WO2000078323A1 - Utilisation de l'icariine dans la preparation de medicaments pour la prevention et le traitement de troubles de l'erection et de maladies vasoconstrictrices - Google Patents

Utilisation de l'icariine dans la preparation de medicaments pour la prevention et le traitement de troubles de l'erection et de maladies vasoconstrictrices Download PDF

Info

Publication number
WO2000078323A1
WO2000078323A1 PCT/CN2000/000161 CN0000161W WO0078323A1 WO 2000078323 A1 WO2000078323 A1 WO 2000078323A1 CN 0000161 W CN0000161 W CN 0000161W WO 0078323 A1 WO0078323 A1 WO 0078323A1
Authority
WO
WIPO (PCT)
Prior art keywords
icariin
penile
effect
penis
pharmaceutical composition
Prior art date
Application number
PCT/CN2000/000161
Other languages
English (en)
Chinese (zh)
Inventor
Zhongcheng Xin
Original Assignee
Zhongcheng Xin
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Zhongcheng Xin filed Critical Zhongcheng Xin
Priority to AU53867/00A priority Critical patent/AU5386700A/en
Priority to JP2001504386A priority patent/JP4864259B2/ja
Publication of WO2000078323A1 publication Critical patent/WO2000078323A1/fr

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/29—Berberidaceae (Barberry family), e.g. barberry, cohosh or mayapple
    • A61K36/296—Epimedium
    • 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
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
    • 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
    • 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
    • A61P15/08—Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
    • 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
    • A61P15/10—Drugs for genital or sexual disorders; Contraceptives for impotence
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/08—Vasodilators for multiple indications

Definitions

  • icariin in the preparation of a medicament for the prevention or treatment of sexual dysfunction and vasoconstriction-related diseases
  • the present invention relates to the use of icariin in the preparation of a medicament for the prevention and treatment of sexual dysfunction, as well as the use in improving diseases related to vasoconstriction.
  • the sexual function of men is mainly in the presence of various sexual stimuli, under the regulation of the neuro-endocrine system, through the complex physiological response of the vascular system to make the penis erect.
  • This penile erection process first depends on the dilatation of the penile arterioles to increase the penile blood flow, and the penile cavernous smooth muscles relax and the cavernous pores swell, which promotes a further increase in blood flow and guides the increase in penile sponge internal pressure.
  • penile corpus cavernosum smooth muscle plays a key role in this penile erection process, and the penile erection process is regulated by the neuroendocrine system.
  • Animal experiments show that many local distribution factors affect penile erectile function such as norepinephrine (NA), neuropeptide Y (NPY), Acetylcholine (Ach), prostaglandin (PGE), serotonin (5-HT), calcitonin gene-related peptide (CGRP), vasoactive intestinal peptide (VIP), endothelin (EDRF), etc.
  • NA norepinephrine
  • NPY neuropeptide Y
  • Ach Acetylcholine
  • PGE prostaglandin
  • 5-HT serotonin
  • CGRP calcitonin gene-related peptide
  • VIP vasoactive intestinal peptide
  • EDRF endothelin
  • NO nitric oxide
  • PDE tablet acid diesterase
  • Sexual dysfunction can be divided into hyposexuality, erectile dysfunction, orgasmic disorder and ejaculation disorder.
  • the causes of sexual dysfunction include vascular neuropathy, endocrine, psychological lesions, diabetes, hypertension, spinal nerve injury, smoking and other factors can cause sexual dysfunction.
  • vasodilators such as aparvarin
  • fento Drugs such as phentolamine and prostajlandin El are directly injected into the penile cavernous body to treat penile erectile dysfunction to obtain satisfactory results.
  • this therapy can cause side effects such as localized pain, persistent penile erections, and penile fibrosis, so it is often restricted in clinical use.
  • Epimedium is often used as an ingredient in the prescriptions of nourishing and strengthening agents in the traditional medical field, but its mechanism of action has not yet been clarified.
  • Recent research on the effective ingredients of Epimedium has proved that Epimedium contains many ingredients, such as icariin, volatile oil, wax alcohol, predane, plant alcohol, tannin, linoleic acid, etc.
  • icariin A, epimedin A, B, C, quercetin, dehydrated icariin -3-0-rhamnoside, etc. have been isolated.
  • icariin is currently only used as a standard reagent for the analysis of icariin.
  • the object of the present invention is to find and develop new medical uses of icariin
  • icariin has an unexpectedly strong relaxing effect on the smooth muscle of the penile cavernous body and a mild relaxing effect on aortic smooth muscle. Its pharmacological effect and the nitric oxide (NO)-cGMP pathway in smooth muscle cells Related to enhanced activity. It can be used to improve and enhance the erectile function of the penis and improve the symptoms of diseases related to vasoconstriction.
  • NO nitric oxide
  • the present invention relates to the use of icariin in the preparation of a medicament for the prevention of the treatment of sexual dysfunction and the use in the improvement of diseases related to vasoconstriction.
  • the present invention relates to the next test.
  • the present invention relates to the use of icariin in the preparation of a medicament for the prevention and treatment of sexual dysfunction, and the use of the medicament for the preparation and improvement of vasoconstriction-related diseases.
  • the present invention relates to a method for preventing or treating sexual dysfunction and vasoconstriction-related diseases.
  • a pharmaceutical composition comprising icariin as an active ingredient and a pharmaceutically acceptable carrier and excipient.
  • the present invention relates to a method for preventing or treating sexual dysfunction and vasoconstriction-related diseases, which comprises preventing or treating an effective amount of icariin or icariin-containing Pharmaceutical composition.
  • Icariin is a flavonoid glycoside monomer isolated from the crude drug Epimedium. Its chemical structural formula is C 33 H 4 . 0 15 , molecular weight: 676. 67, melting point: 225-230 ° C.
  • icariin used in the present invention may be used alone or in the form of a pharmaceutical composition.
  • the pharmaceutical composition includes icariin as an active ingredient and a pharmaceutically acceptable carrier.
  • the pharmaceutical composition of the present invention can be prepared according to methods known in the art and can be administered orally or parenterally.
  • Oral preparations include, for example, tablets, chews, capsules, suspensions, solutions, etc.
  • parenteral preparations include, for example, injection solutions.
  • Topical preparations include, for example, creams, ointments, patches, sprays and the like.
  • icariin is obtained from the icariin drug by an organic solvent or a mixture of an organic solvent and water.
  • Organic solvents that can be used include alcohols such as methanol, ethanol, etc., alkanes such as dichloromethane, chloroform, ethers such as diethyl ether, ketones such as acetone, lipids such as methyl acetate, ethyl acetate, and hydrocarbons such as hexane Wait.
  • the crystal was colored in UV, and the Pauly reagent was positive.
  • the Rf value of the TLC analysis was 0.6, and the melting point was 239. C. It was confirmed to be pure icariin (icariin, the content of icariin was 99.8% by HPLC analysis).
  • the sexual function of men is mainly to stimulate penile erection through the complex physiological response of the vascular system under the regulation of the neuro-endocrine system under various sexual stimuli.
  • This penile erection process first depends on the dilatation of the penile arterioles and the smooth muscle relaxation of the corpus cavernosum, and the expansion of the corpus cavernosal sinuses promotes an increase in blood flow to the corpus cavernosum, which leads to an increase in the pressure of the corpus cavernosum and compresses the white membrane
  • the lower veins block blood flow, which causes the blood in the penile cavernous body to fill and the penis to harden and erect.
  • the cGMP in the penile cavernous body is again inactivated by the tablet type V enzyme. Therefore, drugs that promote the increase in NO production in the smooth muscle of the penis sponge body, or promote the activity of guanylate cyclase, or inhibit the activity of phosphodiesterase, can increase the synthesis or activity of cGMP, and promote sexual erectile dysfunction. Therapeutic effect. It is an effective experimental method to study the erectile function of the drug penis by using in vitro experiments on the tissues of the sponge body of the penis to observe the effect of the drug on its tonicity, or to determine the effect of the drug on the diabolase.
  • mice Male rabbits (New Zealand rabbits, body weight: 2.5-3.0 kg) were used to isolate penile sea surface smooth muscle, and the pharmacological and pharmacodynamic experiments of icariin were performed in vitro. A total of 60 rabbits were used. The effects of different concentrations of icariin on the tension of smooth muscle in the penile sea surface were observed, and the effect of icariin on the tension of abdominal aorta smooth muscle was observed. In order to study the pharmacological mechanism of the effect of icariin on the relaxation of penile sea surface smooth muscle, atropine, a prostaglandin E1 inhibitor, indomethacin, a prostaglandin E1 inhibitor, was observed.
  • Rabbits were anesthetized with sodium pentobarbital (30-50mg / kg) after resection of the penis and abdominal aorta, and continued to supply 95% oxygen and 5% carbon dioxide mixed gas and filled with Tyrode nutrient solution and maintained a constant temperature of 37.5 ° C
  • the penis cavernosa was separated into muscle strips of 2x2x6mm size, and 4 bands wide arterial rings were separated in the aorta. Each of them contained 10 ml of Tyrode solution and continuously supplied 95% oxygen and 5% carbon dioxide mixed gas.
  • one end is fixed at the bottom, and the other end is connected to the force displacement transducer.
  • each smooth muscle strip or ring was kept at an interval of 30 minutes in order to restore the tension of the penile sponge strip and the arterial ring to a quiet state before proceeding to the next experiment.
  • g7 concept has choline (NANC) nerves antagonist atropine (10- 6 M) Effect of relaxing effects of icariin corpus cavernosum due to the article
  • the penile cavernous body strips were induced by phenylephrine (PZE; 5 X 10—). While maintaining the platform, the various agents were used in accordance with after each concentration were put, wait 20 minutes, and then the male beans saponin in an amount of increasing concentrations (icariin 10- 1Q - 1 ( ⁇ ) are sequentially input, and to observe all of the smooth muscle concentration icariin Relaxing effect. Compared with the degree of relaxation before the penetration of various agents, analyze its effect on the relaxing effect of icariin on the penile cavernous strips of the penis. Observe the drug effects of at least 5 muscle strips or muscle rings of each animal and For statistical analysis.
  • the change of smooth muscle tension under different drug concentrations was analyzed by log attenuation.
  • the half effective concentrations (EC 5 ) of icariin crude in the corpora cavernosa and arterial rings were 4. 08mg / ml, 22. 4mg / ml.
  • the half effective concentrations (EC 5 ) of icariin in corpora cavernosa and arterial rings are 4. 67x10 4 M, 2. 83x10.
  • Calculated according to the content of icariin in the crude icariin (IRF) 8% can be obtained in terms of a concentration of icariin 4. 08x10- 4 M, 2. 64xlO " 3 M, this results EC50 of icariin (EC 50) 4. 67xlO" M , 2.
  • the effect of the relaxation effect caused by the penile cavernous body strips indicates that icariin has been used in the treatment of N w -nitric-L-arginine (L-NNA) (10 4 M) and pyrogallol (10— 4 M)
  • the relaxation effect caused by the pre-treated penile cavernous body strip was significantly suppressed compared with the control group (p ⁇ 0.001), which indicates that this relaxation effect is related to NO production or NO activation.
  • the results are shown in Table 3.
  • Phosphodiesterase V is distributed not only in the corpora cavernosa, but also in platelets. Use Phosphodiesterase type V is isolated from platelets, and analyzing the effect of drugs on its activity is a routine experimental method. The method is to centrifuge fresh human blood (360 gm) for 10 minutes (360 g) to obtain platelet-rich plasma (PRP), and then centrifuge PRP (1400 g) for 10 minutes to precipitate platelets. Take 1ml of precipitated platelets, mix with water-cooled buffer (Hepes 20nM, Sucrous 0. 25M, EDTA ImM, benzylsulfonyl fluoride (PMSF) ImM, pH 7.
  • water-cooled buffer Hepes 20nM, Sucrous 0. 25M, EDTA ImM, benzylsulfonyl fluoride (PMSF) ImM, pH 7.
  • a Mono-Q column (5ml X 50mm), 5ml of buffer A and 10ml of buffer B were repeatedly washed, and telecentric separation (165. 000g) was obtained. 10 ml of the supernatant was placed in a Mono-Q column and the flow rate was set at 1 ml / min. Then, the active ingredients of the complex enzyme were passed through a linear gradient salt (0-0. 5M NaCl) at a flow rate of 1 ml / min to analyze various enzyme components. The activity of each of the obtained enzyme components was measured, and the active enzyme components were collected and put into a liquid nitrogen bottle for later use.
  • a linear gradient salt 0-0. 5M NaCl
  • the phosphodiesterase activity analysis was performed at a final reaction volume of 0.5 ml, and preparations were made on water from the time the enzyme was added to the start of the reaction.
  • Analytical buffer Tris 40mM pH 8. 0, MgCl 2 10 mM, BSA 0.125mg / ml, 2-mercaptoethanol 3. 75 mM
  • the reactant [2H ] cGMP (ca. 28 ci / mmol; ca. 100, 000 ⁇ / 100 ⁇ ) is prepared in advance with analytical buffer.
  • the PDE V activity detection method is a two-step analysis method using [3H] cGMP labeled isotopes.
  • the [3H] cGMP 200 ⁇ was added to the measurement cuvette, the test substance is added (icariin 10- 1Q M- 10- 4 ⁇ ) or control with the same amount of DMS0) 100 ⁇ and purified diester monument Enzyme 100 ⁇ , add buffer to 0.5 ml, and react at 30 ° C for 20 minutes. Immerse in boiling water to stop the reaction. After the reaction was completed, 100 L (lmg / ml) of snake venom (Ophiophagus Hannah; Sigma Chemical Co) was added to the test tube and incubated at 30 ° C for 10 minutes at constant temperature to convert [3H] 5-GMP to [3H] guanosine.
  • the converted [3H] guanosine was analyzed in an AG1-X2 resion (Bio-Rad) reactor using NaOH (0. 1 N) in ion exchange column chromatography to analyze the eluted sample. The radioactivity was measured to analyze phosphoric acid. The activity of diesterase V,
  • the sexual function scores after treatment were respectively: the icariin group was 3.32 ⁇ 0.39, the placebo was 2.04 ⁇ 0.63, and the erection frequency of the penis could be evaluated in the erection of the erection.
  • the glucoside group was 3.11 ⁇ 0.32, the placebo was 2.07 ⁇ 0.88, and the frequency of penile insertion and maintenance of erections during intercourse was 3.18 ⁇ 0.47 in the icariin group, 2.17 ⁇ 0.97 in placebo, and penile erection and erection during intercourse.
  • the icariin group was 3.25 ⁇ 0.43
  • the placebo was 2.18 ⁇ 0.92
  • the sexual satisfaction score was 3.36 ⁇ 0.47
  • the placebo was 2.14 ⁇ 0.95.
  • the score of the glycoside tablet group was significantly higher than the placebo (p ⁇ 0.01).
  • the overall clinical effect was 75.4% and 35.4% in the icariin tablet group and placebo, respectively. No significant side effects were found except for 4 patients with mild gastrointestinal reactions. There were no significant differences in clinical outcomes and side effects in patients with diabetes, hypertension, and heart disease. The results are shown in the table below.

Abstract

L'invention concerne une utilisation de l'icariine dans la préparation de médicaments pour la prévention et le traitement de troubles de l'érection et de maladies vasoconstrictrices.
PCT/CN2000/000161 1999-06-17 2000-06-16 Utilisation de l'icariine dans la preparation de medicaments pour la prevention et le traitement de troubles de l'erection et de maladies vasoconstrictrices WO2000078323A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
AU53867/00A AU5386700A (en) 1999-06-17 2000-06-16 A use of icariin in preparing the medicine for preventing and treating sexual disorder and vasoconstrictive diseases
JP2001504386A JP4864259B2 (ja) 1999-06-17 2000-06-16 性機能障害および血管収縮に関する疾患の予防および治療におけるイカリンの使用

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
KR1999/22665 1999-06-17
KR19990022665 1999-06-17

Publications (1)

Publication Number Publication Date
WO2000078323A1 true WO2000078323A1 (fr) 2000-12-28

Family

ID=19592994

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2000/000161 WO2000078323A1 (fr) 1999-06-17 2000-06-16 Utilisation de l'icariine dans la preparation de medicaments pour la prevention et le traitement de troubles de l'erection et de maladies vasoconstrictrices

Country Status (5)

Country Link
JP (1) JP4864259B2 (fr)
KR (1) KR100394329B1 (fr)
CN (1) CN1199647C (fr)
AU (1) AU5386700A (fr)
WO (1) WO2000078323A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR100394329B1 (ko) * 1999-06-17 2003-08-09 북경동방백오의약개발유한공사 성기능장애 및 혈관계질환의 치료용 약제학적 조성물
JP2011079853A (ja) * 2002-05-10 2011-04-21 Indena Spa 男性および女性の性交不能の処置に有用な配合剤

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ITMI20031427A1 (it) * 2003-07-11 2005-01-12 Indena Spa Combinazioni di agenti vasoattivi, loro uso in campo farmaceutico e cosmetico e formulazioni che li contengono
KR100821683B1 (ko) * 2006-11-01 2008-04-15 우석대학교 산학협력단 이카리사이드 Ⅱ (ｉｃａｒｉｓｉｄｅ Ⅱ)를 유효성분으로 하는 혈관 형성 장애 관련 질환의 예방 및 치료용 조성물
CN102335269B (zh) * 2007-11-21 2013-06-19 客乐谐制药株式会社 芳香酶抑制剂
US8530433B2 (en) 2008-06-13 2013-09-10 Bjo-Biomed Ltd Use of icariside II in manufacture of products for preventing or treating male or female sexual dysfunction
KR101019340B1 (ko) 2008-07-07 2011-03-07 전북대학교산학협력단 복분자 효능 확인 방법

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2000319191A (ja) * 1999-03-05 2000-11-21 Takeda Chem Ind Ltd サイクリックｇｍｐ特異的ホスホジエステラーゼ阻害剤および性的機能障害改善薬
KR100394329B1 (ko) * 1999-06-17 2003-08-09 북경동방백오의약개발유한공사 성기능장애 및 혈관계질환의 치료용 약제학적 조성물

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
GUAN LI-XIN ET AL.: "Vasodilating mechanism of epimedium icariine", CHINESE PHARMACOLOGICAL BULLETIN, vol. 12, no. 4, 1996, pages 320 - 332 *
LI WEN-KUI ET AL.: "Brief introduction to the study of icariine in China", NORTHWEST PHARMACY JOURNAL, vol. 10, no. 3, 1995, pages 138 - 141 *
XIONG YUE-BIN ET AL.: "The effect of extracts from herba epimedii and semen cuscutae on the function of male reproduction", CHINA PHARMACY JOURNAL, vol. 29, no. 2, 1994, pages 89 - 90 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR100394329B1 (ko) * 1999-06-17 2003-08-09 북경동방백오의약개발유한공사 성기능장애 및 혈관계질환의 치료용 약제학적 조성물
JP2011079853A (ja) * 2002-05-10 2011-04-21 Indena Spa 男性および女性の性交不能の処置に有用な配合剤

Also Published As

Publication number Publication date
KR100394329B1 (ko) 2003-08-09
JP4864259B2 (ja) 2012-02-01
KR20010029802A (ko) 2001-04-16
CN1282584A (zh) 2001-02-07
AU5386700A (en) 2001-01-09
JP2003502376A (ja) 2003-01-21
CN1199647C (zh) 2005-05-04

Similar Documents

Publication Publication Date Title
CA2219502C (fr) Procede et formulations servant a moduler la reaction sexuelle chez l'homme ou la femme
RU2313357C2 (ru) Лекарственные формы, полезные для лечения мужской и женской импотенции
US6338862B1 (en) Composition and method of use in treating sexual dysfunction using cGMP-specific phosphodiesterase type 5 inhibitors
CN100522178C (zh) 用于治疗男性和女性性无能的制剂
WO2000078323A1 (fr) Utilisation de l'icariine dans la preparation de medicaments pour la prevention et le traitement de troubles de l'erection et de maladies vasoconstrictrices
US20020013280A1 (en) Pharmaceutical composition for preventing and treating sexual dysfunction and vasculargenic disease comprising icariin
Macêdo et al. Lippia origanoides essential oil induces tocolytic effect in virgin rat uterus and inhibits writhing in a dysmenorrhea mouse model
KR101072175B1 (ko) 데커신 및/또는 데커시놀 안젤레이트, 또는 데커신및/또는 데커시놀 안젤레이트를 유효성분으로 하는당귀추출물을 포함하는 배뇨장애 치료제 및 부종 치료제조성물
Srivastava Pharmacology: A book of achieving knowledge for drugs
US6916845B2 (en) Method for prevention and treatment of male and female sexual dysfunction
CN112569237B (zh) 伊马替尼及其衍生物与尼古丁或其类似物联用或复方在防治尼古丁成瘾与复吸中的应用
CA2680560C (fr) Utilisation de ginsenoside rg1 et de ses metabolites ginsenoside rh1 et ppt
KR20040018335A (ko) 성 기능 장애의 예방 및 치료에 유용한 약제의 제조에서ｎ-아세틸-ｄ-글루코사민의 용도
TWI235062B (en) A combination of the medicine for the prevention and treatment of sexual disorder and vasoconstrictive diseases
US8530433B2 (en) Use of icariside II in manufacture of products for preventing or treating male or female sexual dysfunction
KR100796005B1 (ko) 시르시마린 또는 시르시마리틴을 함유하는 혈관 평활근이완용 조성물
CN101239074B (zh) 海狗油在制备治疗性功能障碍药物中的应用
RU2519226C1 (ru) Средство для профилактики и лечения андрологических заболеваний и способ его получения
KR20040050396A (ko) 천궁을 이용한 일산화질소 생성제 조성물 및 이를 이용한약품 조성물
KR20230067418A (ko) Lcn2 단백질 또는 그를 코딩하는 폴리뉴클레오티드를 유효성분으로 포함하는 발기부전 예방 또는 치료용 약학 조성물
WO2013042984A2 (fr) Composition pour prévenir et atténuer le dysfonctionnement érectile comportant un extrait de plantes composite
JP2011026306A (ja) ホスホジエステラーゼ５阻害剤とイカリソウを含有する医薬組成物。

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AE AL AM AT AU AZ BA BB BG BR BY CA CH CR CU CZ DE DK DM EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX NO NZ PL PT RO RU SD SE SG SI SK SL TJ TM TR TT TZ UA UG UZ VN YU ZA ZW

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): GH GM KE LS MW MZ SD SL SZ TZ UG ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN GW ML MR NE SN TD TG

121 Ep: the epo has been informed by wipo that ep was designated in this application
DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
ENP Entry into the national phase

Ref country code: JP

Ref document number: 2001 504386

Kind code of ref document: A

Format of ref document f/p: F

REG Reference to national code

Ref country code: DE

Ref legal event code: 8642

122 Ep: pct application non-entry in european phase