TW200407149A - Methods of treatment of male erectile dysfunction - Google Patents

Abstract

The invention provides methods for the treatment of erectile dysfunction in a patient suffering from a co-morbid condition comprising placing in the fossa navicularis of the patient an erection-inducing amount of a semi-solid vasoactive prostaglandin composition.

Description

200407149 A7 B7 V. Description of the invention (Printed by the Consumer Cooperative of Intellectual Property Bureau of the Ministry of Economics [Technical Field to which the Invention belongs] The present invention is related to the treatment of I1 early dysfuction due to the erectile dysfunction of patients with two or more diseases [Prior art] "Impotence" — The word is used to indicate that men cannot reach and maintain penile erections enough to allow satisfactory sexual intercourse. "Erectile function P early obstruction" Ichioka's more precise wording is "indicating that males have no The ability to reach an erectile penis as part of the multifaceted process of male sexual function ", see Droller, M.J. et al. Statement of the Common Opinion Development Meeting on Impulse in the National Institutes of Health (1 993) (Impotence Consensus Development Conference Statement) 〇 Erectile dysfunction may be due to psychological reasons (mental erectile dysfunction) or organic causes or both. Organic causes include physiological, neurological, vascular, and hormonal pathologies or Combine the above pathologies. • The normal physiology of an erection includes nerve impulses. Certain muscles relax. These muscles restrict blood flow through the arteries in the penis when contracted. When relaxed, the muscles allow the blood flow to increase. 'Increased blood flow fills the three groups of erectile tissue in the penis with blood.' Less flaccid, congested erectile tissue and muscle structure of the penis suppress adjacent veins, restrict blood flow from the penis, the restriction of blood flow from the vagina increases and persists an erection. ^ Lack of certain hormones such as androgen (testosterone), or Increase: Other hormones such as prolactin can cause erectile dysfunction. Many drugs such as diuretics, antihypertensive agents, addictive narcotics, alcohol, and psychotropic drugs, etc. J effects can cause erectile dysfunction. See MU ρ3 y, p. (Please read the precautions on the back before filling this page} Order · 0 m 4 200407149

et al. American Journal of Medical Science (Amer · j. Medical 309: 99-1 09 (1 995). 'Neurological and vascular damage may also be an organic cause of erectile dysfunction, and the disease process may include several aspects, For example, diabetes, which can cause damage to both nerves and blood vessels, can cause erectile dysfunction. A large percentage of male diabetic patients suffer from erectile dysfunction. Although diabetes is erectile dysfunction; ED) is a common risk factor, however, the pathology of erectile dysfunction in diabetes has not been fully understood. '[Reference Sullivan, M.E. et al., Changes in Endothelium B Receptors in Diabetic Rabbits in the Sea: Potential Associations The pathogenesis of erectile dysfunction (Alterations in endothelin B receptor sites in cavernosal tissue of diabetic rabbits: potential relevance to the pathogenesis of erectile dysfunction). J. Urol. 1997 158 (5): 1 96 6-72. Erectile dysfunction may be just one aspect of diabetes-related vascular disease [Reference Sai ram, K., et a 1 ., Prevalence of undiagnosed diabetes mellitus in male erectile dysfunction, BJU Int. 2001 88 (1): 68-71; Sullivan, ME et al., Nitric oxide and penile erection : Is erectile dysfunction a symptom of another vascular disease? (Nitric oxide and penile erection: is erectile dysfunction another manifestation of vascular disease?), Cardiovasc Res. 1999 Aug 15; 43 (3): 658-65. (Microvasculopathy) is a paper standard for diabetes. Applicable to the Chinese National Standard (CNS) A4 specification (210 × 297 mm) (Please read the precautions on the back before filling out this page). Order printed by the Intellectual Property Bureau of the Ministry of Economic Affairs and Consumer Cooperatives. 200407149 A7 B7 V. Description of the invention () Features' Many studies have shown a link between diabetes, erectile dysfunction and endothelial dysfunction [Ref. DeAngelis, L., et a 1 ·, Erectile dysfunction of type 2 diabetes: a Possible association (Erectile dysfunction in Type II diabetes: a possible 1 ink). Diabeto1〇gia. 20 0 1 44 (9): 1155-60; Burchardt, T ·, etal ·, streptozotocin induced reduction of endothelial and smooth muscle density in the corpora cavermosa of the streptozotocin in diabetic mice induced diabetic rat). J Urol. 2001 164 (5): 1807 -11; Hop frier, R. L., &

Gopalakrishnan, V., Endothelium ... Endothelin: emerging role in diabetic vascular complications. Diabetologia. 1999 42 (12): 1383-94]. In other studies, it has been found that erectile dysfunction is most common among patients affected by cardiovascular disease or diabetes' and that the presence of cardiovascular disease increases the risk of erectile dysfunction [Ref. Sasayama, S., et al. Men's Health Study : Epidemiology of Erectile Dysfunction and Cardiovascular Disease (Men, Health Study. Epidemiology 0f Erectile Dysfunction and Cardiovascular Disease). Circ. J., 2000; 67: 656-659]. Eradication and retrobone prostatectomy (radica 1 retropubic proststectomy) have been the standard treatment for prostate cancer that has been restricted to organs / subjects for decades. After this operation, up to 90% of people have reported erectile dysfunction. The main variables of surgical technique and experience affect the results [see Zippe, CD ·, et al ·, eradication type prostatectomy, and the Zhang scale is applicable to the Chinese National Standard (CNS) M specification (2 丨 〇 > < 297 Gongchu) (Please read the precautions on the back before filling out this page) Order-Printed by the Consumers' Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs, 200407149 A7 B7 V. Description of the Invention (Management of erectile gysfunction folloeing radical prostatectomy),

Current Urology Reports, 2: 495-503 (200 1)]. Age is also a factor. Although approximately 50 to 70% of younger men regain sexual abilities after a neuroprosthetic prostatectomy, the rate of sexual abilities recovery is lower than in patients over 70 years old [Ref Catal ona, W · J ·, Et a 1 ·, Nerve-sparing radical prostatectomy: evaluation of results after 250 patients. J. Urol. 1990; 143: 538-43; discussion 44, Quinlan, D. M., et al., Sexual function after radical prostatectomy: Sexual functión following radical prostatectomy: influence of preservation of neurovascular bundles. J. Urol. 1991; 145 : 998-1002]. Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs, (please read the precautions on the back before filling out this page) Therefore 'Most men need to treat erectile dysfunction in order to have sexual activity after radical prostatectomy to shrink the vacuum. Devices, intravesicular injection of vasoactive drugs, and transurethral vasodilator treatment methods have reported response rates of 50% to 70%, but because of the difficulty of long-term coordination, the interruption rate within a year is close to 50%. Ad hoc recommendations for the treatment of erectile dysfunction include external placement, sexual treatment, surgical implantation of internal artificial substitutes, direct injection of drugs into the penis, and topical use of drugs. None of these methods are completely effective. The outer 4 device includes a tourniquet (see US Patent No. 2,81 8, 855) and a vacuum erectile aid for external application. Although some clinicians believe that the external application of vacuum erectile aids is a household, "the Zhang scale is applicable to the family standard (⑽) Tiege (2 seems to tear the public 200407149 A7) 5. Description of the invention (the first choice of treatment, but some patients do not Willing to use such devices (Reference, eefe, M., et ai. Medical Clinics od No.; th America 79: 415-434 (1995)) 〇 Sexual treatment of symptoms was originally discovered by Masters and Johnsom Effect, but subsequent studies did not show impressive results, and Yunloide's treatment did not present another attractive option for this type of patients (see Vickers, MA, et al. J. Ur〇1 〇gy 149: 1258-1261 (1993)). When printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs ~ surgical implantation mechanical devices such as hinges or solid short rods and expandable ammunition K drives or hydrodynamic artificial substitutes Used for some time. Several penis artificial substitutes have been described as soft plastic elements with a fixed hardness. However, these people are of constant hardness, which causes patient discomfort. Other types of penile artificial substitutes include surgery Pumps are used to create the high hydraulic pressure in elastic silicon coatings (elastlc siUcon mantle). Implant these: Complex devices need to implant several components into the patient, for example, liquid reservoirs, Pumps, several valves, connecting catheters, and the like except for these components, are implanted directly into the penis. Other penile replacements use electricity from an external source and an alternating magnetic field. The source frequency is between 50 and 1.0. 〇〇Hertz (Hz) changes affect the 衮, a component inside the penis, this component senses a magnetic field and causes the internal 'memory' to move from the reservoir to the elastic bag in the sponge: 'and cause the penis to erect Some reports describe that artificial substitutes include a water-permanent magnet that can reciprocate under the influence of this magnetic field so that liquid is pumped from the reservoir to the elastic envelope, so the effect is the same as the internal component sensing the external source. Magnetic field. However, although k-like artificial substitutes can provide sufficient hardness during sexual intercourse, the patient and the 200,407,149 A7 V. Description of the invention Case report also detailed the treatment of single ::: person: not substitutes, • (refer ⑽ ^ ^ intracavernous twenty-two

Impotence Res 4-11S iq〇9 ^ -v '·, Int. J · KK. Σ + l, 1 992) or use MUSE® (see Chew H, & Stuckey, BG A Int T τ 5 to · 1 95-1 96 people ·, mP〇tence Res ·, satisfied. 95 196, 200.) The administration of drugs that attempt to alleviate penile artificial substitutes that do not cause erections and strengthens is described in the Wu Guo patent case-number 4, 127, li8, this method of treating male impotence plus a free-selling dose of 刭 W from ^ a suitable blood vessel to expand into the yin, especially a sympathetic nerve blocker or a flat muscle relaxant To cause and strengthen an erection. One thousand β —- Μ ·· All US patents No. 4, 801,587 An ointment is applied to relieve impotence, and the ointment is composed of papaverine and sodium nitroprusside (s 〇di_ ni ^ roprusside), phenoxybenzamine, or phentolamine, and a carrier are printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs to assist the absorption of major drugs through the skin. EpRashidy's U.S. Patent No. 5,256,652 teaches the use of an aqueous topical composition ' with vasodilators such as papaverin and hydroxypropyl-β-cyclodextrin together. Biochemical, physiological, and clinical effects of cyclic guanosine 3 ', 5'-monophosphate specific phosphodiesterase (cGMP-specific PDE) inhibitors To enable them to be used in a variety of different disease states, among which there is a need to adjust smooth muscle, kidney, hemostasis, inflammation, and / or endocrine function. Especially a homogeneous isomerase This paper size is applicable to China National Standard (CNS) A4 specification (210X297 mm 200407149

(isozyme), the fifth type of CGMP-exclusive phosphodiesterase (pDE5) is the major cGMP hydrolase in vascular smooth muscle, and its performance in the cavernous body of the penis has been reported 'so PDE5 has become a treatment for sexual dysfunction Striking goals. A selective inhibitor of PDE5, sildenafil, has become a marketed drug VI AGRA® 'although sildenaf il has achieved considerable commercial success' but significant side effects include facial flushing (丨 〇% @ rate) and did not meet expectations, these side effects limit the use of sildenafu X in some patients, such as patients with abnormal vision, high blood pressure, and most importantly, patients using organic nitrate drugs (Welds etal ., Amer J. of Cardiology, 83 (5A), pp. 21 (C) -28 (C) (1999)). The use of sildenafil in patients taking organic nitrate drugs is believed to lead to a clinically significant drop in blood pressure 'putting the patient at risk'. Therefore, the packaging labeling of sildenafil provides severe contraindications. Glycerin (nitroglycerin), isosorbide mononitrate, isosorbide dinitrate, erythrityl tetranitrate, and any other form of nitric oxide donor (Nitric oxide donors), whether conventional or intermediate, because sildenafil enhances the blood pressure-lowering effect of nitrates. See C · R. Conti et al ·, Amer. J. 〇f Cardiology, 83 (5A), pp .29 (C) -34 (C) (1999), so although si ldenaf i 1 has its convenience, it still needs to find a more suitable treatment for sexual dysfunction for patients with more than two disease states such as hypertension. Improved drugs. One method is to find other orally-available phosphates with larger selectivity. The paper size is applicable to the Chinese National Standard (CNS) A4 specification (210X297). (Please read the precautions on the back before filling this page.) Printed by the Property Cooperative's Consumer Cooperative, 200407149 A7 B7 V. Description of the invention (Acid lipase-5 inhibitor, which may hopefully not have the side effects of sildenaf II 'See US Patent No. 6,451,807, two such phosphate Dilipase-5 inhibitors are vardenaf (Levitra ™) and tadalafil (ciaHsTM). Early evidence indicates that the other two diabolase-5 inhibitors are important for use. Nitrate-treated (contraindications) patients with angina pectoris and hypertensive patients with alpha-blockers will have the same interactions as combined therapy with sildenaf i 1, see Gresser, U., SGleiter, C.Η., Erectile dysfunction: Comparison of efficacy and side effects of the PDE-5 inhibitors sildenafil, vardenafi 1 and tadalafi1. Review of the literature, European J, Me d. Res ·, 2002, 7: 435-446. 'However, this method of searching for more specific inhibitors cannot necessarily solve the problems caused by oral phosphodiesterase-5 inhibitor therapy, that is, in most erections A significant proportion of patients with dysfunction do not respond to treatment. Another option is to 'look for another class of drugs that act on another target to treat patients with erectile dysfunction who do not have anti-mute against oral phospholipase-5 inhibitors. For Patients with more than two disease conditions, such as those with type A sympathetic blockers, hypertensive patients treated, or patients with angina pectoris' are also looking for alternative treatment options because oral phosphodiesterase- 5Inhibitor treatment is contraindicated or may be warned. / Prostaglandin Ei is a derivative of prostanoic acid, which is a 20-carbon fatty acid, expressed by the following chemical formula: _ 11 This paper size applies to Chinese National Standard (CNS) A4 (210 X 297 mm) (Please read the precautions on the back before filling this page)

, 1T Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs 200407149 A7

This product is available on the market, namely, Chinoin Pharmaceutical and Chemical Factory Co., Ltd. (Budapest, Hungary) under the trade name AlprOStad, U USP, ’and Pharraacia & Upjohn under the trade name Caver ject. The prostaglandin El and α-cyclodextrin (alpha-Cyclodextrin) complex product is alpr〇statUalfadex from Ono Pharmaceutical (Japan), and is made by Schwarz Phanna (Germany) under the trade name "Edex⑧," or "Viradex®" injectable form. In a commercially available dosage form (MUSE®, Vivus Menlo Park CA) 'alpr〇stadil, administered with a 3.2 cm length 3.5 mm diameter Applicator for a hollow straight tube, placing a small pill in the urethra (Padma_Nathan, h et al. 'N. Engl. J. Med., 336: Bu 7 (1 997), Intellectual Property Office, Ministry of Economic Affairs Printed by the Employee Consumer Cooperatives -——...--.___ 12 This paper size applies the Chinese National Standard (CNS) Λ4 specification (see the first figure). In the residential part of the research by Padma-Nathan et al., Use + MUSE® Patients had 32.7% (10.8% of the administration; person C) the main yin was painful @ @ 5.1% had minor urethral trauma, compared with 3.3% and 1.0% of patients in the control group, respectively. Below The frequency of these reported side effects is different: 17 to 23.6% had penile pain, compared with i 7 in the control group and 4.8% of patients with mild urethral bleeding (peters〇n 匸 a et al., J. Ur〇l ·, 1 59: 1523_1 528 ( 1 998))., I .. In a European population study, 31% of MUSE patients reported a burning sensation of burning, '4.8% reported urethral bleeding, and 2 reports =: 200407149 A7 B7 V. Description of the invention () Testicular pain (Porst, H ·, Int · J. Impot · Res ·, 9: 1 87-1 92 (1 997)). Patients who respond to MUSE® treatment are defined as having at least one erection sufficient to complete sexual intercourse. Research reports indicate that The percentages are 43% (Porst, 1 997), 65.9% (Padma-athan etal, 1999 7), and 70.5% (Petersonetal, 1998), although the editorial office's opinion on the latter two studies is considered more appropriate 30 to 40% are reported (Benson, G., J. Urol ·, 159: 1 527-1 528 (1 998)). It has been reported that a 1 ml of polyethylene glycol is given to the urethra ) A preparation containing 1 mg of prostaglandin Ei in phosphatidylchol ine 1 iposomes is compared with broccoli Exit prostaglandin Ει, display relatively ineffective (Englehardt, P.F ·, et al ·, British J · Urology, 81: 441-444, 1 9 98). None of the patients with erectile dysfunction who received liposomal preparations achieved complete penile rigidity, and only 6 of the 25 patients had achieved an erection sufficient to be inserted into the vagina. On the contrary, the injection of prostaglandin L in the cavernous body is printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs among 25 patients with the same erectile dysfunction (please read the precautions on the back before filling this page), ^ τ 2 3 The resulting erection is enough to be inserted into the vagina or completely tough. Researchers believe that the transurethral effect of prostaglandin E! May be enhanced by first spreading into the corpus spongiosum and then into the corpus cavernosum. Although the above-mentioned mechanical and pharmaceutical treatments have focused on producing sufficient penile stiffness, even if the treatment can successfully produce sufficient toughness, the satisfaction of patients and their sexual partners is often insufficient. Patients are discontinued due to painful side effects, such as injectable sponges or transurethral agents. Penis implants can produce strong

200407149 l. Description of the invention () Hard, but insufficient swelling (tumescence), especially drop # γ t •, standing np farmer master (g 1 anspe η ls) insufficient swelling is recognized as the patient and his sexual relationship, 卞% Dissatisfaction Source (see U.S. Pat. No. 6, 41 8, 934; Chew & 2000) UCkey, [Content of the Invention] The present invention provides a method of medicament for patients with erectile dysfunction in two or more disease situations The treatment, which includes patients who need such treatment, places an erectile tract: an amount of semi-solid composition in the boat, which contains a vasoactive x prostaglandin and a penetration enhancer. At least one of the two or more conditions is diabetes, hypertension, heart disease, recovery from prostatectomy, or patients with erectile dysfunction who have not been treated with oral phosphodiesterase-5 inhibitors. Also ... In an ideal specific mode example, the present invention provides a method for treating patients with erectile dysfunction suffering from two or more diseases such as diabetes. In another ideal specific mode example, the present invention provides two kinds of treatment with hypertension The prescription of patients with erectile dysfunction of the above diseases = In another example of an ideal specific mode, the present invention provides a method for treating patients with erectile dysfunction of two or more diseases such as heart disease ^; another ideal specific mode next In one example, the present invention provides a method for treating patients with erectile dysfunction that recovers after prostatectomy. Furthermore, in another preferred embodiment, the present invention provides a method that does not respond to oral lipoic acid lipase-5 inhibitor therapy. Treatments for erectile dysfunction. ^ A patient is experiencing erectile dysfunction, and at the same time, at least one of the multiple disease conditions is diabetes, hypertension, heart disease, or prostasis. Recovery after adenectomy or no treatment with oral phosphodiesterase-5 inhibitors --- -14 Na scale is in use (please read the precautions on the back before filling this page) Ding Qin · The Intellectual Property Bureau of the Ministry of Economic Affairs and the Consumer Cooperatives printed the invention description (Erectile Gong nest containing a dose containing a dose of prostaglandin, One contains a multi-brewed acrylic polymer, one lipophilic group contains one C! To C to Cs aliphatic motifs (and an acidic 200,407,149 dysfunction that can be effectively treated by raising a number of semi-solid compositions in a boat shape The composition has a penetration enhancer of vascular cleanliness of about 0.05 mg to about 0.8 mg, a polymeric thickener selected from the group consisting of a polysaccharide gum and a polyacrylicacid polymer, and an ingredient ( lipophilic component) is selected from the group consisting of 8 aliphatic alcohols, a Ci aliphaticester, and mixtures thereof, and a buffer system. In a specific mode example, the vasoactive prostaglandin is prostaglandin E1; the ideal semi-solid composition is packaged in a single dosage form and the dose of prostaglandin El is about 0.05 mg to about 0.005 per single dose. 8 mg, preferably about 0.1 mg to about 0.5 mg per single dose. In addition, in a specific mode example, the dose of prostaglandin E! Is about 0.1 mg to about 0 per single dose. 3 mg. An ideal penetrat ion enhancer is an alkyl-2- (N-substituted amino) -alkanoate ester ), One (N-substituted amino) -alkanol alkanoate (N-substituted amino) -alkanol alkanoate, or a mixture of both. The buffer system provides the composition with a range of about 3 to 7.4 Buffer pH value, an ideal pH value is about 3 to about 6.5, most preferably from about 3.5 to about 6. If necessary, stabilizers, preservatives and emulsifiers can be added.奂 In specific model examples, the composition exhibits non-Newtonian rheological properties (Non-Newtonian Theological properties), suitable for including a thinning and thinning 15 paper size applicable to China National Standard (CNS) A4 specifications (210X297 mm) (Please read the precautions on the back before filling this page) Order the wisdom of the Ministry of Economic Affairs Printed by the Consumer Cooperative of the Property Bureau, 200407149 A7 B7 Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs. 5. Description of the Invention (shear-thinning) Polysaccharide gum or a thinning thin polyacrylic polymer. In one embodiment, the composition is thixotropic; in another embodiment, the composition is pseudoplastic. In an example of an ideal specific mode, the composition has a viscosity of about 5,000 centipoise (cps) to about 20,000 centipoise, and more preferably from about 7, From 0.00 centipoise to about 13,000 centipoise. An ideal pharmaceutical composition suitable for intratranavicular applications includes prostaglandin [, a penetration enhancer, a modified polysaccharide gum, a lipophilic compound, and an acidic buffer system. The permeation enhancer is selected from the group consisting of: one alkyl-2- (N-substituted amino) -alkanoate, one alkyl-2 -(N, N-bis-substituted amino) -alkanoic acid (alky 2- (N-substituted amino) -alkanoate),-(N-substituted amino) -alkanol alkanoate ((N —Substi tuted amino) -alkanol alkanoate) ---- (N, N-disubstituted amino) -alkanol alkanoates ((N, N-disubstituted amino) -alkanol alkanoate), all kinds of preparations Acceptable salts and mixtures of various groups. The lipophilic compound may be one G to C8 aliphatic alcohol and one G to ο. Aliphatic esters, or a mixture of both. If necessary, stabilizers, preservatives and emulsifiers can be added. In another embodiment, the present invention provides a composition comprising a prostaglandin El, a penetration enhancer, a cutting & thinning polymer selected from the group consisting of a polysaccharide gum and a polyacrylic polymer group, and a lipophilic compound , And one acid buffer system, --------- If C, please read the precautions on the back before filling in this page)

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This paper rule money and wealth ^ 7 ^ «) A4 size (210X297 ^ 7 200407149 V. Description of the invention (4), and the use of the mouthpiece is made for patients in two disease situations ^, obstacle drugs' patients At least one of the diseases is "illness, south blood pressure, heart disease, recovery after prostatectomy, or administration of erectile dysfunction that is not responding to phosphodiesterase-5 inhibitors. The form of administration may be semi-solid, Suitable for use in scaphoid f. If used as scaphoid drugs, these components provide effective prostaglandin penetration (_tagland 进入 enters the penis head and produces bioavailability Ui_lIability),): None,-in tissue Overloaded prostaglandin in waste: This composition further demonstrates reduced irritation to local tissues, allergies and damage. These pharmaceutical compositions are preferably packaged in a single dose adjustment. Early And further goals, objectives, designs, advantages, and similar objects, the general industry is obviously available from the scope of this month and the attached patent application according to the current technical level. ] It is known that the semi-solid prostaglandin Ει composition is suitable for the treatment of dysfunction disorder, and the composition can be used as the natural enlarged space of sin, yin and urination, namely the scaphoid fossa. A disease condition (co-morbid) refers to a disease condition presented by a patient with erectile dysfunction. The Japanese species has a pattern ΪΓΪ (f〇SSanaV1CUlariS) which provides an ideal fit :: two strong? Part 'This space is arranged with non-keratinized == epithelial cells, so it is aligned with the penile head epidermal cells and "aligned; ::: zone can be layered columnar epithelium of the urethra. ° The cell arrangement of the scaphoid fossa can therefore provide a stronger penetration than the keratinized epithelial cells of the inner and outer epidermis of the paper size ^ 200407149. * It has been found that the composition of the present invention is administered in the scaphoid fossa. It has high efficiency and low locality = good response rate. The natural enlarged cavity of Μ boat-shaped fossa is just suitable for receiving and retaining semi-solid medicaments. And the exit of this space, namely the urethra and the opening, becomes narrower. -A semi-solid medicament such as the composition of the present invention will have a relatively large fluid resistance when placed in the sun. This fluid resistance is proportional to the product of the cross-section of the channel 4 = and the length of the channel, so an appropriate choice of viscosity The solid f drug of the degree of retention naturally stays in the nest to help the absorption of the active I agent such as a blood organ dilator or the like. The viscosity of the composition ranges appropriately from about 5,000 centipoise to about 20,000 centipoise, The reason is 7,000 centipoise to about 13,000 centipoise. The heart-shaped boat-shaped fossa is part of the natural defense system, which protects the body against feelings. The boat-shaped fossa is near the cavernous body of the penile urethra. Areas more protected by the immune system Position, the placement of solid pharmaceuticals within the structural limits of the scaphoid fossa will not hinder artificially transmitted pollution such as the natural barrier to diseases caused by penile epidermis and direct access to the penile urethra. The relatively high liver sugar (glyc. (gen) content and bacterial flora provide a naturally lower pH value in the space, which can enhance the solubility of prostaglandins & in the acidic range, so the lower pH value composition can be more easily tolerated and There will be no excessive tissue irritation. 'Semi-solid compositions and penetration enhancers suitable for the practice of the present invention have been described in detail in U.S. Patent Nos. 6,040,244, 6,18, 002, and 6,323, 241, which is incorporated herein by reference. A reference to the first figure depicts the basic structure of the human penis. The scaphoid fossa 110 in the penis head 130 is a natural increase in the lumen of the male urethra. The paper size applies the Zhongguanjia standard (-(please read the precautions on the back before filling this page), * ιτ printed by the Intellectual Property Bureau of the Ministry of Economic Affairs and Consumer Cooperatives 200407149 A7-~~ -_ B7 V. Description of the invention ( ) ~ &Quot; One ^ — The large pelvic fossa extends from the distal end to the urethral opening 128 and the proximal end to the urethral drooping area 11 2 (also known as the “sponge part” area of the urethra). The urethral part passes through the penis trunk 104 (shaft). Corpus spongiosum 134 (corpus spongiosum), which is located in the middle of the pair of sponges (coorpora cavernosa) 138. The penis bulb n4 (buib hiturethra) is close to the drooping area of the urethra and passes through the sea of bulbs Cotton muscle 140 (bulbospongiosus muscle), more proximally, you can see the opening 148 in the urethral wall of the urinary globular gland (cooper's gland cowper, s glands). More proximally, the urethra passes through the prostate 160, and openings ejaculatory duct 156 and prostate utricle openings 158 can be seen on the wall of the urethra. Referring to the second figure, the structure of the scaphoid fossa n 0 inside the penis head 30 is described. The outer opening of the urethral orifice 128 is the distal limit of the scaphoid fossa, and the outer epidermis of the penis head is covered by a keratinized squamous epithelial cell 186 (pudney, j ·, an (i Anderson, DJ ·, ( 1995) Immunobiology 〇f the human penile urethra,

Amer · J · Path ·, 1 47: 1 55-1 65), the base of which is markedly transformed (dotted line) without hepatic glucose and non-keratinized squamous epithelial cells 丨 8 4, the latter is a distal scaphoid Features of litter arrangement. The Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs printed the proximal end of the scaphoid fossa widened and arranged to change into a squamous epithelial cell 182 with non-keratinized layer of glycogen, which is believed to be used to support Decreasing the pH of the area and producing a bacterial flora that is a natural defense against infection (see Holstein, AF ·, etal ·, (1991) Different epithelia in the distal human male urethra, Cell Tiss · Res · 264: 23-32). This squamous epithelial cell line with hepatic non-keratinized layer is controlled by hormones, and increases with the increase of estrogen concentration (Hoistein, __________19_ This paper standard applies to China National Standard (CNS) 8-4 specifications (210X297 Male |-200407149 A7-------- B7 V. Description of the invention () " A ~-Α · Ρ ·, et al ·, (1991)). The width of the proximal scaphoid fossa becomes narrower And are arranged in layered columnar epithelial cells 180. The semi-solid composition has a properly selected viscosity and can naturally remain in the scaphoid fossa. The semi-solid composition can exhibit Newtonian or non-Newtonian rheology In certain ideal specific examples, the semi-solid composition of the present invention exhibits non-Newtonian rheological characteristics, that is, its viscosity on the surface is determined by the shear rate of the applied composition, which is ideal. Under the circumstances, the composition has the rheological characteristics of "shear thinning". The "shear thinning" referred to here refers to the decrease of the external viscosity with the increase of the shear rate (the shear stress and the shear rate Ratio), regardless of the appearance viscosity is independent of time ( Pseudoplastic), time-dependent (thixotropic), or stress-related, which is defined as a stress that must be exceeded before the fluid begins (Bingham Plastics and Generalized Bingham Plastics); usually refer to Harris , J., & Wilki nson, WL, "Non-newtonian Fluid," pp.856-858 in Parker, S.P.ed., McGraw-Hill Encyclopedia of Physics, Second

Edition, McGraw-Hi 11, New York, 1 993. A suitable composition has a viscosity ranging from about 5,000 centipoise to about 20,000 centipoise. The more desirable is from about 7,000 centipoise to about 13,000 centipoise. In a preferred embodiment, the pharmaceutical composition includes at least one vasoactive prostaglandin, ideally prostaglandin Ei; an alkyl (N, N-disubstituted amino) ester; a polysaccharide gum; a lipophilic compound and an Acidic buffer system. Prostaglandins can be dissolved or uniformly dispersed in a topical composition, preferably soluble (and soluble) in a topical composition. Vasoactive prostaglandins function as peripheral vasodilators, including naturally occurring prostaglandins such as PGEi, PGAi, PGBi, PGFla, _ ..__ 20 This paper is suitable for National Standards (CNS) of China (210X297) 11 '' (Please read the notes on the back of the page before filling out this page)-Order-Printed by the Employees' Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs, 200407149 A7 B7 V. Description of the invention () 19 Hydroxylated-PGAi, 19 Hydroxy-PGB !, PGE2, PGA2, PGB2, 19-hydroxyl-PGA2, 19-hydroxyl-PGB2, PGE3, PGF3a; semi-synthetic or synthetic derivatives of natural prostaglandins include carboprst ΐromethamine, dinoprost tromethamine 'dinoprostone, lipoprost, gemeprost, metenoprost, sulprostne and tiaprost Prostaglandin E! And prostaglandin E2 are particularly desirable vasoactive prostaglandins for use with the methods of the present invention. The amount of vasoactive prostaglandins in the pharmaceutical composition of the present invention, such as prostaglandin Eι, is a curative effect (also (I.e., an erection), and change as needed: for example, according to the specific vasoactive prostaglandin to be delivered, to be treated Indications, skin surface area and the formulation of the mucosa, other ingredients of the composition, the desired dose, dosage form (ie suppository or topical), and the use of special forms of vasoactive prostaglandins. The term "prostaglandin" is here Used under the scientific name, it refers to prostaglandin free acid and pharmacologically acceptable derivatives, including prostaglandin E! (PGEi), pharmacologically acceptable salts, and low-value alkyl esters (as used in this The term "low-value alkyl" means a straight or branched chain alkyl group containing one to four carbon atoms). The composition usually contains, based on the total weight of the composition, about 0.001 to 1 weight percent Prostaglandin E! Is typically about 0.05 to 1 weight percent of prostaglandin Ei, and is desirably about 0.1 to 0.5 weight percent. In a specific mode example, the composition The amount of prostaglandin E! In the composition is about 0.07 to 0.4% by weight based on the total weight of the composition. Prostaglandin E! Is well known to those skilled in the industry today, so it is listed The ideal number is not practical, but it will familiarize the industry —— 21 _ This paper size applies to China National Standard (CNS) A4 specification (210X297 mm) I -------- lpf (Please read first Note on the back, please fill out this page again.) Order-Printed by the Consumers Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs, 200407149 Invention Description (It is easy to order after properly considering the aforementioned factors. References to its pharmacological effects, side effects, and normal dosage range can be found in different literatures, such as Physician, s Desk

Reference, 51st Ed. (1 997); The Merck Index, 12th

Ed., Merck & Co., N.J. (1996); and Martindale The

Extrapharmacopoeia, 28th Ed., London, The Pharmaceutical Press (1982). In addition, simultaneous administration of one or more non-ecosanoid vasodilators is to be expected, and in some cases it has been shown Additive effect, and use praz0sin and prostaglandin E! Found to be particularly advantageous at this point, the latter showed a strong effect of prazosin. Suitable non-ecosanoid vasodilators include ( (But not limited to this): nitrates such as nitroglycerin, i sosorbide dinitrate, erythri ty 1 tetrani trate, nitrous acid Amy 1 nitrate, sodium nitroprusside, molsidomine, linsidomine chlorhydrate (SIN-1), and S-nitroso-N-acetyl- d, 1 -penicillamine ("SNAP"); amino acid (81111 丨 110 & (: 丨 (1), such as 1-arginine ([-& ^ 丨 11 丨 116); long-acting and short-acting 曱 type A-adrenergi c blocker, for example Such as phenoxybenzamine, dibenamine, phentollamine, tamsulosin, and indor amine, and J is a quinazoline derivative such as alfuzosin, bunazosin, doxazocin, terazosin, prazosin, and trimazosin; 22 M's scale is applicable to the Chinese National Standard (CNS) A4 specification (210X297 (Mm) ---------— i! (Please read the notes on the back before filling out this page),-= 'Printed by the Consumers ’Cooperative of Intellectual Property Bureau of the Ministry of Economy and Economics 200407149 A7 B7 V. Invention Explanation () Natural herbal composition with vasodilating properties and its bioactive extracts, such as gosyajinki-gan, Satureja obovata, bai-hua qian-hu, (Please read the precautions on the back before filling this page) Economy Printed by the Consumer Cooperatives of the Ministry of Intellectual Property Bureau, 1ipotab, saiboku-to, vinpocetine, Gingko biloba, bacopa, Gynostemma pentaphvllum, gypenosides, Evodia rutaecarpa, rutaecarp i ne, dehydroevod i am i ne, dan-shen, sa1v ie mie shosaikoto, Zizyphi fructus, mixtures of ginseng and above (US Patent 6,007, 824); Ergotine ( ergot alkaloids), such as ergotamine and ergotamine analogs, that is, acetergamine, brazergo1ine, bromerguride, cianergo1ine, delorgotrile, disulergine, ergonovine maleate, ergonovine maleate Ergotamine tartrate, etisulergine, lergotrile, lysergide, mesulergine, metergo line 'metergotam i ne' nicergoline 'pergolide, propisergide, proterguride and terguride; antihypertensive agents j such as diazoxide, hydralazine and Vasodilators such as nimodepine, pinacidil, cyclandelate, dipyridamole, and isoxsuprine; chi orpromazine; haloperidol; yohimbine, trazodone, and vasoactive intestinal peptides ° One trip Piperazinyl quinazoline antihypertensive agents such as prazosin, when used in combination with a vasoactive prostaglandin, the amount is about 0.1 mg to about 2.0 mg per unit dose, The effectiveness and intensity of each specific piperazine hawazoline antihypertensive agent is based on the following standard: ~ ____: _____ 23 ____ ____ This paper size applies to the Chinese National Standard (CNS) A4 specification (210 X 297 mm) A7 200407149 _B7_ V. Description of the invention ( ) And the type and dosage of vasoactive prostaglandin used. The doses and ratios of vasoactive prostate and piperazine oxazoline antihypertensive agents can be routinely determined by those skilled in the art. The topical composition may include one or more penetration enhancers. The ideal penetration enhancers of the present invention are ethanol, propylene glycol, glycerol, and ethyl laurate. , Isopropyl palmitate, isopropyl myristate, laurocapram (AzoneTM), dioxolanes (described in US Patent No. 4,861,764), macrocyclic ketones (macrocyclic ketones), HP-101, oxazo 1 idones, and biodegradable penetration enhancers (described in US Patent Nos. 4, 980, 378, and 5, 082 to Wong et al. U.S. Patent No. 6,118,020 to Btiyiiktimkin et al, such as alkyl-2- (N-substituted amino) alkanoates, alkyl-2- (N Alkyl-2- (N, N-disubstituted amino) alkanoates), that is, dodecyl N, N-dimethylamino isopropylate (dodecyl N, N- dimethylamino isoproprionate (DDAIP)), N-substituted amino alkanol al kanoates), N, N-disubstituted amino alkanol alkanoates, and acid addition salts and mixtures thereof. For example, the crystals of DDAIP contain acid salts DDAIP and an optional group of acids are cooled and mixed in a water-immiscible solvent such as hexane, which is described in U.S. Patent No. 6,118,020, the contents of which are incorporated herein by reference. Dodecyl 2- (N, N-dimethylamino) -propionate (DDAIP)) can contain inorganic or organic, representative inorganic acids Salts include hydrochloric, hydrobromic, suifuric, phosphate, nitrate-containing acid salts and solvates of DDAIP. Examples of acid-containing salts of organic acids include acetic, benzoic, and water. ___24__ This ^^ standard is suitable for financial and family protection (〇 ^) "4 secrets (21 () \ 297 mm ) '~----------— i., (Please read the notes on the back before filling this page)

Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs of the 1T line 200407149 A7 B7 V. Description of the invention () ~~ ^ * (Please read the precautions on the back before filling this page) Acid (salicylic), glycolic acid (giyC〇uic ), Succinic, nicotinic, tartaric, maieic, mauc, palmoic, m'ethanesulfonic, The acid-containing salts of cyclohexanesulfamic acid, picric acid, and lactic acid, and their individual solvates. Among these inorganic acid salts are DDAIP hydrochloride and DDAIP sulfate. The amount of penetration enhancer must be sufficient to enhance the penetration of prostaglandin E, and the specific amount must depend on the desired release rate and special form of prostaglandin Ei. Generally, the amount of penetration enhancer is in the composition The total weight is based on about 0.5 weight percent to 20 weight percent. Ideally, the amount of the penetration enhancer ranges from about 1 weight percent to 10 weight percent of the composition; more preferably, the amount of the penetration enhancer ranges from about 1 weight percent to 5 of the composition. Weight percent. Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs. Generally, suitable penetration enhancers can be selected from the groups listed above, such as sulfoxides, alcohols, fatty acids, fatty acid esters (Fatty acid esters), polyols, amides, surfactants, terpenes, alkanones, organic acids, and mixtures thereof . Generally refer to the Penetration Enhancer Classification of Chattaraj, S.C. and Walker, RB, page 5-20 in Maibach, R.I., and Smith, R.E., (eds.), Percutaneous Penetration Enhancers, CRC Press, Inc .; Boca Raton, FL (1995) and Biyyiiktimkin, N., et al., Chemical Means of Transdermal Drug Permeation Enhancement, in Gosh, TK, et al., (Eds.) Transdermal and Topical Drug Delivery Systems, Interpharm Press, Inc., Buffalo Grove, IL (1997). Appropriate sub-types include dimethylsulfoxide, decylmethylsulfoxide _ ._25 This paper is compliant with the Chinese National Standard (€ milk) 8 4 (210 '/ 297 mm) ) 200407149 Description of the invention (and mixtures thereof. Suitable alcohols include ethanol, propanol, butanol, pentanol, pentanol, hexanol, octanol (Octanol), nonanol, decanoi, 2-butanol, 2-pentanol, benzyl alcohol, capry lie alcohol), decyl alcohol, iauryi aic〇h〇i, 2-iauryi alcohol, myristyl alcohol, cetyl alcohol, Stearyl alcohol (oleylic alcohol), linoleic alcohol (linoleic alcohol), linoleic alcohol (linoleic alcohol) and mixtures thereof. Suitable fatty alcohols夂 includes valeric, heptanoic, pelargonic, caproic, capric, laurel (Lauric), myristic, stearic, oleic nnoleic, linolenic, caprylic, isovaleric, isovaleric, Neopentanoic, neoheptanoic, neononanoic, trimethyl hexanoic, neocanoic and isostearic acids and mixtures thereof Suitable fatty acid species include isopropyl n-butyrate, isopropyl n-hexanoate, isopropyl n-decanoate, meat Isopropyl myristate, isopropyl palmitate, octyldodecyl myristate, ethyl acetate, butyl acetate acetate, methyl acetate, methylvalerate, methylpropionate, diethyl sebacate, ethyl oleate, stearin Ethyl laurate and mixtures thereof. Suitable polyols include propylene glycol, polyethylene glycol, polyethylene glycol, ethylene glycol, diethylene glycol, trie * thylene glycol, Dipropylene glycol, glycerol, propanediol, sorbitol, glucose 26 This paper is sized to the Chinese National Standard (CNS) A4 (210X 297 mm) (please first Read the notes on the back and fill in this page)-Order printed by the Intellectual Property Bureau of the Ministry of Economic Affairs, Consumer Cooperatives, 200207149 A7 B7 V. Description of the invention () dextrans, butanediol, pentanediol , Hexanetriol and mixtures thereof. Suitable amides include urea, dimethylacetamide, diethyltoluamide, dimethylformamide, dimethyloctamide ), Dimethyldecamide, 1-alkyl-4-imidazolin-2-one, pyrrolidone derivatives, Cyclic amides, hexamethylenelauramide and its derivatives, diethanolamine, trie * thanolamine, and mixtures thereof. Suitable pyrrol idone derivatives include 1-methyl-2-pyrrolidone, 2-pyrrolidone, 1- Lauryl-2-pyrrolidone (1-lauryl-2-pyrrolidone), 1-fluorenyl-4-weilyl-2-opyrrolidone (1-11161: 1 ^ 1-4-〇81 * 1) 〇7-7-2-07] ^ 〇11 (1〇116), 1-hexyl-4-tyryl-2-σbirozolium (1-hexyl-4-carboxy-2-pyrrolidone), 1-lauryl-4-carboxy-2-pyrrolidone (1-lauryl-4-carboxy-2-pyrrolidone), 1-decyl-thioethyl-2- ° each -2-pyrrolidone (HP-101)), 1-methyl-4-methoxycarbonyl-2-pyrrolidone (1-methyl-4-methoxycarbonyl-2-pyrrolidone), 1-hexyl-4-methoxycarbanyl 2-hexyl-4-methoxycarbonyl-2-pyrrolidone, 1-lauryl-4-methoxycarbonyl-2-pyrrolidone. (1 -1 aury 1 -4-methoxycarbony 1 -2-pyrro 1 i done), N-cyclohexyl-pyrrolidone (+ 10〇 (: 10116 乂 乂 10 乂) ^ 〇11 (1〇116), 1 dimethylaminopropyl ° Biloxazone (N-di methyl ami nopropyl pyrrol i done), N-cocoalkypyr roli done, N-tallowalkypyrrol idone, N- (2-Ethylamino) -2- ° specific ketones • (N- (2-hydroxymethyl) -2-pyrrolidone) fatty acid esters and their mixtures. 27 Applicable to Chinese countries as far as possible Standard (CNS) A4 specification (210X297 mm) (Please read the notes on the back before filling out this page) Order Qin · Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs, 200407149 A7, Invention Description (I ------ --- (Please read the notes on the back before filling this page} Suitable cyclic amidines include 1-dodecylazacycloheptane-2-one (1-dodecylazacycloheptane-2-one (laurocapram, AzoneTM )), L-'geranylazacycloheptan-2-one, 1-farnesylazacycloheptan-2-one 1-geranylgeranylazaheptan-2-one (1-geranylgeranylazacycloheptan-2-one), 1- (3, 7-dimethyloctyl) azacycloheptane-2 -Ketone (1- (3,7-(^ 11 ^ 1: 1 ^ 1〇 (^ 乂 1) 32 & 〇7 (: 1〇1 ^ 0 ± & 11-2-〇116), 1- ( 3,7,11-trimethyloctyl) azacycloheptan-2-one (1- (3, 7,11-trimethyloctyl) azacycloheptan-2-〇ne), l- Geranylazacyclohexane-2-one, 1-geranylazacyclohexane-2-one, 1-geranylazacyclohexane-2-one (1 -geranylazacyclopentan-2, 5-dione), 1-farnesylazacyclopentan-2,5-dione (l-farnesylazacyclopentan-2-one), and mixtures thereof. Suitable surfactants include anionic surfactants (anionic surfactants), cationic surfactants, nonionic surfactants, bile salts and eggs Lecithin. Suitable anionic surfactants include sodium laurate, sodium lauryl sulfate, printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs, and mixtures thereof. Suitable cationic surfactants are cetyltrimethylammonium bromide, tetradecyltrimethylammonium bromide, benzalkonium chloride, octadecyltrimethylammonium chloride, decyl Cetylpyridinium chloride, dodecyltrimethylammonium chloride, hexadecyltrimethylammonium chloride, and mixtures thereof. Suitable non-ionic, sub-surfactants include alpha-hydrogen-omega-hydroxy-poly (ethylene oxide) -poly (propylene oxide)

200407149 Printed by A7 B7, Consumer Cooperative of Intellectual Property Bureau of the Ministry of Economic Affairs 5. Description of the Invention (a) Hydro-co-hydroxy-po 1 y (oxyethy 1 ene) -po 1 y (oxypropy 1) po 1 y (oxyethy 1 ene) b 1 ock copolymers), polyoxyethylene ethers, polyoxyethylene sorbitan esters, polyethylene glycols of fatty alcohols Polyethylene glycol esters of fatty alcohols and mixtures thereof. Suitable a-hydrogenated-co-hydroxy-poly (ethylene oxide) -poly (propylene oxide) poly (ethylene oxide) block copolymers include Poloxamers 231, 182, and 184 and mixtures thereof. Suitable polyethylene oxide scales include 4-lauryl ether (4-lauryl ether; (BRIJ 30 ™), (BRIJ 93 ™), (BRIJ 96TM)), 20-oleyl ether (20-oleyl

ether; (BRIJ 99 ™)) and mixtures thereof. Suitable polyoxyethylene sorbitan esters include the monolaurate (TWEEN 20TM, SPAN 20 ™), the monopalmitate (TWEEN 40TM)), the monostearate (the monostearate; (TWEEN 60TM)), and the monooleate (TWEEN 80 ™)) and mixtures thereof. Suitable polyethylene glycol esters of fatty alcohols include 8-oxyethylene stearate ester; (MYRJ 45TM), (MYRJ 51 ™)), 40-ethylene oxide stearate (40- oxyethylene stearate ester; (MYRJ 52 ™)) and mixtures thereof. Suitable bile salts include sodium cholate, laurocholic acid, sodium salts of laurocholic, glycolic and desoxycholic acids, and mixtures thereof. Suitable terpenes include D-limonene, a-pinene, β-enrene, a-terpine〇i , Terpinn-4-ol, d-carvol, carvol, carvone, pulegone, pepperone, menthone , / Menthol, geraniol, CyCiOhexene oxide, limonene oxide, α-pinene oxide, oxidized ring Cyclopentene oxide, 1,8-eucalyptol (i, 8-cineole), ylangylangoi 1, aniseoil, chenopodiumoil, 29 paper paper scale applicable to China National Standard (CNS) A4 specification (21 ox 297 mm) ---------- φ !, (Please read the precautions on the back before filling this page) Thread one 200407149 A7 ----- ---- B7 V. Description of the invention () ^ 1— ~ Eucalyptusoil and its mixture. Suitable alkanones include N-heptane, N-octane, N-nonane, N-decane, and n-decane (N-undecane), N-dodecane, N-tridecane, N-tetradecane, N-hexadecane and mixtures thereof. Bai Shi's organic mash includes citric acid, succinic acid, salicylic acid, saiiCyiates [including methyl, ethyl and propyl glycol Derivatives], tartaric acid and mixtures thereof. Natural and artificial semisynthetic polysaccharide gums are also an important component of the composition ' suitable representation; gums are among these species. A galactose mannan polysaccharide (ga 1 actomannan gum) is a carbohydrate polymer containing D-galactose and D-mannose units or derivatives of such polymers. There are many types of galactomannans, the composition of which is different depending on the origin of the galactomannan. The characteristic of galactomannan T is a β-D-mannose ° β-mannopyranosy 1 unit. (1- > 4) Connected linear structure 'single aD-mannopyranosyl (α-D-manopyranosy 1 :) Unit (1 ~> 6) is connected to the main chain and is a branch thereof. Galactomannan gum includes guar gum, which is an inner layer of two leguminous plants (Cyamposis tetragonalobus and psoraloids) ground into powder, and the other is carob gum ( locust bean gum), which is found in the endoderm of carobtree seeds. Suitable artificial semi-synthetic polysaccharide gums include natural or gastric-replacement * polysaccharide gums, such as carboxymethy 1 30 paper Standards apply Chinese National Standard (CNS) A4 specifications (210 x 297 mm) (Please read the precautions on the back before filling this page)

Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs of the Ministry of Economic Affairs of the People's Republic of China, 200407149 A7 B7 V. Description of the invention () ethers), ethylene glycol ethers, and propylene glycol (pr〇pylene giyC〇i ethers) ). An example of an alternative polysaccharide gum is methyl cellulose (methy lcel lulose), an ideal artificial galactose galactose gum is guar gum. Other suitable representative gums are agar gum, carrageenari gUm, ghatti gum, karaya gum, rhamsan gum, and Xanthan gum. The composition of the invention may contain a mixture of different gums, or a mixture of gums and acidic polymers. Gum, in particular galactomannan gum is a well-known raw material 'Reference Example' Industrial Gum: 4 Their Derivatives, Whistler RL and BeMiller JN · (eds ·), 3rd Ed · Academic Press (1992), and Davidson RL, Handbook of ¥ ater-Soluble Gums & Ae, ?? /? $, McGraw-Hill, Inc., NR (1 980). Most of the gums are available in different types in the market, usually in powder form, and can be used for food and local composition immediately. For example, powdered carob gum can be obtained from (661〇3111, elbow 0) company. Based on the total weight of the composition, the amount of polysaccharide gum in the composition, which ranges from about 0.1% to 5%, more preferably The range is from 0.5% to 3%. In a specific model, the amount of polysaccharide gum is 2.5 weight percent. The composition described in detail is exemplified below. The selected alternative is polyacrylic acid poly31. The paper size is applicable to the Chinese National Standard (CNS) A4 specification (210 X 297 mm) (Please read the precautions on the back before filling this page) -5-t > b Ministry of Economy Wisdom Printed by the Consumer Cooperative of the Property Bureau, 200407149 A7 B7 V. Description of the Invention Polyacrylic acid polymer, a common polyacrylic acid polymer is commonly known as "polycarb" ("carbomeru"), Polyacrylic acid Polymers and polyalkenyl polyether polymers are loosely cross-linked. Products are available from the B. Goodrich Company (Akron, Ohio) under the trade name " carb〇p〇ltm „, A special variant of polycarbonyl is called“ carbopol 940 ”. Other suitable polyacrylic acid polymers are available in the market. The trade name is“ Pemulen ™ '1 (B · F Goodrich

Company) and " P0LYCARB0PHILTMn (Α · Η · Robbins,

Richmond, VA). Pemulen ™ polymers are poiymers are copolymers of C1G to C3o aikyl acrylates and one or more monomers such as acrylic acid, methacrylic acid or one of their simple esters, the latter being loosely cross-linked to One aiyi ether of sucrose or any 1 ether of pentaerythritol. The POLYCARBOPH ILTM reinforcement is a polypropylene glycol cross-linked butadiene glycol. The amount of polyacrylic acid polymer in the composition ranges from about 0.5 percent to 5 percent by weight based on the total weight of the composition. Another important ingredient is the lipophilic (1 i poph i 1 i c) ingredient. The "lipophilic ingredient" as used herein refers to a pharmaceutical that is both lipophilic and hydrophilic (hydrophi 1 ic). Those of ordinary skill in the pharmaceutical industry today can understand the nature of lipophilicity, or the "lipophilic property" (1 i poph i 1 ici ty) of a specific compound. The usual quantitative method is to use the partition coefficient (part it ion coefficient) ) And other compounds 32 Winter paper size applies Chinese National Standards (CNS) M specifications (21〇 > < 297mm) (Please read the precautions on the back before filling this page)

'IT% Printed by the Intellectual Property Bureau of the Ministry of Economic Affairs' Consumer Cooperatives 200407149 A7 B7 V. Description of Invention () Comparison 'The distribution coefficient is defined by the International Union of Pure and Applied Chemistry (I UPAC)' , Refers to the proportion of a substance distributed in the two phases when the (two-phase) heterogeneous system reaches equilibrium; the ratio of the concentration of the same molecular species (or directly called activity) in the two phases is constant at a fixed temperature.

The Ci to Cs aliphatic alcohols, C2 to C30 aliphatic esters and mixtures thereof can be used as lipophilic ingredients. Suitable exemplified alcohols are ethanol, n-propanol and isopropanol and suitable esters are ethyl acetate, butyl acetate, lauric acid Ethyl laurate, methyl propionate, isopropyl myri state, and isopropyl pa Imitate. The aliphatic alcohols referred to herein include polyols such as glycerol, propylene glycol, and polyethylene glycols. In a specific mode example, a mixture of alcohols and esters is desirable, and a mixture of ethanol and ethyl laurate is particularly desirable. In a specific mode example, C2 to C3 included in the lipophilic component. Aliphatic esters include C8 to C30 glycerol. Fatty esters of glycerol are selected from the group consisting of: monoglycerides S (m ο η 〇g 1 ycerides), diglycerides, triglycerides g triglycerides) and mixtures thereof. Suitable aliphatic esters include saturated fatty acids, glycol esters of unsaturated fatty acids, and mixtures thereof. Appropriate saturated fatty acids include caproic acid 33 This paper is sized for China National Standard (CNS) A4 (21 0 x μ7 male diamond) (Please read the precautions on the back before filling this page)

, 1T printed by the Consumer Cooperative of Intellectual Property Bureau of the Ministry of Economic Affairs, 200407149 printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs, printed A7. capric acid), lauricacid, myris1; ic acid, palmitic acid, stearic acid, arachidicacid, behenic acid And lignoceric acid; suitable unsaturated fatty acids include oleic acid (〇1 eic ac id), linoleic acid (1 丨 no1 eic acid) and linolenic acid (1 in〇ienic acid); suitable Glycol vinegars include glyceryl monooleate, triolein, trimyristin, and tri stearin. Cardamom oil. The concentration of the necessary lipophilic ingredients varies with other factors, such as the semi-solid consistency to be achieved (con s i s t en c y) and the skin penetration boost to be achieved. A suitable concentration of lipophilic ingredients is based on the total weight of the composition and ranges from 0.5% to 40% by weight. The range of ideal lipophilic ingredients for topical compositions is based on the total weight of the composition. In the range of 7% to 40% by weight. When a mixture of aliphatic alcohols and aliphatic esters is used, the appropriate amount of alcohol is from 0.5% to 10%. In an ideal embodiment, the number of 'alcohols is 5% to 15%, and the number of aliphatic esters is 2% to 15% (again, based on the total weight of the composition). In another preferred embodiment, the number of alcohols is 0.5% to 10%, and the number of aliphatic esters is 0% to 10% (again, based on the total weight of the composition). An optional, but better, ingredient is an emulsifier (emu; si fier). Although not a key factor, a suitable emulsifier will usually exhibit a hydrophilic-lipophilic: equilibrium number greater than 10. Sucrose esters, especially sucrose stearate (sucr〇se This paper size is applicable to China ^ standard (-~~ (Please read the precautions on the back before filling this page)

200407149 Printed A7 by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs Agent, sucrose stearate is a well-known emulsifier and is available from various commercial sources. When used as an emulsifier, the amount of sucrose stearate (based on the total weight of the composition) is ideal, and the ideal amount of sucrose emulsifier can also be based on the weight of the emulsifier and polysaccharide tree = for example It shows that an ideal ratio is 1: 1 to 6 emulsifier to gum, and it is the most ideal to produce the desired semi-solid consistency and separation resistance (separatiónresistance). Other emulsifiers also suitable for use include polyoxyethylene sorbitan esters; long chain alcohols, ideally cetostearyl alcohol and fatty acid glycerides ( fatty acid glycerides). Suitable polyoxyethylene sorbitan esters include flaunolaurate W Tween 20tm, span 20TM, monopalmiate such as Tween 40TM; monostearate Monostearate such as Tween 60TM; and monooleate such as Tween 80TM and mixtures thereof. Ideally, the fatty acid glycerol g purpose includes glycerol monooleate g purpose (g 1 y c e r y 1 monooleate), triolein, trimyristin, and tristearin. The composition includes an acid buffer system (ac i d bu f f er system). The pH value of the acid buffer system as a maintenance or buffer composition is within a desired range. As used herein, the term "buffering system" or "buffering" refers to a solute agent (s ο 1 ute) or multiple solute agents. When stored in a solution, it can stabilize the solution when adding acid or alkali to the solution. To resist major changes in the pH value (or the activity or activity of hydrogen ions), these solutes begin to buffer the pH value within the above range to resist -—— ___—_ 35 _ This paper size applies to national standards ( CNS) M specification (2 丨 〇 < 297 male thin) (Please read the precautions on the back before filling out this page) I-· Order · 200407149 A7 B7 V. Description of the invention () Changes in acid test value, This is well known. Although suitable buffers are not countable, potassium phosphate monohydrate has proven effective in the compositions of the present invention. The final pH value of the pharmaceutical composition may change within the physiologically compatible range, but it must be that the final pH value is non-irritating to human skin. Without violating this restriction, you can choose a pH value to improve the stability of prostaglandin E1 and adjust the consistency if necessary. In a specific mode example, the ideal pH value is about 3 to about 7.4, more preferably about 3 to about 6.5, and most preferably about 3.5 to about 6. The remaining component of the composition is water and must be purified (pUr ifie (j). The water content of the composition is about 50% to about 90%, based on the total weight of the composition. The content of water in the water is not special; Critical, however, can be adjusted to achieve the desired consistency and / or concentration of other ingredients. Prostaglandin E! Stabilizers, colorants, rheological agents, and preservatives can be added to an extent that does not unduly limit the skin permeability of prostaglandin El Or prevent the desired solid consistency. Semi-solid pharmaceutical compositions are expected to be in the form of creams, gels, ointments, colloidal suspensions, and the like The composition also includes the following but is not limited to suitable composition use, and there are transdermal patches and similar devices. The components listed above can be combined in any order or manner, so as to produce a stable composition including a Prostaglandin Eι is a semi-solid formulation with a uniform distribution. One useful method for preparing such compositions includes uniformly spreading a polysaccharide gum (or polyacrylic acid polymer) in one, in advance Mixed in water / buffer solution, and then thoroughly homogenized 36 This paper size applies Chinese National Standard (CNS) A4 regulations f Ή Ω? Q7 eight (please read the precautions on the back before filling this page) Order the Ministry of Economic Affairs Printed by the Intellectual Property Bureau Staff Consumer Cooperatives 200407149

Printed by the Consumer Affairs Co., Ltd. of the Intellectual Property Agency of the Ministry of Economic Affairs, ^ ⑽〇genizing), that is, mixing the final mixture, i.e. 丨 丨. In the presence of emulsifier, add A before adding water / buffer solution. Two ::::::: Any suitable method can be used, such as adding == On the other hand, prostaglandin El is dissolved in the portion by stirring. The latter may be an alcohol. . Second, add a penetration enhancer. The right lipophilic ingredients of one or two include an alcohol and an ester. Di-prostaglandin El can dissolve in the osmotic enhancer first: in vinegar. In these two methods, it is finally mixed with m: ". The final step is to slowly (ie, dropwise :::, and continue mixing. ^ Results of topical conjugates, when compared, show the aforementioned benefits including improved prostaglandin Eι permeability and living body Usability and…, overloading of music; reduced skin damage and related inflammation 丨 elasticity designed in the form of strength. These components can be used for long-term treatment of border vessel disease, male yang and other prostaglandins Disorders of El treatment, which can avoid the low bioavailability and rapid chemical decomposition of other methods of administration. Applying prostaglandin El to the skin of a patient with a topical composition makes a predetermined prostaglandin The amount of El can be continuously injected into the disease ^ and avoid the adverse effects of one-time or multiple injections into larger doses. By maintaining a continuous dose rate, prostaglandin E, the patient The concentration of the target tissue can be better maintained within the ideal treatment range. C Please read the precautions on the back before filling this page)

、 1T Qin · I-II I .....- 37 This paper size applies to Chinese National Standard (CNS) A4 (210X 297 mm) 200407149 Μ B7 V. Description of the invention () In a specific model example, one The composition contains about 0.001% to about 5% modified polysaccharide gum; about 0.01% to about 1% of prostaglandins, selected from the group consisting of prostaglandin E !, Pharmacologically acceptable salts, their lower carbon number alkyl esters, and mixtures thereof; about 0.5 to about 10% of DDA IP or its salts; about 0.5 to about 10% Lower carbon number alcohols' are selected from the group consisting of ethanol, propanol, isopropanol, and mixtures thereof; from about 0.5% to about 10% of esters are selected from the group consisting of lauric acid Ethyl ester, isopropyl myristate, isopropyl laurate, and mixtures thereof; based on the weight of the composition, and an acid buffer. Preferably, the composition also contains about 2% of sucrose gallate. The composition may optionally also contain up to about 5% of an emulsifier. Ideally, the composition may also contain up to about 2% of an emulsifier. Suitable emulsifiers include polysorbates such as Tweens, glyceryl rnonooleate, triolein, trimyristin, and tr is tear in. The ideal emulsifier is trisomycin . Printed by the Employees' Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs Please read the notes on the back before filling out this page} The practical application of the present invention will be demonstrated in the following examples. The significance of these examples is to describe the present invention rather than limit its scope. Changes in the therapeutic composition that do not adversely affect the effect of prostaglandin E! Will be shown to the state of the art today and are within the scope of the present invention. For example, added ingredients such as coloring agents, antimicrobial preservatives, emulsifiers, fragrances, prostaglandin El stabilizers, and the like can be included in the composition, as long as the final result is as described above. Nature. When these ingredients are present, preservatives are usually added from about 0.05% to about 0.30%. Suitable preservatives include methyl paper. The paper is sized to the Chinese National Standard (CNS) 8-4 (21〇X). 29? Public envy) 200407149 Λ7 Α7 Β7 V. Description of the invention () Parabens (methy 1 parabens; methy 1 PABA), propylparabens (propylparabens; propyl PABA), and butylhydroxy toluene; BHT). Suitable perfumes and fragrances are well known in the industry; a suitable fragrance is up to 5% myrtenol, ideally about 2% myrtenol, based on the composition Based on total weight. The composition of the present invention also includes a small amount of a local anesthetic, if necessary, from about Q · Q 1 to about 4% by weight. Typical local anesthetics include lidocaine, dyclonine, dibucaine, their pharmaceutically acceptable salts, and mixtures thereof. In a specific mode example, the local anesthetic is about 0.5% dyclonine, based on the total weight of the composition. The dosage formulation is preferably made in a single 1-dose form (unitd. Zero 2 ', so that the formulation can be subdivided into several containing the appropriate amount of active ^, earlier doses (unit doses). Single-dose dosage forms are rigid wings ： L; 、 Paris's plastic knife dispenser (packet) or (packet) of the pharmaceutical preparation. \ 疋 Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economy (Fill in this page again.) Another aspect of the present invention is a manufacturing process. Group c is used to treat erectile dysfunction, as described above. It is in a suitable container, ideally in a container. Combination: Dispenser No. 6,223,573, and; in the United States, for example, a tube with an extended tip, -m -ϋ In f, suitable for opening size, or a squeeze bottle, and any suitable plastic Or elastic plastic. Manufactured from materials such as 39 [standards apply to Chinese National Standard (CNS) A4 specifications (21〇 > < 297 printed by the Intellectual Property Bureau of the Ministry of Economic Affairs, Intellectual Property Bureau, staff consumer cooperatives) 200407149 V. Description of the invention ( Iron usage The form can be a pamphlet and a wrapping paper for labeling. The labeling and usage instructions for items made by men and men are provided to provide the penis of a patient who has prematurely impaired the composition of the present invention. # ” The method of working up the stem to make the urethral opening 'instruct the patient to hold the yin and extend the tip of the container into the opening, ^ do not administer it in the den-like nest, see Figure 3A to 3, Gang Zai 5 and 5 To 30 minutes, it shows the picture of the private person B on the function. The printed label usage refers to the description and description. Two! Class iron usage barriers. Proven in the composition; .2 by the competent national authority

AdminiStrati〇n) Approved ni = Cao F〇〇d and Dr. An accompanying mang deduction barnyard: City of L. Part of the process includes providing a label for a group of two or two music composition, although the label includes the transfer: 筚 物 二 Ϊ Ϊ other content such as pharmacological action, action mechanism, total fungality, pharmacokinetics , Absorption, bioavailability, ^ usage. Two similar, it also provides the necessary dosage, administration method ^ ^, once the drug is marketed to the patient, the composition is combined with a knife match and just notice * Zhan, human & — ^ ^ field treatment The deduction is very important for the correct use of the drug. Therefore, the 2nd 4t method is used to describe its use. It should not be treated according to the treatment described here. The active ingredients contained in the formulation The amount can change or regulate the application and intensity of vasoactive prostaglandins, adenine is prostate Λ. For example, for example, the vasoactive forefront U5 mg to / 8 milligrams. Mother = the amount of prostaglandin El in one dose is about υ · δ pen grams, more preferably about 0.1 mg to 0.5 China (CNsTm ^ (21〇X297 ^ t) (Please read the notes on the back before filling this page)

200407149 V. Description of the invention (in a specific model example, each single dose contains about 0.1 grams. If necessary, the composition can also include other on-line treatments such as piperazinyi, half Solid vascular compositions should be applied 2 to 30 minutes before sexual intercourse 'preferably 5 to 15 minutes before sexual intercourse. Some examples of such models that can engage in a treatment that does not need to be associated with pre-intercourse' are semi-solid Vasoactive prosthetics are applied in the scaphoid fossa of the penis at least once every other day every other week, or every day, as indicated by each other. Each composition can be prepared by mixing the ingredients together according to traditional methods.

Example 1: Topical Prostaglandin El Composition A Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs, milligrams, milligrams to compatible anti-T% blood on the body model therapy of active pre-penis, the most effective Place individual and another 0.3 milligrams of therapeutic agent. In the case of "See the stagnation of the stagnation hormone of staglandin, the method is good and the instructions are different (please read the precautions on the back before filling this page). Composition A is prepared as follows. A part of the composition is as follows: Dissolve 0.4 parts by weight (by we i ght) of alprostadi Eila (Alprostadi 1 USP) in 5 parts by weight of ethanol ( ethyl alcohol), followed by 5 parts by weight of 2- (N, N-diamidoamino) -dodecyl 2- (N, N-dimethylamino) -propionate, mixed with ethanol- To the prostaglandin Eι solution, 5 small parts by weight of ethyl laurate were then added.

The preparation of Part B starts from a water / buffer solution with a pH of 5.5, and a sufficient amount of potassium phosphate monohydride 4 potassium (potassium phosphate monohydride) is added to the water in the pond, To produce a 0.1 mol solution, use a strong alkaline solution (1 N 41. This paper size applies the Chinese National Standard (CNS) A4 specification (210X297 mm) 200407149 A7, invention description (two (::: 义)) solution 8. Small portions, all of which are specific here = After V weight is two-in-one ^ ^, add $: 51: 5 small portions by weight ratio to the buffer solution, then rinse the solution and make ^ = v ° cust bean gum ) Spread slowly in the rear part: 1 contains ::: =: mix evenly. Schedule-,, the composition can be coated open, semi-solid preparation suitable for application, stomach without the need for support devices such as patch and adhesive tape The composition is homogeneous in both the resistance and the separation resistance. Other exemplified compositions B to Η are prepared in the same way using the ingredients listed in the attached table, as previously mentioned, in another specific mode example For example, the composition Η, the composition may include a & good polysaccharide gum, ideally a Modified galactomannan gum (galactomannan gum), such as a guar gum (guar gum).

An alternative is to replace polysaccharide gums with polyacrylic polymers. The skin permeability of standing composition A was evaluated using a snake's molting as a model obstacle. The molting of the snake was obtained from the Animal Care Unit of the University of Kansas. Divide into test aliquots and hydrate them by soaking. The samples were then evaluated using a Franz -1 ype Diffusion Cells (surface area 1.8 cm²). The skin fragments were specially installed in a receiver cell combined with a vertical infiltration cell. At the top, a small magnetic rod is inserted and filled with an isotonic buffer. A seal pad is placed on the top of the skin slice, followed by a small supply of 42. The paper size is applicable to the Chinese National Standard (CNS) A4 (210X297 mm) (Please read the precautions on the back before filling out this page). Printed by the employee consumer cooperative ....... 1! I 1 200407149 A7 Β7 V. Description of the invention () ^!-(Please read the notes on the back before filling this page) (donor cel 1), two Koike clamped tightly together. A known number of formulas are placed on the bottom of a small covered injection bottle (weight 0.5 grams) that fits the supply cell just to ensure a consistent spread. The injection bottle is placed on the skin in the supply cell in order to Reduce the amount of ingredients' Use a waterproof tape to stick the supply cell and the injection bottle together. Move the diafiltration tank to a stirred water bath (32 ° C), take samples every hour for a total of four hours, and analyze the concentration of prostaglandin Eι. The change in concentration shows the number of penetrations, and test multiple skin samples The data generated are averaged. For a discussion of the evaluation of drug permeability using snake molting, reference may be made to U.S. Patent No. 4,771,004, Higuchi, which is incorporated herein by reference. Allesin El penetrated very quickly at a relatively continuous rate over four hours. The results of the permeability studies are presented in Table 2 and later.

Example 2: Topical prostaglandin E! Composition B The composition B printed by the consumer cooperative of employees of the Intellectual Property Bureau of the Ministry of Economic Affairs is prepared by using the ingredients listed in Table 1 below. No matter how much substance A is added, composition B shows a uniform semi-solid consistency and uniform appearance regardless of the increase in the amount of the substance. &Amp; The permeability of prostaglandin E! Was measured according to the technical method described in Example 1. Composition B provided relatively fast and sustained delivery of prostaglandin El, the results of which are presented in Schedule II. Example 3: Topical prostaglandin Em composition c Composition C was prepared using the ingredients listed in Table I below. Group 2 contained more than four columns of adenine Em compared to composition A or B, increasing = Medicine = load has little or no effect on consistency or appearance. In fact, the consistency and appearance of composition A or B are actually combined. Prostaglandin & the paper size of this paper is suitable. 43 Chu Gong 7 9 2 200407149 A7, invention description According to the technical method described in Example 1, the pancreatic decomposition composition C also provided a relatively fast and continuous delivery of prostaglandin Ei, the results of which are presented in Table II.

Example 4: Topical Prostaglandin El Composition D Composition D was prepared using the concentrations listed in the following Schedule I and then increased without substantially affecting proper thickening and separation resistance. Prostaglandin £ 1 The permeability is measured in accordance with the technical method described in Example 1, and the results are presented in Appendix II.

Example 5: Topical Prostaglandin Eι Composition E ^ The composition E was prepared using the ingredients listed in Table 1 below. -Human applied to composition E. By the composition of composition e, etc. 2, the semi-solid consistency and separation resistance, its repeatability is substantially confirmed, and the permeability of the four columns of adenine Ei is as described in Example 1. The technical method of measurement again yielded the prostaglandin El line from composition E to be relatively fast and continuous. The results are presented in the second table.

Example 6: Topical prostaglandin Eι composition F 5 列 列 列 素 EI 5: increased in composition j ?, special ingredients in Table 1, proper consistency and resistance to separation have not decreased, permeability The results of the analysis are presented in Appendix II below.

Example 7: Topical Prostaglandin El Composition G Preparation of Composition G # The ingredients listed in Table I are used. For Composition G, the preparation method of Composition F is repeated, except for esters (44 papers per month). Standards are applicable to China National Standard (CNS) A4 specifications (210X297 mm) (Please read the precautions on the back before filling out this page). Order printed by the Intellectual Property Bureau of the Ministry of Economic Affairs and the Consumer Cooperatives.

81

G Η V. Description of the invention () 桎 S Wen B S)) omitted and ^ ethanol concentration increased by a corresponding amount, the resulting composition is also a dispersible, semi-solid, with a uniform appearance and separation resistance The results of the sex analysis are presented in Appendix I below. Although still suitable, these results reflect the relative advantage of comparing the composition of the present invention to a lipophilic compound comprising an S component and an alcohol component. Prostaglandin E1 composition 2.5 (Please read the precautions on the back before filling this page) Water / buffer (pH 5.5) Sucrose hard ^ acid salt 0.5 0.1 81 81 81 81 81 81 81 81 86.8 0.5 0.5 0.5 0.5 0.2 Prostate E1 0.3 0.4 0.4

0.5 0.5 0.5 0.4 0.3 0.2 ίο 2.5 2.5 Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs

Example 8: Comparison of Permeability Data. Attached Table 2 shows that every one hour of each composition sample of the present invention is seletonin E! Permeation accumulated for a total of four hours. These data show the percutaneous delivery of drugs of the present invention. ability. Attached Table 2: Cumulative amount of prostaglandin Ei penetration (μg / cm2 / h 200 407 149 Description of the invention (1. 96 52. 13) Further evaluate the effectiveness of the composition of the present invention, compared to the sample composition. The first comparison sample ( Comparative Shifeng: Example 10 was prepared by the same preparation method as compositions D and E, except for the DDAIP penetration enhancer. For the second comparative sample, Example 2) 'DDAIP was also omitted, but the concentration of ethanol was increased Corresponding amount is applied. The special ingredients used are listed in the following table = a relative table III: Comparative samples

Comparative sample 2 group components (parts by weight ratio) prehydrated carob gum -------- water / buffer (pH 5.5) sucrose stearate prostaglandin Ei 81 Order 0 · Ethyl ethyl laurate was used to evaluate prostate permeability according to the technique described in Example 1. The results are shown in Table 4 below. Table IV of the E !!: Comparison sample cumulative cumulative amount of prostaglandin E! (Micrograms per square centimeter) 1-46 This paper size applies the Chinese National Standard (CNS) A4 specification (210X 297 mm) ^^ ~ 200407149 A7 B7 V. Description of the invention (^ This group 忑 ¥

Example 9: A single-use double-blind and open-label clinical trial of a 0.4% by weight prostaglandin & (prostaglandin & or alprostadil) topical composition (the composition of Example 4 and the attached table are as above) Female holistic and benefit were assessed in three study locations with a total of 143 men. This study included a double-blind, placebo-controlled (lpaceb〇c〇ntr〇iied), and cross-conversion (CrOss -over) group, and an open-1 abe1 group. In the double-blind, placebo control group of the study, 64 people joined and completed Pro Schedule 5. 'Below) '79 people joined and completed the discussion summary of the study below.), Conditions for closing the clinical trial results 1 · male , Ages 21 to 70 years, all inclusive. Yes, the history of dysfunction records, the definition is in the previous 6 months' because of psychological, neurological, or blood = inability to achieve and maintain a sufficiently hard sexual intercourse: this d has a partial erection Elderly, mild to moderate impotence men with erectile dysfunction are diagnosed based on medical history and physical examination (please read the precautions on the back before filling this page)-Ding. 4 ^ · Ministry of Economic Affairs Printed by the Intellectual Property Bureau Staff Consumer Cooperative

200407149 A7 B7 V. Explanation of the invention () Conditions for exclusion 1. Have a history of urethral stricture or obstruction. 2 · Any combined findings from medical history, physical examination, or screening studies that indicate pre-existing impairment of heart, liver, and / or kidney function (eg, congestive heart failure, unstable angina or recent acute myocardial infarction, untreated diabetes, hormones Causes of erectile dysfunction), in the opinion of the investigator, these can influence the results of the study. 3. Medical history of yin, including penile implants (penjie i mp 1 ant), prostatectomy (proMakctojjjy) or prostate cancer, penile trauma including paraplegia or pruritus (extremity paralysis) qUadripiegia). 4 · Any disorders that may be prone to abnormal erections (pr i ap i sm) such as sickle cell anemia, multiple myeloma, or leukemia 1 (1eukemia) °-5 · Hypertension (sitting diastolic pressure> 90 or compressive pressure> 15) needs to be treated with something other than angiotensin converting enzyme inhibitors (ACE inhibitors). 6 · Physical examination confirms the existence of sexually transmitted diseases. 7. Have used a sponge injection or external erection device within four weeks before participating in this study. 8. Peyronie's Disease or any palpable fibrous nodule (fibr oosscar) or plaque; evidence of bending during swelling and hard stimulation, or penile skin Or the glans mucosa is abnormal. · 48 digits. The Zhang scale is applicable to Chinese national standard (〇 奶) 8.4 specifications (210 '乂 297 mm) (please read the precautions on the back before filling out this page),? Τ Employees ’intellectual property bureau consumption Printed by the cooperative, 200407149 A7 B7, Description of invention () (Please read the precautions on the back before filling out this page) 9 · Any drug being taken is known to interfere with sexual activity ', such as antidepressants, Antihypertensive needles, sedatives, hormones, and some allergy medications. 1 0 • Undergoing treatment within 30 days of participating in this study. One sip * 11. Can't or is unwilling to give "informed consent". The patient distribution in this study included males ranging in age from 49 to 70 years. The distribution of patients registered in the study area: one place, second place = place 1, total double-blind 30 34 0 64 open mark 32 8 39 79 after the use of medication 'from the patient's medical history and patient rating questionnaire using a six-point classification scale ( six-p〇int ciassificati〇n The consumer cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs printed sca 1 e) (schedule 6) for clinical benefit assessment. Patients in the double-blind group of the study, each patient was given one (Γ placebo and one (1) active dose in a cross-over fashion, one wash period (⑽ 讣 -〇ff for 5 to 7 days; in the open-label group) Patients are given only one (丨) active dose. Clinically provided is a single dose container, each containing 250 mg (net weight) cream and 1 mg prostaglandin. The effective response ratio is calculated to be sufficient Divide the number of erections by the total number. To be considered successful, the drug must reach 49 waves after application. Chinese National Standard (CNS) A4 specification (210X297 mm) 200407149. 5. Description of the invention () Grades 8 to π, Or the patient must have sexual intercourse. Use a paired test to compare the response level before and after (Paired t-test) method or open the labeling group, it is found that every two ^, whether it is the study of the double-blind red dose level before and after uniform t; Patients with poor significance and drug-producing patients were also found in each of the study sites: (: <0.001. At the same time 'is statistically significant. /, Between the active group and the placebo group also attached Table 6 · 6 points The grade is defined by the severity of Dinggu ’s atopic erectile dysfunction (痿). 2 6 No function _ Very little work | Some functions are mild to moderate impotence Some functions are impotence Patients with all functions recorded Severe Ministry of Wisdom Property double-blind open marking total number of patients with mild to moderate non-impotence consumption cooperatives Yinwu found that impotence men with topical prostaglandin E1 composition for yang therapy are safe and effective: r /, Qiaozheng ratio name ~ 1 :: --- 50 paper size (CNS) A4 specifications "297 public address 200 407 149 V. Description of invention (64.7% to male (66 of 102)) and male employment in light competition (41/41 Patients), overall heart ^ 74.8% (1 07/1 43 patients), shown in the attached schedule 8. 64.6% (51/79) 7% overall ratio (3 / 64T ~ 74.8% (107 / 143) P &lt; 0.001., Prostaglandin E1 composition for ministry for mild to moderate impotence: very effective (100%), mild to moderate impotence, 痿 grade is the most 吝 class. And It is estimated to account for 70% of all complaints of erectile dysfunction, and the study group with severe impotence is also effective (6 4.7%). Of the 7 patients in the double-blind group, who responded effectively to placebo (4.7%), this is much lower than about 10% in other clinical studies: Ϊ: = ratio, this low ratio may be Most of the patients (63%) were classified as severe impotence because of the classification of injury. Although 17 of the 64 patients (26.6%) were printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs, ^ ^ 7 Sufficient improvement can be evaluated as effective (8 to i 0 on a classification level 4 table). In effect

The overall benefit of no patient participation 79.5 ° / 〇 (3 1/39) This paper rule i: Applicable? Standard (see (2ΐ〇χ297_ 200407149 Α7 Β7) V. Description of the invention % (1 3/18) 33.3% (2/6) 51. 3% (2 0/39) 55. 6% (3 5/63) Double blind 100% (2/2) 100% (23/23) 100% (25/25) 100% (14/14) 100% (14/14) 100% (2/2) no patient participated in 100% (16/16) open sample group The effective ratio of the group is low. Table 9) 'The main reason is that the open-label group in this study is compared with Shuangyao, and there are quite a few males with severe impotence (Schedule ▲). Of these, 79.7% (63/79) of the patients were estimated to be severe impotence, while only 9% (39/64) of the patients in the double-blind group were evaluated to have severe impotence. It is expected that those with severe impotence will be blind (please read first) Note on the back, please fill out this page again) Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs 60. == Lower level is because by definition these men have only a few functions = able to 'actually' expect impotence levels from 0, 2 Or 4 shift i 10 Difficult, although most men with severe impotence showed no improvement in 36 men (36/1 02 or 35.3%) who were not sufficient to be classified as effective. The adverse event observed in the study was mild temporary burning; : R; tingling sensation, no side effects of systemic toxicity. "Patients have spouses to report adverse events in the study. None of them are" out of study or not tracked. Real = ten. Multiple open-label clinical trials. " · «3 males and 6 females of a useful composition for safety and benefit before, 5 ° 0 rganic) for men with erectile dysfunction

200407149 A7 ____ B7 Jade; *, Da Ming explained () people participated in and completed this research, imitated π Jiuyi A patients with erectile dysfunction international nfFF ^ Tlti〇Ilal IndGX 〇 'EreCtHe D ^ f-ction (please first Read the notes on the back and fill out this page} :)) The pre-dose sexual encounter file (pr, e dose Sexual Encounter Prof ii P ⑽, ·

Ue (SEP)), grouping them, forty-nine () patients were classified as mild to moderate erectile dysfunction, while seven (7) patients were classified as severe erectile dysfunction, and each patient was required ^ The study was performed in multiple use regimens using 3 to 1 G doses of the drug over four weeks. The overall effective ratio of the mild-to-moderate group is broad. The results of this study are consistent with the overall effective ratio of the previous embodiment IX. No patient withdrew from this multiple use study and no serious adverse events were reported. Conditions for closing the case 1 · Male, ages 21 to 70, both inclusive. 2 · A history of erectile dysfunction, defined as the previous 6 months, because of psychological, neurological or angiogenic reasons, unable to achieve and maintain a sufficiently hard erection during sexual intercourse. This includes patients who still have erections that are good enough for sexual intercourse but not long lasting ’, which is a typical complaint of older, mild to moderate impotence men. The diagnosis of erectile dysfunction is based on medical history and physical examination. Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs. Conditions for exclusion 1. Have a history of urethral stricture or obstruction. 2 · Any comprehensive findings from medical history, physical examination, or screening studies &amp; pre-existing impairment of heart, liver and / or kidney function (such as congestive heart failure, unstable angina pectoris or recent acute myocardial infarction 53 Chinese National Standard (CNS) 8-4 specification (21〇γ297 mm) 200407149 Α7 Β7 V. Description of the invention () Stopper: untreated diabetes, hormonal erectile dysfunction), with the opinion of the examiner 'These meetings Influence the results of the study. .3 medical history of penile surgery including peni le implant, prostatecty or prostate cancer, penile trauma including paraplegia or limb paralysis ( qUadriplegia). 4. Any condition that may be prone to abnormal priapism, such as sickle cell anemia, multiple myeloma, or leukemia. ^ 5 · Hypertension (sitting diastolic pressure> 90 or compressive pressure> 150) requires treatment with angiotensin converting enzyme inhibitors (ACE inhibitors) other than vasopressin converting enzyme inhibitors (ACE inhibitors). 6 · Physical examination confirms the existence of sexually transmitted diseases. 7. Have used a sponge injection or external erection device within four weeks before participating in this study. 〇8 · Peyroni's disease or any fibrous scar or flat lumps (p 1 aque) on the penis; Evidence of bending, or abnormal skin or mucous membranes of the penis. 9 • Any medications that are being taken that are known to interfere with sexual activity ^ 7 'such as anti-depressants, partial antihypertensive tablet sedatives, hormones, and some allergic drugs. 10 • Have been receiving household treatment under investigation within 30 days before participating in this study. σ ____________________ _ 54 This paper size applies Chinese National Standard (CNS) Α4 specification (210 × 297 mm) ~ &quot; &quot; &quot; ~ '(Please read the precautions on the back before filling this page) -5-Θ Wisdom of the Ministry of Economy Printed by the Property Cooperative Consumer Cooperative, 200407149 A7 B7 V. Description of the invention (• 1 1 • Informed consent cannot or cannot be given to the original member) 〇 The patient population in this study included men aged 49 to 70

The erectile dysfunction international index (schedule one and pre-dose sexual encounters file (SEP) six-point classification level (schedule _ one)) was used before and after using music to evaluate clinical benefit from patient history and patient assessment questionnaire. 4 I ,, People give 10 active doses, ask them to take them home, try as many sexual intercourse as possible within one $: 7 rooms, the drug department is special «50 ten early dose dispenser package. (Please read the note on the back first (Fill in this page again)

Severe six-point classification grade is used to evaluate ^ .mw (sEp): 55 This paper is a standard of si transfer standard (CNS) eight 4 secrets (2iGx297 printed by the Intellectual Property Bureau of the Ministry of Public Economics and Employees' Consumer Cooperatives 200407149 A7-_____B7 V. Description of the invention () Classification definition 0 Severe impotence with no function 2 Moderate impotence with a few visits: Yes 4 Moderate impotence and some functions. 6 Mild impotence 8 No impotence but loss of some functions Γ 10 Ignorant cancer Function :: .. The meaning of effective response ratio is the success of the sexual father, divided by the total number of sexual intercourse attempts. A successful determination is that after the administration of a dose of t must reach 8 to 10 or the patient Sexual intercourse must be intentional. Chi Square statistics were used to statistically compare the response levels before and after administration, and there was a statistically significant difference between the dose levels before and after each group of patients receiving the active drug. (P &lt; 0 · 001). 〇 Schedule 13: Patient registration of yang pain severe severe to moderate total number of patients 7 49 56 Schedule 14: Benefits of each type of patient Benefits by number of patients Trial statistics benefit mild to moderate 36/46 (74%) 178/239 (75%) Severe 4/7 (57 ° / 〇) 16/36 (44%) As previously discussed, prostaglandin Eι The topical composition is applicable to 56 paper sizes of China National Standard (CNS) A4 (210X297 mm) (Please read the precautions on the back before filling this page)

B7 Description of the invention (For mild to moderate impotence &amp;, _ impotence grade is the largest part and estimated (74%), mild to moderate m. In patients with severe impotence ... Please read the notes on the back before filling in this page) To be different. Even if serious ;; male 1; posterior: there has been statistically erectile function, 7 males: yes "ff There was no stone I 〇 before the study Four people (57%) had successful sexual intercourse after at least 3 doses of 10 doses. # 埶 知 丨 里 埶 式 =: The adverse event observed in the study was mild temporary burning R ξι 丨 &gt;% + No sense of systemic toxicity and other side effects cannot be regulated, and no spouse reported a patient to withdraw from the study or could not be followed up in the study. Incidents have long-Use group: t ί: The results indicate The prostaglandin El topical product of the present invention is used for patients with mild, moderate to severe yang, and is effective. Embodiment 11: Three-phase clinical research to a three-phase clinical study (Phase 3 Clinical Studies), The topical composition 1 of the First Schedule is also used, and the modified == test composition containing Prostaglandin Eι dosage 0 micrograms (mcg) (placebo), 100 micrograms, 200 micrograms, or 300 micrograms. Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs, /, Remember that the participating patients first receive one for four weeks without treatment Period, and the period of take-home for the next 12 weeks (take_home), refers arbitrarily to one of the four treatment groups · placebo, 100 micrograms, 200 micrograms, or 300 micrograms. Conditions for admission Yes · The patient is at least 21 years old without an upper age limit; has a history of motor dysfunction for three months or more; EF erection range is less than or equal to 2 5; and at least 57 during no treatment 'Paper scales are suitable for wealth management (CNS) A4 specification (21Qx297 male sauce) 200407149 A7 V. Description of the invention (4 attempts of sexual intercourse. Any patient with erectile dysfunction due to the following reasons will be excluded from the study: untreated History of endocrine diseases (untreated endocrine diSease), significant pemle pathology, history of orthostatic hypotension, syncope, and history of syncope Pre-syncope syndrome (pre_sync〇pal symptoms) history (previous 6 months), clinically important liver or kidney disease, myocardial infarction J (within the last 6 months), major neurological diseases such as stroke or Bone marrow injury, recently received erectile dysfunction prescription drugs or medicines or treatments, or have a history of allergies to alprostadil. Patients excluded from the study were patients with a history of prostatectomy, controlled diabetes, taking nitrate medications (nihMe medications ) And alpha blockers (alpha blocckers), and oral PDE5 inhibitors (Sildenaf u, ViagraTM) were not effective. The population distribution and basics of the three-phase treatment group are based on the following Table 15. A known patient may have two types of disease = if-form, and the percentage of "history" will exceed 100%. 0 Intellectual Property Bureau staff, Ministry of Economic Affairs The consumer cooperative printed three-phase clinical research is based on an arbitrary, placebo-based, double-blind study design, and concurrent treatment design including a study of patients with homeopathic to severe erectile dysfunction. In the United States, two separate studies were conducted at M sites. The patients were 1,732 men aged 187 to 87 years, of whom 1410 completed the study. The dropout rate was 18%. Patients were arbitrarily assigned to four simultaneous parallel = 1 treatment groups: placebo, 100 micrograms, 200 micrograms, or 300 micrograms of adenin El dose, starting with a four-week no-treatment period, followed by. f home dose, each patient has 25-58 200407149 during the twelve-week treatment period V. Description of the invention (doses, in this study, forgetting one in four people, its IIEF erectile function = 2, re-erection, function Obstacle problems 1, 2, 3, 4, 5, and Tu Xi at or equal to 25, HEF ΰ and 15 were added to the study. The distribution summary is added in Table XV. "I have a history of two or more diseases. Schedule 15: Age of the mouth distribution in the treated population &gt; 65-* Sakizaki L 0 15% Origin of erectile function range level 13. 8 History of erectile dysfunction &gt; One-year medical history 93% Diabetes 21% South blood pressure 44% Heart disease 28% Lithostearate and A-blocker 16% Prostate resection 12% Oral Sildenafil is not effective 18% (Please read the precautions on the back before filling this page) '、 The composition of the four smelting and healing ethnic groups printed by the Employees' Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs is summarized in Schedule XVI. It should be noted that there may be two types of patients in Department I: a history of sickness. Table 16 ^ mouth points f and starting point characteristics

200407149 V. Description of the invention (A7 B7

(Please read the notes on the back before filling this page). The end point for measuring primary efficacy is: compared with the placebo group, the erectile function international index (丨 丨 EF) erectile function range level, from the beginning to the Changes in the last visit; sexual encounter files (se㈠door delivery 1 · You are not enough to insert your penis into your partner's vagina 丄) and ask Tong Er ·· Does your erection last long enough for you to have sexual intercourse? And ejaculate? ”In response to these two questions, the average response order of each patient was compared with the placebo ethnic group. The Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs printed out its end-of-person efficacy measurement including a whole (Global Assessment Question; (JAQ): "Is your erectile condition improved when using drugs from the study day?" Coordinate with other levels on 11EF. Π Erectile dysfunction specified by the level of erectile function range The severity is as follows: Severe (<u), moderate (n-16), mild to moderate (17-21), mild (22-25), or normal (&gt; 26). Of the four treatments Efficiency measures 丨 丨 EF The changes in the range of erectile function range are shown in Appendix XVII and are limited to patients who have completed the study. This paper size applies the Chinese National Standard (CNS) Α4 specification (210X297 mm) 5. Description of the invention The full_family_ drought private group produced the greatest effect, the same level as placebo of 0.001. 疋 It is meaningful that all doses are different compared to placebo. The number of patients is the same. The overall evaluation question, " Do you feel that your erectile condition has improved when using research-based drugs? The response (see Table 18 below) also shows a difference from the placebo group, all PG. The dose level has p &lt; 0 · 0 0 A level of 1. Do you feel that your erections have improved when you use Scheduled 18 drugs printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs? 20 n = 394 1 0 0 micrograms 40 (p &lt; 0.001) 200 micrograms 47 ~ (ρ &lt; 0 · 001) 300 micrograms 52 (ρ &lt; 0 · 001) This paper size applies to China National Standards (CNS) A4 size (210x297 public attack)

ZUU4U / 14V A7 &amp; Li ϊ ϊ 案? Case (SEP) Question 3 about maintaining an erection to ejaculation = i ϋ π ϋ ding, Schedule 20), in the difference between the two higher dose groups and the female placebo A 士 w Yue # 我 4 幻 产 / 、 4 Ρ &lt; 0. 001 level, but the difference of 100 micrograms of straight bismuth group is in the range of 0.003. Attached Table 2 + V. Explanation of the Invention (SEP) Q: 'The ability of the vagina, Shi ^ ^ Shizhu a about the difference between the penis inserted into the sexual partner Sagittarius I pay table + bad, .β, all PGE1N Α IX), also showed a range of P &lt; 0.001 with the placebo population 1 *. (Please read the precautions on the back before filling out this page) Order Φ. Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs ------- The difference between the percentage of patients with successful sexual intercourse compared with placebo Meaning of patients Placebo 30 Ν = 411 100 mcg 39 (P &lt; 0.003) Ν-418 200 mcg 42 (P &lt; 0.001) Ν = 410 3 0 0 mcg 39 (P &lt; 0.001) NR = 410 〇_ The number of patients placebo ~~~-51 100 mcg 57 s ^ g ^ O · 0 01)-sigl0 · ooi)-Ν = 411 2 0 0 mcg --- ~~~ 58 Ν 2 418 3 0 0 micrograms ^ ~ ----- ^ 58 Ν = 410 --- J Ν = 41 0 62 Wood paper standards are applicable to China National Standard (CNS) Α4 specifications (210 × 297 public meals) 200407149 A7 B7 I. Description of the invention ( A summary of the end points of the primary efficacy of the secondary participants can be found in Appendix 21 below. The overall change using PGE! Treatment is a significant difference compared to placebo. The Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs printed the end points of Schedule 20. Summary of Major Efficacy Variables Treatment Population Placebo (N = 416) 100 micro (N 422) (N = 412) 300 μg (N-419) Overall / 7 value End point Change End point Change End point Change End point Change primary efficiency ~ End point I IEF, Erectile function average change from the start point 13 · 3-07 15 · 3 1 · 6 16 · 1 2.5 16. 1 2. 5 <0 · 0 01 SEP level, the average success rate of each patient from the starting point% Question 2 (Ability to reach erection) 51.2-4 5 56. 6 2. 9 58. 2 5 · 1 57. 5 7. 2 0.00 2 Question 3 (Keep up 30. 2 0. 4 38. 9 7. 0 41. 9 13. 8 38. 5 9. 1 &lt; 0 · 001 Μ specifications (2 · 10 · ^ ¥ Τ (please read the precautions on the back before filling this page), 1T line ·-200407149 A7 B7 V. Description of the invention (up to the ability to ejaculate) Secondary Overall evaluation of efficacy end point 20 40 47 52 &lt; 0. Questions,% of patients who answered "yes" (Does the medication improve your erection? Yes / No) 001 (Please read the notes on the back before filling this page)

The percentage of patients achieving normal IIEF grade (&gt; 26) after treatment was 6% (placebo), 10% (100 micrograms), 14% (200 micrograms), and 16% (300 micrograms). Example 12: Treatment of erectile dysfunction in diabetic patients Evaluation of therapeutic efficacy of subgroups of patients with a history of diabetes Digestion fT Schedules 22 to 23, the efficacy of the four treatment methods is EF erection Changes in functional range were measured and shown in Schedule Twenty to be completed by investigators in the subgroup of diabetic patients. The two higher doses of the Hippocampus $ group produced the greatest effect. Compared with placebo, the grade difference was #Si, Yi, and all doses were in the range of ρ <0.05. Function range

Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs

200407149 V. Description of the invention (average change in beam gas compared with the difference meaning placebo 1 0 0 micrograms-2-2-------Ν = 81 2 · 1 (P = 〇 · 014) Ν = 90 200 micrograms 3.7 (P &lt; 0 · 001) Ν = 94 300 micrograms 2.4 (ρ = 0.003) Ν = 95 For the overall floor value question, "Do you feel that Is there an improvement in the erection situation? The response (see table 13 below) shows a difference from placebo. For all doses of pGEi, the p value is in the range of <0.01. Table 23: Diabetes The overall patient evaluation question "Do you feel an erection when using the planned drug? The difference between the percentage of patient improvement and placebo is significant. The number of patients placebo 20 Ν = 76 1 0 0 mc43 (P = 0 · 001) Ν = 69 200 mcg 45 (P &lt; 0 · 001) Ν = 92 300 mcg 53 (P: 0 · 001) Ν = 79 Response to Sexual Encounter Profile (SEP) Question 2 regarding the ability to insert a penis into a partner's vagina (Annex 24 below), any p dose compared with placebo did not show a meaningful difference, its p The range of $ 0 · 05. '(Please read the notes on the back before filling this page), 1T-line · 65 copies printed on paper by the Intellectual Property Bureau Staff Consumer Cooperatives of the Ministry of Economic Affairs. Applicable to China National Standard (CNS) Α4 specifications (210 × 297 mm 200 407 149 A7 V. Description of the invention (the difference in p-channel energy 1 in patients with sexual intercourse success ratio compared with placebo Significance --------------- one-'' response to the number of patients placebo ------— 1 0 0 micrograms ~~ ττ— ^ P ^ O. 123 ~ &quot; &quot; ------ -N = 84 ~ ----_ 200 micrograms _N-90 300 micrograms-p = 0. 002 __N = 95 P = 0.253 —------ N = 83 --- 1_ (Please read the precautions on the back before filling out this page) For sexual encounters (SEp) problem III ability to ejaculate The response (the following table 2 holds the work I up to the dose, and there is a significant difference with respect to the hand and right Mingneng & in the 200 micrograms /, Τ ... ,, and (ρ &lt; 0 · 005) Attachment 25. The ability of diabetic patients to experience the results of their archives ”^ 孓 Ordered by the Intellectual Property Bureau of the Ministry of Economic Affairs, Consumer Cooperatives, printed placebo 300 micrograms 36 46 33 p = 0.123 P 0.20 002 p = 0.253 N = 90 N = 95 N = 83 Example 13: Treatment of erectile dysfunction in patients with prostatectomy For patients in the subgroup who have a history of prostatectomy, the treatment & Zhang scale is applicable to China (210X Erli 200407149 A7 ___________B7 V. Measurement of the effect of the invention () The summary of the measurement is shown in the following appendixes 26 to 29. The effectiveness of the four treatment models was measured by the 'changes in the range of erectile function of the IEF of this ethnic group of patients who completed the study. It is shown in Schedule 27. The two higher dose groups produced the greatest effect, and comfort. The dose groups were compared, and the levels of difference were significant. All doses were in the range of p &lt; (K Oi.) Table 26: Erectile function of prostatectomy patients from the beginning to the end, the average change and comfort The difference in the comparison of doses means the number of patients. Placebo-2 · 2 Ν = 46 100 μg 2.2 2 (ρ = 0.004) Ν 71 200 μg 2. 4 1 (P = 0.006) Ν = 44 300 μg 2.5 (ρ = 0.003) Ν = 51 In response to the overall evaluation question, "Do you feel an improvement in your erections when using the planned drug?" (Annex Table 27 below) shows the difference from the placebo For all doses of PGE !, the p-value is in the range of &lt; 〇 001. (Please read the precautions on the back before filling out this page) Order the printed paper attached table 27 of the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs : Overall evaluation of prostatectomy patients "Did you feel an improvement in erections when using the drugs in the study period?" The difference between the percentage of patients responding to the improvement of patients and the number of patients compared with placebo is 67 sheets. The standard applies the Chinese National Standard (CNS) A4 standard (21 〇 × 297 male diamond) 200407149 A7 B7 V. Description of the invention (meaning J placebo 11 1 ο ΰ microgram 47 (ρ &lt; 0.001), 200 microgram 57 (ρ &lt; 0.001), 300 microgram 55 (ρ &lt; 0.001) '

For Sexual Encounter Profile (SEP) question two, the response to the ability of the partner's vagina (Table 28 below) Comparing 'only a dose of 300 micrograms of P G E1 shows a meaningful p value in the range of &lt; 0.01. The difference between penile insertion 'and placebo. Schedule 28: Sexual restraint in patients with prostatectomy. [Performance of penile insertion into sexual partner's vagina. Successful percentage of patients. Percentage of patients compared with placebo. Meaning Placebo 21 1 0 0 mcg 41 ρ = 0 · 1 29 200 mcg 35 ρ = 0 · 1 5 5 3 0 0 mcg 36 ρ = 0. 0〇6 Results of patient count case-45 -71 N-45 Employees ’Intellectual Property Bureau, Ministry of Economic Affairs Printed by the cooperative = 51 Response to the Sexual Encounter File (SEP) Question 3 on the ability to maintain erectile ejaculation (Annex Table 29 below), at 300 micro doses, there is a significant difference with the control group.

P 056) Nineteen: Prostate resection patients with sexual encounters with archives and the ability to maintain an erection until ejaculation "(please read the precautions on the back before filling this page)

I cake Zhang scale Shicai Guanjia County (68 200407149) Description of invention (percentage of patients with a successful ratio in ten years of life compared with placebo

::: Shiji · Treatment of erectile dysfunction in patients undergoing phlebectomy. For the treatment of erectile dysfunction in patients who need to be treated with Pore King's resection and neuropreserving prostatectomy, the semi-solid prostaglandin composition of Example 10- is used, although Treatment can be started at any time after prostatectomy, but it is ideal to start treatment about one to six months after the operation. According to the severity of erectile dysfunction assessed by IIEF, a regular treatment regimen is required, and no connection to the sexual intercourse is required. A semi-solid vasoactive prostaglandin composition can deliver about 100 micrograms to about 400 micrograms of prostaglandin E1, which can be applied to the scaphoid fossa of the penis at least twice a week, or every other day, or once a day. For "on demand" treatment, the semi-solid vasoactive prostaglandin composition should be applied to the scaphoid fossa of the penis 2 to 30 minutes before intercourse, preferably 5 to 15 minutes before intercourse. After about three months of treatment, about 40 to 60 percent of patients receiving treatment reported that they felt an improvement in their erections when using the drug. Example 15: Treatment of erectile dysfunction in patients with erectile dysfunction that is ineffective with oral phosphodiesterase-5 inhibitors 69 This paper size applies Chinese National Standard (CNS) A4 (210X297 mm)

(Please read the notes on the back before filling in this page J

1T Φ. Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs. ΓΙ Schedule 30200407149 V. Description of the Invention (Disorders: Dilipase-5 inhibitors have no effect on erectile dysfunction, the following schedule 30 The measurement summary of its treatment effect is summarized in &amp; Tannuzhi: &quot; to thirty-three. The benefits of the four treatment modes are measured by complete green, and the change in the range of IIEF's erectile function in patients of ί ethnic group = two times The statistics of the patients who completed the study showed that the highest dose levels of Yu Er's two had the greatest effect. Compared with the placebo group, each surname had a range of P &lt; 0.05. The difference is not significant. Oral Sildenaf i 1 treatment is not effective for patients with erectile dysfunction. (Please read the precautions on the back before filling this page)

-^ 1 --- 1 II ------ The difference between the average change from the start point to the end point compared with placebo Significance Number of patients Placebo-0 · 4 Ν-80 100 µg 1 · 2 ρ = 0 · 134 Ν = 83 200 micrograms 1. 7 Ρ &lt; 0_ 061 Ν = 7〇300 micrograms 1. 4 Ρ &lt; 0 · 097 Ν = 78 Order the issue of the overall evaluation printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs, "In use Do you feel any improvement in your erections when studying daily medications? The response (see Table III-1 below) shows a difference from placebo. For the doses of 200 micrograms and 300 micrograms of PGEi, their p-values are all in the range of <0.05. Schedule 30: For the erectile dysfunction patients whose oral Sildenaf i 1 treatment is ineffective, the Chinese National Standard (CNS) A4 specification (210X297 public shame) is applied. 200407149 A7 _________B7 V. Description of the invention () The overall evaluation problem is in use Did you feel your erectile dysfunction improved when studying the planned drugs? The difference between the percentage of patients responding to the improvement compared with placebo is significant. ^ Placebo Τϊ ~~ —— ---__ 100 μg 29 ρ = 0.158 2 0 0 μg 37 ρ 2 0.025 3 0 0 μg 45 ρ = 0 · 001 Ν = 73 f Please read the notes on the back before filling this page) Response to Question 2 of the Sexual Encounter File (SEP) regarding the ability to insert a penis into the vagina of a sexual partner (Table 32 below), Compared to placebo, 200 micrograms and 3300 micrograms of PGE! Dose showed a significant difference, with p values in the range of $ 0.05. Attachment 32: Response to the results of sexual encounters in patients with erectile dysfunction who have failed oral Sildenafi 1 treatment. "The ability to insert the penis into the vagina of a sexual partner." Difference from placebo Meaning Number of patients Placebo 43 N = 80 1 0 0 micrograms 45 ρ = 0 · 181 N-83 200 micrograms 45 p = 0 · 0 4 6 N = 70 300 micrograms 49 p = 0 · 0 0 4 N = 78 This paper size is applicable to China National Standard (CNS) A4 specification (210X297 mm)

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200407149 V. Description of the invention (anti-friction Y for the ability of sexual encounter files f fine Y question two about maintaining an erection up to M under ρ fu fu yi yi, dosage, and control group clothing twenty-two), at 300 micrograms of guard / There are obvious differences. Attachment 33: For the oral erection of I enaf 11, the treatment of erectile dysfunction can lead to premature dysfunction in patients. Sexual encounter file results Example 16 • Treatment of erectile dysfunction in patients with hypertension is high for subgroups For patients with a history of blood pressure, the measurement of the effect of treatment is summarized in the following schedules 34 to 37. Four treatment phases: The type of $ owing benefit is measured by the change in the range of IEI f erectile function of the patients who completed the study in this ethnic group. It is shown in Table 34. The two higher dose groups produced the largest effect, and Compared with the placebo group, the differences in the results are significant. All doses are in the p &lt; 0.05 range, and the 200 and 300 microgram doses are more significant, with p values in the range of &lt; 0.001. 72 This paper size applies to Chinese National Standard (CNS) A4 size (2mm) X 297mm) (Please read the notes on the back before filling out this page) -Order · -Φ Printed by the Employees' Cooperative of Intellectual Property Bureau of the Ministry of Economic Affairs 200407149 A7 V. Description of the invention (Annex 4: The average change of the erectile function dustpan from the start point to the end point of hypertensive patients and the difference between the placebo and the significance of the number of patients placebo -0.6 ----------- Ν = 187 1 0 0 micrograms 1 ρ = 0.022 Ν = 185 200 micrograms 2.9 ρ &lt; 0 · 001 Ν = 175 300 micrograms 2. 0 ρ &lt; 0.001 Ν = 196 For the overall evaluation question, Improvement 5) P values showing differences from placebo are all in the range of &lt; 0.001. Use the research plan? ”For all, three &quot; timetables, substances, supplements, and medicines with E1 i c .. Ρ

(Please read the precautions on the back before filling out this page.) Attachment 27: Questions about the overall evaluation of patients with hypertension Do you feel any improvement in your erections when using the medicines in the research project? The difference between the percentage of patients who responded to the improvement and the placebo was significant. The number of patients placebo 20 N = 178 100 μg 37 ρ &lt; 0.001 N 2 178 200 μg 47 ρ &lt; 0 · 001 Ν = 173 300 μg 49 ρ &lt; 0 · 001 Ν 2 187 Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs on the Sexual Encounter File (SEP) Question 2 Response to the ability to insert a penis into the vagina of a sexual partner (Schedule 36 below), with 73 placebo papers The scale is applicable to the Chinese National Standard (CNS) A4 specification (210X297 mm). The significance of comparison with placebo p = 0 · 0 3 8 ρ &lt; 0 · 001 ρ = 0 · 0 0 5 189 Description of the invention () Comparison, all PGEl Dose &lt; 0.05 range. There is no difference in meaning, its p value is in the thirty-sixth table: the response of high "the ability to insert the penis into the sexual body f patient sexual encounter file results vagina" number of patients placebo 100 micrograms 200 micrograms 300 micrograms Encounter file (SEn's response to the ability to recognize ejaculation (see the following table 317 erection until the film) "there is a significant difference between a pair of makeup groups (p = 〇〇〇01) Where Table 37: Hypertensive patients Sexual encounter file results (please read the notes on the back before filling this page)

、 1T Percentage of patients printed with placebo sexual intercourse successfully printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs ---------- 26 ^ Placebo ιϊΓ Significance of difference ^ Response-100 micrograms of patients 35 ρ = 0.329 Ν = 182 200 micrograms 41 ρ = 0 · 001 N = lTT ^ 300 micrograms 35 ρ twenty 0 · 34 Ν = 195 Example 17: Treatment of erectile dysfunction in patients with heart disease 74 200407149 A7 V. Description of the invention () For patients with a history of heart disease in the sub-group, the measurement results of the treatment results are summarized in the following appendixes 38 to ~, and Q Ding Yi. The benefits of the four, palliative care models were measured by changes in the range of hefq erectile function in the patients who completed the study in this ethnic group and are shown in Table 38. The higher dose groups produced the greatest effect, and the placebo group By comparison, 2 differences in results are significant, all doses are around p <0.05. * The average change in erectile function range from the beginning to the end of the disease in patients with Schedule 38 is different from the placebo. Significance Number of patients Placebo-1 · 7 N = 115 ^ 100 μg 1.4 P = 0. 002 N = 107 ~ 200 micrograms 1.5 p = 0.001 N = 122 ^ 300 micrograms 1. 9 P &lt; 0.001 N = 135 For the overall evaluation question, "Do you feel any erections when using the drugs in the research day? improve? The response (see appendix 39 below) shows a difference from placebo. For all doses of PGEi, its p-value is in the range of &lt; 0.005. , 乂 Please read the notes on the back 顼 before filling out this page}

_I_JJ This is printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs Schedule 39: Overall Evaluation of Heart Disease Patients "Do you feel an improvement in your erections when using the medicines in the research project? 』Response of improvement of patients compared with the percentage of patients compared with placebo 75 200407149 Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs A7 ____ Β7 V. Description of the invention () Difference meaning placebo 17 Ν II 111 100 micrograms 35 ρ <0 · 003, N = 104 2 0 0 micrograms 48 ρ &lt; 0 · 001 N = 116 300 micrograms 50 0 ρ &lt; 0 · 001 N 2 126 For the Sexual Encounter File (SEP) Question 2 regarding the ability to insert the penis into the vagina of a sexual partner Response (Table 40 below), compared with placebo, only 200 micrograms of PGEi dose showed a significant difference, and its p value was in the range of S 0.05; however, the difference of 300 micrograms of PGEi! Dose compared with the control group was significant at p = 0. 054. Schedule 40: Results of sexual encounters in patients with heart disease "Canama sexual intercourse success rate of ability to insert penis into sexual partner's vagina. Percentage of patients compared with placebo Significance Number of patients placebo 44 Ν = 117 1 0 0 microgram 54 ρ = 0 · 109 N = l05 2 0 0 microgram 54 ρ = 0.018 Ν = 125 300 microgram 51 ρ = 0.054 Response to Question 3 of the Sexual Encounter File (SEp) regarding the ability to maintain an erection until ejaculation (Annex Table 4 below) Eleven), the two higher amounts were significantly different from the control group (ρ &lt; 0.05). 1T (Please read the notes on the back before filling this page)

Schedule 41: Results of Archives of Sexual Encounters in Heart Patients

200407149

V. Description of the invention (Ability of Vitamin Essence) Winter Reactive Interaction ^^ ^^ ^ Rate Percent of Patients Placebo 100 μg 200 μg 3 0 0 μg Comparison with placebo Significance Number of patients 23 33 36 31 117 ρ = 0.260 ρ = 0.003 ρ = 0.022 N = 105, N = 1 25 N = 1 30 Example 18: Measuring the efficacy of treatment with the severity of the erectile dysfunction starting point and comparing the severity of the initial point Analysis, there are two studies, including three-phase study. Severity starting point is defined according to the IIEF erectile function range progression: severe (1-10), moderate (11-18), mild to moderate (17- 21), mild (23-25) 'The results are summarized in the following forty-two to forty-six. Schedule forty-two is based on the severity of the starting point from the starting point to the ending point at the level of the IIEF erectile function range. Changes in Numbers (Study 1) (Please read the notes on the back before filling out this page) The Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs prints mild to moderately severe placebo-4 -1.9 -0 · 4 2 · 5 100 μg-0 · 5 -0 · 7 2. 3 4. 1 200 μg 1 1. 1 2. 9 4. 9 300 μg-0.2 1.6 3. 8 5. 1 ~ Attachment 43. 77 This paper size applies to the Chinese National Standard (CNS) A4 specification (210X297 mm) 200407149 A7 ___ B7 V. Description of the invention () From the starting point of the severity evaluation value from the starting point Changes in the range of erectile function to the end point at 11EF (Study 2) V Mild Mild to Moderately Severe Placebo-4 · 8 -0 · 7-0 · 1 0 · 6 _ 1 0 0 μg- 1. 6 0. 3 1. 5 4.6 2 0 0 microgram-3 · 1 2. 9 2. 7 2. 5 300 microgram -0.4 1. 2 1. 5 3. 4 (Please read the notes on the back before filling (This page) The forty-fourth table evaluates the success rate of vaginal insertion treatment based on the severity of the starting point. Sexual encounter file problem two / Sexual encounter file problem one (insertion success / attempt) Percentage (Study 2) Mild Mild to Medium Moderately moderate placebo 77 · 7 68. 3 51. 2 23 · 1 100 μg 90. 5 72. 8 60. 4 25. 9 2 0 0 μg 83. 9 82. 5 62. 6 25. 4 300 μg 88 · 4 78. 9 63 · 8 33. 2 • ^ 1 Schedule 45 printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs, with a starting point severity rating of the successful completion of sexual intercourse treatment rate encounter file problems three / Sexual encounter file problem one (number of ejaculations completed / number of attempts) Percentage of successful patients (study two) Mild mild to moderately severe. Degree 78 'Zhang scale applies Chinese National Standard (CNS) A4 specifications (210X297) (Centi) 200407149 A7 ___ __ ____B7 V. Description of the invention () Placebo 62. 6 47. 6 27 · 4 10. 3 1 0 0 μg 73 · 5 48. 6 38. 2 17. 3 20 0 μg Π. 9 63. 7 41.4, 23.9 9 0 0 mcg 75.7 61.9 37. 7 15. 4 (Please read the notes on the back before filling out this page) Example 19 · Integrated Security Analysis Integrated Security Analysis ( The results of integrated safety analysi are presented in the following schedules 46 to 47. Summary of Adverse Events Related to Treatment

_I_P Intellectual Property Bureau of the Ministry of Economic Affairs, Consumer Cooperatives, printed treatment groups, comfort 100 micro 20 0 micro 300 micro total doses gram gram N = 1732 N = 434 N two 434 N = 434 N = 434 at least one drug phase 61 (14) 156 (36 187 (20 188 (42 592 (34 patients with adverse events, number of people) (%))))) Serious adverse events related to music, 0 0 0 0 0 Patients who stopped due to drug-related adverse events, number (%) 1 (1) 10 (2) 14 (3) 26 (6) 51 (3) 23% of patients have drug-related adverse events Penile burning 26 (6) 76 (18 106 (2 101 (2 309 (1) 5) 3) 8) 79, Zhang scale is applicable to Chinese national standard (0 milk) 8 4 specifications (210 '/ 297 mm) 200407149 V. Description of invention (A7 B7 Penis redness 9 (2) 33 (8) 39 (9) 49 (11,) 121 (7) Genital pain 2 (α. 5) 48 (11) 67 (16) 76 (18) 193 (1 1) Vaginal burning 7 (2) 15 (3) 30 (7) 18 (4 ) 70 (4) Schedule 47. θ MH events related to adverse events and the number of patients with adverse events interrupted (Pan) Burning of the penis 15 (0.9) Penile swelling 21 (1.2) Genital pain 4 (0.2) Vaginal burning 3 (0.3) Other 8 (0.5) Total, number of people (percentage) 51 (3) (Please read the precautions on the back before filling out this page), 1T Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs. This treatment does not have serious side effects, big: good events are limited to the application location but are mild, short in time and i. Overall, the treatment shows that the efficacy can span a wide range of energy disorder severity, that is, more than two disease conditions Example 20: Treatment of patients with hypertension also receiving type A inhibitors. A measure of the effect of treatment on patients with subgroups who have a history of hypertension and who also use alphal blockers. I sheet of paper

Φ. 200407149 Μ ----—__ Β7 V. Description of the invention () ^^ ~ --- ~ — The abstract is attached to the following forty-eight to fifty-one. T Tian Yu reported that the number of samples is small ', which limits the calculation of the P value used to compare differences. The benefit of the four treatment modes is based on this. The changes in the range of IIEF erectile function of patients who completed the study in the subgroup were measured. It is shown in Table 48 that the 300 microgram dose group produced the greatest effect. Compared with the placebo group, any dose The difference is meaningless and its p value is in the range of &lt; 0.05. (Please read the precautions on the back before filling out this page} Schedule 48: The difference between the average change in the erectile function range from the beginning to the end of the patient ^ and the difference with placebo Significance Number of patients Placebo-1 · 2 Ν = 27 100 μg 0 · 0 〈0 · 619 Ν = 24 200 μg-0 · 2 Ρ &lt; 0.543 Ν = 26 3 0 0 micrograms 2.2 ρ &lt; 〇 · 112 Ν = 25 — no matter how small the sample size, the overall evaluation question , "Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Research

Is it nine or ten, ten, four, and the amount of the medicine attached to the table? The amount of the drug is small in the daytime C ο the CO should be the opposite of J? Is it good to change the physical blue?

In the difference. Anal 5 ο ο ο ο show obvious, value) P Schedule 49: Questions for overall patient evaluation 『Did you feel any improvement in your erections when using the drugs planned for the study? The response of patients compared with placebo The number of patients Percent difference Significance

Responses to the Sexual Encounter Profile (SEP) Question 2 regarding the ability to insert the penis into the vagina of a sexual partner (Table 50 below) did not show significant differences compared to placebo, and its p-value was not <0 at any dose. · The range of 05. 200 micrograms and 300 have the greatest effect for the gram. (Please read the notes on the back before filling out this page.) Printed in Schedule 50 by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs. "Partner's ability to vagina" response to successful sexual intercourse ratio. Percentage of patients compared with the starting point. The average change compared with placebo. Significance. ; 0.266 N = 24 20 0 micrograms 47. 3 4. 8 p &lt; 0.327 N = 26 300 micrograms 59. 5 6. 7 p &lt; 0. 151 ^ ------ N = 26 For Sexual Encounters File (SEP) Question 3: The response to the ability to maintain an erection until ejaculation (Table 51 below) is not significantly different from placebo. This paper size applies to China National Standard (CNS) A4 (210X297 mm)

, 1T

Description of the invention (Schedule 5 Placebo 100 μt_200 μ ^ 300 μg 34.3 34.1. 1 / Patient Sexual Encounter Archive Results h \ \ ± ^ Significant difference compared with placebo than patients N = 28 ρ &lt; 0 · 140 Ν = 24 ρ &lt; 0 · 317 Ν = 26 ^ Ρ &lt; 0. ^ 559 ------- Ν = 26 —_ (Please read the precautions on the back before filling this page) 豳 drugs: ί: The analysis is made for ethnic groups with a history of high A pressure and taking four times, but because the sample size is too small (1 yes, 2: 22 patients in the treatment group), it cannot provide useful resources to enter the scope and spirit of the following patent applications Those who belong to the present invention belong to the present invention. Carcass pull-out example, and 11, with appropriate rule paper Yin national standard (CNS) A4 specification (210X297 mm) 200407149

[Explanation of the drawings] [Schematic illustrations] Each drawing: /, the first drawing is a diagram of the longitudinal section of the human penis; the second drawing is a diagram of the longitudinal section of the detail of the end anatomy; the second drawing is a diagram Illustrate preparation. Flute-Λ cause, S solution depicts the local administration of prostate pressure. Ί Pressure: / Control the opening of the urethral opening (-): 2 2 sides of the urethra 'then open the urethral opening method'. Insert the drug into the urethral orifice of the opening ^ triple B picture. "、, 々 will be printed by the consumer co-operative society of the Intellectual Property Bureau of the Ministry of Economic Affairs of the Ministry of Economic Affairs 011123334455688881 L 11 11 11 11 11 1i 1i -1 11 lx 11 11 1i 11 ii 1i 1i 2 The yin of the single stem and simple stem · Symbol element 4 0 2 4 8 0 4 8 0 8 6 8 0 0 2 4 6 0 0 »'I II 2 2

Opening under the drooping mouth of the area: J: Research A sea 4 open urinary mouth muscle body capsule to the bulb opening body-shaped cotton wall tube gland gland sugar sugar layer finger-like stem stem stem cotton wool Sequential hepatic cirrhosis ^ refers to the presence of horns near the yin, yin, yin, sea, and globus before the shot, with or without horns D w W Squamous angled column non-non-shaped device medicine hand (please read the precautions of the North Θ before filling this page)-order 84 This paper size applies to China National Standard (CNS) A4 specification (210X297 mm)

Claims (1)

200407149 A8 1 B8 C8 __________ D8 Application Special ~ ~ ------- ~ '[Scope of patent application] ~ 1 · A method for treating erectile dysfunction, which includes two or more diseases, including rice : ^ Erecti0n-inducing information is placed on the patient's boat, the semi-solid C is a vasoactive prostaglandin; a penetration enhancer; a polymeric thickener, selected from the group consisting of — A family of sugar gums and a polyacrylic polymer with one more lipophilic component selected from the group consisting of an alcohol to C8, an aliphatic to c3Qg, 1C, their mixtures; and $ σ — an acidic buffer system. --------- ·! (Please read the precautions on the back before filling this page) 2 The 4th column of gland. Around the list of the frontal glands of the front 19, the Liheli system, the A1A2 pre-mixed hormone A1, the hormone I, please ask for the glandular gland ^ It is listed as the top 19 and the family Pre-primary, 2 &gt; :: α.χ live, base E AF3 tube E1 dioxin t * hemoglobin 9 gland ^. The middle gland M is listed in front of the front 1α, front and front, method: prime β1Λh square The 19 glands of the prostaglandin gland include 1 gland, 1 gland, 1 gland, 1 gland, 2 gland, and 2 gland. Item E1 1 Gland perimeter Fan Qianhe Department of the Department of Gastroenterology asked the gland to apply as listed above 3 P. Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs' t • blood t in the amount of ° / ot, IX method 00 It weighs the total weight of the first item in the Encircled Group. Fan Yixian's profit system is an exclusive ratio, please refer to the amount of gland, as stated before 1 ° / 0 4 5 6 · Method as claimed in item 1 of the scope of patent application, wherein blood 85 f &gt; tongue The scale is applicable to the Chinese National Standard (CNS) A4 ^ (21〇χ ^^ 200407149 ---_- level patent scope 'The amount of phylatonin is approximately .., mg to approximately. · 3 mg. 7 temples, its towels are polymerized. 8 Hdf 111 d U m polymerized gumming. Shred-thinning polysaccharide tree 9. Qi Λ Please Λ1 Λ around the method called in item 8 where the thinning of the sugar tree Gum is a galactomannan gum. 10 The method referred to in item j, wherein the method of shearing rare-type artificial semisynthetic galactomannan poly 1 is called artificial, where artificial = mouth-forming nougat-mannan Gum is a kind of artificial semi-synthetic melon gum. 1 2. The method as claimed in item 1 of the patent scope, wherein the composition has a viscosity of about 5,000 centipoise (cp s) to about 2 0 0 0 0 centipoise. 1 3. The method as claimed in item 1 of the scope of the patent application, wherein the composition has a viscosity of from about 7,000 centipoise to about 13,000 centipoise. The method as claimed in item 1 of the scope of the patent application, wherein the penetration enhancer is selected from the group consisting of an alkyl-2- (N-substituted gas group) -chain Alkyl-2- (N-substituted amino) -alkanoate, alkyl-2- (N, N-disubstituted amino) -chain -alkanol alkanoate), one (N-substituted amino) -alkanol alkanoate ((N-substituted amino) -alkanol alkanoate), one alkyl-2- (N, N-bis-substituted amino)- Alkanol alkanoate 86. Paper size is applicable to Chinese National Standard (CNS) A4 (210X297 mm) -------- # 1 — (Please read the precautions on the back before filling this page) Order Printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs. 4 200407149 A8 B8 C8 D8 VI. Application for patents (alkyl-2- (N, N-di substituted amino) alkanol alkanoate), Yaohui Day i- &quot; vr a salt And its mixture. '、 子 上 了 接 15 1 · For example, the method referred to in item 1 of the patent scope, wherein the penetration enhancer is 2- (N, N-dimethylamino) propionic acid dodecyl ester Hydrochloric acid (dodecyl 2- (N, N-dimethylamino) -proprionate ^ hydrochloride) 〇1 6 · As the method in the scope of the application for the patent claims, the cold in the beans Contains at least one aliphatic U to the class of the Chinese parent month, said Euro 1 7 · The method as described in item 1 of the scope of the patent application, wherein the lipophilic ingredient contains at least one glyceride selected from the following group, including: monoglycerol Esters (monoglycerides), such as diglycerides, tri lri and mixtures thereof. ^ (Please read the notes on the back before filling out this page) I 37 &lt; &lt; Zhongqule its family 00, next on "method with m Λ head 1 fine · (Fang Zi y You-ί choice ^^ &gt; Called similar to Λ, a nutritional item, one gallery, one salt.} The third acid in, Wai one oil len) Fan Shaodan 10ti Li Zhiji Tris special oil cyr Please include Gan Jing im Application: oil tr If printed by the Consumers Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs of the Ministry of Economic Affairs of the People's Republic of China, the basic and acidic acid will be moderated in the 4th, 7th, and 7th method. The first category is a special group of profitable confession, which is specifically requested to apply for a value of 0: 0 · As described in the first patent application, the acidic system provides a range of about A buffered acid value of 3 to about 6.5 is given to the claimed composition. Wuhe Bao group, the group of esters and their family anhydrides, the lower alcohol method is called the sugar recipe from the pear selection mountain, the ethene agent is ethylated 87 1 milk oxygen the first poly Wai I, r containing saponin-like esters Step sugar, please apply for one cane ... 200407149 The scope of patent applications (polyoxyethylene sor |) tan esters); long chain alcohols (long chain alcohols), and glycerol s. T, 2 2 · The method as claimed in item 1 of the scope of the patent application, wherein the emulsifier comprises at least one glyceride, selected from the following groups, including the above: 'glyceryl mOOnate Triolein, Triolein, JLri (M ^ Lstin), Tristearin, and mixtures thereof. / u 2 to reach its reach, the amount of the approximate calculation method Λ 01 Weigh the total rt items my 1 in C The group of alcohol is enclosed in a thin range containing Niangli Baojin Special steps please apply for one, such as More Printed by the Consumers' Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs 2 4.,! Please refer to item i in the scope to further include a preservative. Electricity, electricity, and food 2 5U Please refer to the method mentioned in item 1 above, and Lizhong Group further includes a local anesthetic. / 、 T 、、 和 口 妆 2 6 · As the “Ganshi” mentioned in item 1 of the scope of the patent application, 仏 仏 further contains a spice. Zhi Fang, where the composition 2 7 · as described in the scope of the patent application No. 3 ^ 1 is packaged in a single dose, and the method ^ 'in the forefront ^' f each composition of about 0.1 mg to The amount of gland 5 gas &amp; is 2 8 • Taituo as mentioned in item 3 of the scope of patent application is packaged in a single dose, and the forefront method ”wherein the composition is about every single dose. · The amount of milligrams to about% glandular dioxin is 2 9 · For example, please refer to item 3 of the patent scope: Dan You method, wherein the composition is about 0.001% by weight to about 1% by weight, about 0 · 5% by weight to about 1 q% prostaglandin E1 based on heavy lips) Dodecyl propionate propionate hydrochloride; 2-(N, N-dimethyl "II _____ 88 | ------ --r ------------------------ 'A—— This paper size is applicable to China National Standard (CNS) A4 (210X297) 'Benefit range 0 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs, spoon, spoon, 0.5% weight ~ about 0.5% food :, i T to about 10% weight ratio of ethanol; hurate); Libby to Approximately 10% by weight of ethyl laurate (ethyl weight): / gum, all r ;, from $ to about 5% by weight of artificial semi-synthetic melons, and the total weight of the compound is based on calculation. For erectile dysfunction in right patients, such as 'diabetes in two or more disease situations' is a treatment method for disease dysfunction, which includes a semi-identifiable number of steps ^ scaphoid fossa placing an erection to induce a scintillation / "lj Prostaglandin E 1 composition, comprising: a shear J If; a sugar gum and a polymerized thickener, selected from the group consisting of one acrylic polymer, = #acrylic polymer; Cl to alcohol “Class” —from the following ethnic groups, including: a mixed character of fatty daggers, aliphatic C8 to C3. Esters, and one-one-acid “slow” • an uncle with a patient Polysaccharides with high blood pressure that say more than one kind of disease situation! Self-contained-; a group of polyacrylic polymers This component is selected from the following ethnic groups, including '· an acidic buffer system. Please read the precautions in the back first and then fill in the Φ 3 2 number of steps in the method. ; Set 1 E disease, &gt; pits on the top, pits on the glands, glands-like obstacles &amp; boat, agent two &quot; month's words strong and active body plus thinning and solid changes to Pap V For semi-osmotic cuts, use it for each individual, one for each agent, thickening polymer 89, the diseased hair is dirty, and the package is included.-Included in the booklet I Ψ 2 200407149 Groups containing group-like esters, 30 f group U group 8J gathered C. The acid is selected from the family and dilute from the lipid series. One is to slow down the number of members. The physical properties and group 8S-synthetic acid gums .. One C mixed with one tree &quot; one to one sugar C1 Multi-family it 1 ^ — · m 0 3 The diseased hair group is mutated into 511 physical properties. # The original contains the incision and the compound is mixed with acid. Then, each glue is mixed with each other. The tree is wide, the sugar 4 is C1, and it is cut into a multi-family. It has a disease that contains half a half of r. The polyene is from U ^ species: the amount should not be oxidized. For the 4 strong gatherings, one is to add the number of dilute parts i; the glandular column is set to 1 to treat the fossa glandular shape of the pre-treatment radiotherapy j Qingju Zhou Yin, pre-disorder disease &amp; The f energy body is sturdy and healthy. The last one contains J and the package;:, contains the group selection group package SI, 5 3 agent groups, the condensed group 8 ^ under the polymerization of the C acid Family (please read the notes on the back ^ before filling out this page) I ----- II- Group 3 4 Scope Item 3 3 The method mentioned above, the administration of the complex ganglioside Ει composition is at least One f "zhong semi-solid" main friend twice. 3 5 · As mentioned in item 33 of the scope of the patent application, the administration of the composition of the prostaglandin Eilat composition is referred to as the standard employee consumer cooperative of the Ministry of Economic Affairs of the Middle and the Middle Regions. 3 6 3 The method referred to in item 3, the administration of the f ^ body prostaglandin E1 composition is daily-times, mid-solid This paper size applies the Chinese National Standard (CNS) A4 specification (21〇 &gt; &lt; 297 mm) 200407149 A8 B8 C8 D8 Patent application scope a A component, selected from the following ethnic groups' contained to C8 alcohols, a Aliphatic C8 · to. 3. A mixture of vinegar daggers; and, a painful acidic buffer system. A fat and a double connection can include burning Ν, and enclosing one (N ~ (Science, a -2 group, a base pharmacological acid, burning a lower alkanoic acid, and alkane I salt from Λ chain, Acid-selected Λ salt alkane, amino acid chain agent ammonium alcohol; Strongly substituted alkane plus alcohol to be taken through i i The first ~ 2 generations of basic alkanoyl Y ammonium are used for salt. The second generation was used by 8 3 to use: i P ^ from the group C, C acid therapy, heart depression, and the selected group of the treatment group Yu Yuzhi, T, The composition of the enzymes used in the lipids is the same as that of the lipid enzymes, which hinders the synthesis of lipids in the blood. The barriers are high and the polymerization is negative. The energy, acid, and acid esters are 511. 4 mixtures of urinary dysfunction, C and C mixed drugs, sugar can be gathered together to the right one. The C1s are one person or within 1 family, it is prepared for the disease, and there are 0 tree sugar, more than 1 The condition of the fat-containing system is small, except for Θ Zhou Yi and the disease should be adapted to the situation: ,, the disease gland j person contains the systemic diseases, the disease-free package vinegar is the pre-treatment, 030 From the disease, the disease is placed to the slow. The disease is J # J. Matters to read the back of the note and then fill in this page) .0 - Order Lu - · Ministry of Economic Affairs Bureau of Standards Co-op staff printed a quasi-standard paper suitable home PCT a public 972