 구강 내에 붙여 녹여 복용하는 제형을 말한다. 본 발명에 따른 필름 제형은 물 없이 복용 가능하다는 장점이 있다.In the present invention, the film may be referred to as a strip, an orally dissolving film, an orally disintegrating film, or the like, and is dissolved in the oral cavity of the tongue, oral mucosa, and sublingual. Says the formulation. Film formulations according to the invention have the advantage that they can be taken without water.
본 발명은 효과 발현이 신속하고 맛이 개선된 것을 특징으로 하는, 입에서 용해시키거나 붕해시켜 복용하는 다폭세틴 유리염기 함유 약학 제제를 제공한다. 보다 바람직하게, 본 발명은 효과 발현이 신속하고 맛이 개선된 것을 특징으로 하는, 삼키지 않고 입에서 용해시키거나 붕해시켜 복용하는 다폭세틴 유리염기 함유 약학 제제를 제공한다. 더욱더 바람직하게 상기 약학 제제는 필름 제형이다.The present invention provides a pharmaceutical formulation containing dapoxetine free base, which is taken by dissolution or disintegration in the mouth, characterized by rapid effect expression and improved taste. More preferably, the present invention provides a pharmaceutical preparation containing dapoxetine free base which is taken by dissolution or disintegration in the mouth without swallowing, characterized in that the effect expression is rapid and the taste is improved. Even more preferably the pharmaceutical formulation is a film formulation.
이하, 본 발명의 이해를 돕기 위하여 실시예 등을 들어 상세하게 설명하기로 한다. 그러나, 본 발명에 따른 실시예들은 여러 가지 다른 형태로 변형될 수 있으며, 본 발명의 범위가 하기 실시예들에 한정되는 것으로 해석되어서는 안 된다. 본 발명의 실시예들은 당업계에서 평균적인 지식을 가진 자에게 본 발명을 보다 완전하게 설명하기 위해 제공되는 것이다.Hereinafter, examples and the like will be described in detail to help understand the present invention. However, embodiments according to the present invention can be modified in many different forms, the scope of the invention should not be construed as limited to the following examples. Embodiments of the present invention are provided to more fully describe the present invention to those skilled in the art.
<다폭세틴 함유 ODF 제형의 제조>Preparation of Dapoxetine-Containing ODF Formulations
하기 표 1의 처방에 따라 통상적인 방법으로 다폭세틴 염산염 또는 다폭세틴 유리 염기를 함유하는 ODF 제제(필름 제제)을 제조하였다.An ODF formulation (film formulation) containing dapoxetine hydrochloride or dapoxetine free base was prepared in a conventional manner according to the formulation of Table 1 below.
표 1
Figure PCTKR2013008200-appb-T000001
 Table 1
Figure PCTKR2013008200-appb-T000001
구체적으로 정제수에 가소제(plasticizer), 감미제(sweeting agent) 및 계면활성제(surfactant)를 첨가 후에 교반하여 용해 또는 분산시키고, 여기에 다폭세틴 유리염기 또는 다폭세틴 염산염을 첨가한 후 호모게나이저(Ultra turrax T-25, IKA)를 이용하여 5,000rpm으로 20분간 균질화하였다. 여기에 고분자를 첨가하고 다시 교반하였고, 그 후 향료(flavor)를 첨가하였다. 이후 진공 조건으로 필름 제조액 내의 가스를 제거하고, 실온으로 냉각시킨 후 PE 필름 위에 적당한 두께를 가지도록 도포하였다. 이후 80℃에서 건조하여 다폭세틴 염산염 또는 다폭세틴 유리염기를 포함하는 필름 제제를 제조하였다. 이후 필름당 다폭세틴 염산염 33.6 mg 또는 다폭세틴 유리염기 30 mg이 함유되도록 필름을 절단하였다.Specifically, a plasticizer, a sweetening agent, and a surfactant are added to the purified water, followed by stirring to dissolve or disperse the same, followed by addition of dapoxetine free base or dapoxetine hydrochloride to the ultra turrax. T-25, IKA) was homogenized at 5,000 rpm for 20 minutes. To this was added a polymer and stirred again, after which a flavor was added. Thereafter, the gas in the film preparation solution was removed under vacuum conditions, cooled to room temperature, and then applied to have a suitable thickness on the PE film. After drying at 80 ℃ to prepare a film formulation comprising a dapoxetine hydrochloride or dapoxetine free base. The film was then cut to contain 33.6 mg of dapoxetine hydrochloride or 30 mg of dapoxetine free base.
제조된 필름의 성상 및 필름의 제조 용이성 측면에 있어서 다폭세틴 유리염기를 사용한 실시예 1이 월등히 우월하였다. In terms of the properties of the produced film and the ease of manufacture of the film, Example 1 using dapoxetine free base was superior.
<다폭세틴 함유 과립 제형의 제조>Preparation of Dapoxetine-containing Granule Formulations
하기 표 2의 처방에 따라 통상적인 방법으로 다폭세틴 염산염 또는 다폭세틴 유리 염기를 함유하는 과립 제형의 제제를 제조하였다.Formulations of granule formulations containing dapoxetine hydrochloride or dapoxetine free base were prepared in a conventional manner according to the formulation of Table 2 below.
표 2
Figure PCTKR2013008200-appb-T000002
 TABLE 2
Figure PCTKR2013008200-appb-T000002
구체적으로, 폴리비닐피롤리돈을 적당량의 정제수에 녹여 결합액을 제조하였다. 이후, 유동층과립기(Fluid Bed Granulator)를 사용하여 유동 중인 유효 성분과 자일리톨의 혼합물에 상기 결합액을 분사하여 과립을 제조하였다. 제조된 과립에 슈크로스 파우더와 향료를 혼합하여 최종 과립 제제를 제조하였다.Specifically, the binder solution was prepared by dissolving polyvinylpyrrolidone in an appropriate amount of purified water. Thereafter, granules were prepared by spraying the binder solution on a mixture of the active ingredient and xylitol in the flow using a fluid bed granulator. Sucrose powder and fragrance were mixed with the prepared granules to prepare a final granule formulation.
<다폭세틴 함유 구강 붕해정의 제조><Preparation of oral disintegrating tablet containing dapoxetine>
하기 표 3의 처방에 따라 통상적인 방법으로 다폭세틴 염산염 또는 다폭세틴 유리 염기를 함유하는 구강 붕해정을 제조하였다.Oral disintegrating tablets containing dapoxetine hydrochloride or dapoxetine free base were prepared in a conventional manner according to the formulation of Table 3 below.
표 3
Figure PCTKR2013008200-appb-T000003
 TABLE 3
Figure PCTKR2013008200-appb-T000003
구체적으로, API, 미결정셀룰로오스, 무수인산수소칼슘, 저치환도히드록시프로필셀룰로오스, 만니톨 및 수크랄로스를 상기의 비율로 혼합한 후, 혼합된 분말에 스테아린산마그네슘을 첨가하고 추가로 더 혼합하였다. 수득된 혼합물을 타정기로 타정하여 정제를 제조하였다 (타정조건: 타정압력 8~10kN, 200mg/정제, 원형)Specifically, API, microcrystalline cellulose, anhydrous calcium hydrogen phosphate, low-substituted hydroxypropyl cellulose, mannitol and sucralose were mixed in the above ratio, and then magnesium stearate was added to the mixed powder and further mixed. Tablets were prepared by tableting the obtained mixture with a tableting machine (tableting conditions: tableting pressure 8-10 kN, 200 mg / tablet, round shape).
<다폭세틴 함유 츄어블정의 제조><Production of dapoxetine-containing chewable tablets>
하기 표 4의 처방에 따라 통상적인 방법으로 다폭세틴 염산염 또는 다폭세틴 유리 염기를 함유하는 츄어블정을 제조하였다.Chewable tablets containing dapoxetine hydrochloride or dapoxetine free base were prepared in a conventional manner according to the formulation of Table 4 below.
표 4
Figure PCTKR2013008200-appb-T000004
 Table 4
Figure PCTKR2013008200-appb-T000004
구체적으로, API, 글리세릴모노스테아레이트, 전젤라틴화전분, 미결정셀룰로오스, 무수구연산, 만니톨, 아스파탐, 멘톨파우더를 상기의 비율로 혼합한 후, 혼합된 분말에 스테아린산마그네슘을 첨가하고 추가로 더 혼합하였다. 수득된 혼합물을 타정기로 타정하여 정제를 제조하였다 (타정조건: 타정압력 12~15kN, 500mg/정제, 원형).Specifically, API, glyceryl monostearate, pregelatinized starch, microcrystalline cellulose, citric anhydride, mannitol, aspartame, menthol powder are mixed in the above ratio, and then magnesium stearate is added to the mixed powder and further mixed. It was. Tablets were prepared by tableting the obtained mixture with a tableting machine (pressing conditions: tableting pressure 12-15 kN, 500 mg / tablet, prototype).
<쓴맛 평가><Bitter taste evaluation>
27~53세 성인 남성 10명을 이용하여 상기 제조한 실시예 1-4와 비교예 1-4의 맛 관능평가를 하였다. 평가 시 5점 척도를 사용하였으며, 맛에 문제가 없어 복용성이 매우 양호한 경우에는 5점, 맛이 너무 써 복용이 실질적으로 어려운 경우에는 1점을 주도록 하였다. 즉, 맛이 양호할수록 5점에 가까운 점수를 주도록 하였으며, 10명의 점수 합계를 하기 표 5에 나타내었다.Taste sensory evaluation of Example 1-4 and Comparative Example 1-4 prepared above were performed using 10 adult males aged 27 to 53 years. A five-point scale was used for the evaluation, and when the dose was very good because there was no problem with the taste, five points were used. That is, the better the taste was to give a score close to 5 points, the sum of the scores of 10 people is shown in Table 5.
표 5
Figure PCTKR2013008200-appb-T000005
 Table 5
Figure PCTKR2013008200-appb-T000005
상기 표 5에 나타난 바와 같이, 유효성분으로 다폭세틴 유리염기를 사용할 경우 쓴맛이 획기적으로 줄어드는 것을 알 수 있다.As shown in Table 5, it can be seen that the bitter taste is drastically reduced when using dapoxetine free base as an active ingredient.
<조루증 개선 정도 평가><Evaluation of Premature Ejaculation Improvement>
질 내 삽입 후 사정까지의 시간이 2분 미만인 31~39세의 성인 남자 3명을 대상으로 조루증 개선 정도를 상대적으로 비교 평가하였다. 성행위 약 1.5시간 전에 실시예 1 또는 비교예 1의 필름 제형을 투여하도록 하였으며, 비교예 1의 조루증 개선 효과 대비 실시예 1의 조루증 개선 효과를 상대적으로 비교평가하도록 하였다 (즉, 비교예 1의 사정지연시간 증가 정도와 실시예 1의 사정지연시간 증가 정도를 비교함). Three men aged 31-39 who had less than 2 minutes to ejaculate after vaginal insertion were compared and evaluated. The film formulation of Example 1 or Comparative Example 1 was administered about 1.5 hours before sexual activity, and the premature ejaculation improvement effect of Example 1 was relatively compared to the premature ejaculation improvement effect of Comparative Example 1 (that is, the assessment of Comparative Example 1 Comparing the increase in delay time with the increase in ejaculation delay time of Example 1).
실험결과 3명 모두에 있어 실시예 1과 비교예 1의 조루증 개선 효과가 거의 유사하게 나타났다. As a result of the experiment, in all three patients, the effect of improving premature ejaculation of Example 1 and Comparative Example 1 was almost similar.

Claims (4)

  1. 다폭세틴 또는 이의 약학적으로 허용 가능한 염을 유효 성분으로 포함하고, 입에서 용해시키거나 붕해시켜 복용하는 약학 제제에 있어서,In the pharmaceutical preparation containing dapoxetine or a pharmaceutically acceptable salt thereof as an active ingredient, dissolved or disintegrated in the mouth,
    상기 유효 성분이 다폭세틴 유리염기인 것을 특징으로 하는 약학 제제.Pharmaceutical formulation, characterized in that the active ingredient is dapoxetine free base.
  2. 제1항에 있어서, 상기 약학 제제는 삼키지 않고 입에서 용해시켜 복용하는 것을 특징으로 하는 약학 제제.The pharmaceutical formulation of claim 1, wherein the pharmaceutical formulation is dissolved in the mouth without swallowing.
  3. 제1항에 있어서, 상기 제제는 필름, 구강 붕해정, 츄어블정, 과립, 사탕 또는 캐러멜 제형인 것을 특징으로 하는 약학 제제.The pharmaceutical formulation of claim 1, wherein the formulation is a film, oral disintegrating tablet, chewable tablet, granule, candy or caramel formulation.
  4. 제3항에 있어서, 상기 제제는 필름 제형인 것을 특징으로 하는 약학 제제.The pharmaceutical formulation of claim 3, wherein the formulation is a film formulation.
PCT/KR2013/008200 2012-09-13 2013-09-11 Oral composition containing dapoxetin-free base WO2014042416A1 (en)

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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1225881B1 (en) * 1999-09-03 2006-02-22 APBI Holdings, LLC The use of dapoxetine, a rapid-onset selective serotonin reuptake inhibitor, for treating sexual dysfunction
WO2008035358A2 (en) * 2006-06-05 2008-03-27 Cadila Healthcare Limited Process for preparing dapoxetine
US20110129519A1 (en) * 2006-08-14 2011-06-02 Katzman Daniel E Modafinil-Based Treatment For Premature Ejaculation
WO2012053006A2 (en) * 2010-10-18 2012-04-26 Panacea Biotec Ltd Improved oral fast dissolving films comprising combination of polymers and method of preparation thereof
KR20120068678A (en) * 2010-09-17 2012-06-27 에스케이케미칼주식회사 (s)-n,n-dimethyl-3-(naphthalen-1-yloxy)-1-phenylpropan-1-amine derivatives, pharmaceutical compositions containing them, and manufacturing methods thereof

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1225881B1 (en) * 1999-09-03 2006-02-22 APBI Holdings, LLC The use of dapoxetine, a rapid-onset selective serotonin reuptake inhibitor, for treating sexual dysfunction
WO2008035358A2 (en) * 2006-06-05 2008-03-27 Cadila Healthcare Limited Process for preparing dapoxetine
US20110129519A1 (en) * 2006-08-14 2011-06-02 Katzman Daniel E Modafinil-Based Treatment For Premature Ejaculation
KR20120068678A (en) * 2010-09-17 2012-06-27 에스케이케미칼주식회사 (s)-n,n-dimethyl-3-(naphthalen-1-yloxy)-1-phenylpropan-1-amine derivatives, pharmaceutical compositions containing them, and manufacturing methods thereof
WO2012053006A2 (en) * 2010-10-18 2012-04-26 Panacea Biotec Ltd Improved oral fast dissolving films comprising combination of polymers and method of preparation thereof

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