KR20010009489A - Liquid-type topical therapeutic agents for male sexual dysfunction and its process - Google Patents

Abstract

PURPOSE: A liquid-type topical therapeutic agent for male sexual dysfunction is provided which has stability and non-toxicity. Also, a preparation method thereof is provided. CONSTITUTION: A liquid-type topical therapeutic agent for male sexual dysfunction is prepared by the following steps of: (i)mixing 30-40 wt.% of Torilis Fructus, 20-30 wt.% of Epimedii Herba, 10-20 wt.% of Notoginseng Radix, 5-15 wt.% of Santali Lignum; (ii)after extracting the mixture with ethanol, filtrating the obtained extract; (iii)distilling the filtrate and mixing 5-10 volume% of Laurocapram thereto; (iv)after performing homogenation, manufacturing in spray type propellants.

Description

Liquid-type topical therapeutic agents for male sexual dysfunction and its process}

The present invention relates to a skin external male sexual dysfunction treatment and a method for manufacturing the same, more specifically, a skin external injection form containing a casualty, Eumyangkwa, samchil, cloves, fennel as the main ingredient herbal medicine and laurocapuram as a skin absorption enhancer The present invention relates to a herbal drug tin and a preparation method thereof.

Penile erection, spermatozoa, ejaculation, and extreme sensation have different mechanisms in male sexual activity, and in patients who complain of sexual dysfunction, they exhibit specific characteristics.Increased libido, erectile dysfunction, and ejaculation Ejaculatory dysfunction, Organization failure, etc. Most men do not realize that sexual dysfunction is a type of disease, and they often turn to energy and look for energy or aphrodisiac. However, it is obvious that sexual dysfunction is a disease, of which about 2 million men in Korea suffer from erectile dysfunction, and anyone who suffers from an increase in adult diseases such as diabetes, hypertension, stress, industrial accidents, drinking, smoking, etc. Because of this, the prevention and treatment of these diseases is very important.

Currently, the erectile dysfunction treatment agent is a prostaglandin E ₁ formulation, which is introduced by a US Upzon caverject, which is injected directly into the cavernous corpus cavernosum. Although it is effective in terms of effect, the administration method is an injection, and there are concerns about side effects such as avoiding injection and damage to penis tissue.

In addition, Bybus's muuse is a pellet-type suppository that delivers erection-inducing vasodilation to the corpus cavernosum directly through the urethra, which does not affect other areas. There is a sense of rejection in that it is put directly into the urethra, and it is known that the massage needs about 5 minutes after self-injection.

In addition, Pfizer's Viagra, a product introduced in the United States, is easy to take orally, but it is known that heart disease can cause heart attacks due to blood pressure drop.

In addition, there are a number of herbal preparations for treating male sexual dysfunction, including recently commercialized S-Cream, but there are no preparations that can simultaneously treat erectile dysfunction and premature ejaculation.

The purpose of the present invention is to have an excellent therapeutic effect against male sexual dysfunction, as well as raw materials known to be safe for the human body as possible, and by using a special skin absorption enhancer to maximize the absorption of the herbal ingredients in the treatment site drug effect By developing a spray-type treatment that shortens the time of effect expression as well as strengthening the effect, it has no side effects that existed in the conventional medicine treatment, and also has the effect that could not be expected in the herbal medicine (medicinal herbs) preparation, and made easier to use It is to provide a novel external skin treatment for male sexual dysfunction and a method of manufacturing the same.

1 is an experimental diagram for the corneal reflection inhibitory effect of the rabbit.

Figure 2 is a Doppler measurement picture of the blood flow rate of the corpus cavernosum arterial contractor before drug application.

Figure 3 is a Doppler measurement picture of the corpus cavernosum arterial contractor peak blood flow rate four days after drug application.

Figure 4 is a Doppler measurement picture for the peak blood flow rate of the corpus cavernosum arterial contractor 7 days after drug application.

Figure 5 is a photograph of the audiovisual stimulation penis erection (Rigiscan) after drug application.

Figure 6 shows the average ejaculation time after drug treatment.

The external skin treatment for male sexual dysfunction of the onset contains five kinds of herbal medicines of casualty, Yin-Yang, Samchil, cloves, and fennel, and laurocapuram, a skin absorption enhancer. It is a herbal drug containing 20-30% by weight, 10-20% by weight, 10-20% by weight of clove, 5-15% by weight of single flavour, and 5-10% by weight of laurocapram.

Hereinafter, a detailed description of each herbal component of the present invention will be described.

Torilis Fructus is a fruit of the biennial herb (Torilis japonica Decandolle), belonging to the family Obsidaceae (Umbelliferae). Ingredients include L-Pinene, Campen, and Isovaleric acid, which have antifungal, antiviral and antitrichomonas effects, and sex hormone-like and local anesthesia. It is a kind of herbal medicine that is known as a tonic tonic.

Epimedii Herba is a perennial herbaceous Epimedium grandiflorum MORR belonging to the Berberidaceae, harvested from summer to autumn and dried in the sun or shade. Ingredients include Icariin, des-o-Methylicariin, Magnoflorine, etc.It selectively expands blood vessels in the lower abdominal lumbar region and stimulates genital stimulation and blood pressure. It is a kind of herbal medicine that is known to have a lowering effect and an aphrodisiac effect.

Notchiinseng Radix is the root of Panax notoginseng (Bulk F.H. chen) belonging to the family Araliaceae. Ingredients include Sansitisaponin and Ginsenoside, which are used for bleeding due to hemostasis, and increase coronary blood flow and lower blood cholesterol. Coronary artery disease, hypertension, etc. It is a kind of herbal medicine that has been used for the treatment of medicine.

Clove (Caryophilli Flos, Clove) is a bud of the Cloves (Eugenia caryophyllata Thunberg) belonging to the family Myrtaceae. The vase is removed and dried in the sun. Ingredients include essential oils such as eugenol and flavonoids such as camperol and ramnetin.They have a dry stomach effect and are used for indigestion and acute gastroenteritis as a fragrant dry stomach medicine. Esau is a type of herbal medicine that is safe enough to be used for tooth decay and analgesic effect.

Santali Lignum album is a heartwood of the wood of the alpine tree (Santalum album Linne), an evergreen tree belonging to the family Santalaceae. Cut short and remove sapwood. 3 ~ 5% of essential oil is contained in core material, and the most essential component of alpha, beta-santalol (α, β-Santalol) (90% or more), which is classified as terpenoid alcohol And other pigment components such as Santalin. This is a kind of herbal medicine that has a strong urinary preservative effect and is used as a urinary tract preservative and is known to reduce skin sensitivity.

Laurocapram (Laurocapram) is known to have an excellent effect of promoting the absorption of the drug when applied to the skin along with the drug is a safe skin absorption enhancer widely used in external preparations such as cosmetics.

In addition, the manufacturing method of the external skin male sexual dysfunction treatment agent of the present invention is 30 to 40% by weight of the casualty, 20-30% by weight of the Yin Yang Guk, 10-20% by weight, clove 10-20% by weight, 5-15% by weight of fennel After mixing in the blending ratio, the active ingredient is extracted using ethanol as an extractant, the obtained extract is filtered, and the obtained filtrate is distilled again, and then 5-10% by volume of lauroccapram is used as a skin absorption enhancer. It is summarized as a preparation method of the herbal drug tin, characterized in that it is formulated into a spray in the form of a spray.

In order to select the herbal medicines constituting the present invention, a pharmacological test was conducted as follows.

(next)

I. Effects on the Relaxation Response of Rabbit Penile Cavernous Smooth Muscle

1. Material

1) Sample: Group 1-Casualties, Yin Yang Kwak

Group 2-Casualties, Yin Yang Kwak, Sam Chil

Group 3-Casualties, Yin Yang Kwak, Sam Chil + Lauro Capram

Group 4-Casualties, Yin Yang Kwak, Samchil + Cloves, Danyang + Laurocapram

2) Experimental animals: New Zealand white male rabbit weighing 2.5-3 kg

20 horses

3) Appliances and Appliances:

end. Force transducer

I. Physiography (Biopac systems, Santa Barbara, California, USA)

All. Organ chamber

la. Tyrode solution: Composition ^{- Na + 153.6 mEq / L,} K + 5.3 mEq / L, Ca ++ 3.0 mEq / L, Mg ++ 1.2 mEq / L, Cl - 157.2 mEq / L, H 2 PO4 - 0.6 mEq / L ^{_{, SO 4 - 1.2 mEq / L}} , HCO 3 - 7.1 mEq / L, glucose 11.4 mEq / L

hemp. Universal stand, Air pump

bar. microscope

four. Surgical Scissors, Surgical Tweezers

Ah. Syringe, thermometer, thread, beaker

character. Animal Cages, Animal Fixtures

car. Norepinephrine, Relaxant (Acetylcholine)

2. Experimental method

1) New Zealand white male rabbits weighing 2.5-3 Kg were reared at a temperature of 23 ± 1 ° C, a relative humidity of 55 ± 5%, and a contrast shift of 12 hours.

2) Water and feed were supplied for free intake.

3) Put the rabbit on the stand and fix the limbs and head.

4) Inject rabbits with Pentobarbital Sodium (30-50 mg / kg) and let them die before carotid artery resection and blood loss.

5) Remove the penis and immediately store it in HEPES buffered Tyroide solution at 37 ~ 38 ℃ to prevent autolysis.

6) Prepare smooth muscle sections (6 mm × 2 mm × 2 mm) of the corpus cavernosum using a microscope.

7) Hang the fixed corpus cavernosum smooth muscle section with thread and transfer to 10 ml of organ chamber.

8) Fill the Organ chamber with HEPES buffered Tyroide solution at 37 ~ 38 ℃ and soak in 37 ℃ hot water bath while supplying 95% oxygen and 5% carbon dioxide gas.

9) Connect force transducer and physiography to corpus cavernosum smooth muscle section.

10) After adding contraction agent (Norepinephrine) artificially contraction and confirm that the relaxation reaction to the relaxant (Acetylcholine) is observed, confirm that there is no damage of the corpus cavernosum and proceed with the experiment.

11) Relaxation Effect Measurement:

end. Contractors are added to the corpus cavernosum smooth muscle and contracted.

I. When the tension in the state of shrinkage with a shrinkage agent is 100, it is measured how many percent the tension is reduced.

3. Experimental results:

1) The relaxation effects on the cavernous smooth muscle in each group are shown in Table 1.

Table 1

Relaxation effect on the cavernous smooth muscle of each group

Group 1 Group 2 Group 3 4th group Shrinkage inhibition (%) 41.7 ± 11.5 33.6 ± 17.12 18.4 ± 15.92 16.9 ± 19.3 Relaxation effect (%) 58.3 ± 11.5 66.4 ± 17.12 81.6 ± 15.92 83.1 ± 19.3

2) As a result of the test, 58.3% of the group 1 of the casualties and Yin-Yang Kwak group and 66.4% of the group 2 of the casualties, Yin-Yang Kwak, and Samchil were effective in erectile dysfunction.

3) In the case of group 3, which contains laurocapuram in the prescription of group 2, the effect is rapidly increased to 81.6%, and the drug effect is maximized by the addition of absorption enhancer.

4) In group 4, clove and fennel were added to 83.1%, which showed no effect on relaxation effect on corpus cavernosum smooth muscle.

II. Effect of Surface Corneal Sensitivity Using Rabbit Cornea

1. Material

1) Sample: A-Clove, unidirectional

B-Cloves, Unicorns + Casualties

C-Cloves, Unicorns + Casualties + Laurocapuram

D-Cloves, Unisons + Casualties, Yin Yang, Samchil + Laurocapuram

E-control (2% Lidocaine solution)

2) Experimental animals: 20 rabbits with weight 2.0 ± 0.8 Kg regardless of male or female, without eye disease and showing normal corneal reflection.

3) Appliances and Appliances:

end. Mandarin

I. Pin-prick

All. gauge needle

la. Animal cages

2. Experimental method

1) Twenty rabbits with body weight of 2.0 ± 0.8 Kg without eye disease and showing normal corneal reflection were bred at a temperature of 23 ± 1 ℃, a relative humidity of 55 ± 5%, and a contrast shift of 12 hours.

2) Water and feed were supplied for free intake.

3) Twenty rabbits were randomly divided into five groups and each group of drugs A, B, C, D, and E were applied to the cornea.

4) The drug was applied to the corneal capsule by 0.1 ml (3 drops) of each test drug using a 24 gauge needle, and the eyes were closed for 1 minute to prevent the drug from spilling.

5) In the corneal perception test, the rabbits were stabilized indoors away from direct sunlight, and the corneal stimulation was induced by prick corneal stimulation using a 24 guage needle inserted with mandarin. It was performed for a minute.

6) In every 5 minutes, the corneal perception test was repeated six times. If the corneal reflection did not appear in one pin-prick stimulus, it was regarded as sensory deterioration. Was regarded as a complete local sensory deterioration.

3. Data Analysis:

In the pin-prick corneal perception test performed every 5 minutes, the local sensory effect of suppressing corneal reflex was evaluated and averaged. Results were analyzed by paired t test and statistically significant when p value was less than 0.05.

4. Experimental results:

1) The corneal reflection inhibition effect of the rabbit in each group is shown in FIG.

2) The results of corneal perception after the application of Lidocaine showed that corneal reflex was inhibited from 5 minutes after application, and the pin-prick corneal reflex intensity was 5.83 ± 0.52 points, and the reaction was maintained for 10 minutes and then decreased.

3) Inhibition of corneal reflex by prescription of group A and group B occurred 10 minutes after application, and the intensity was 3.8 ± 0.68 and 4.9 ± 0.36, respectively, and the effect lasted more than 30 minutes, but the 30 minutes Over time, a decrease in the effect was observed.

4) In the case of group C with laurocapuram, a skin absorption enhancer, corneal reflection inhibition was already observed at 5 minutes of application. The intensity was 5.77 ± 0.41 points and the duration was 30 minutes or more. Due to the shortening of the drug expression time, the phenomenon of maximizing drug effect was clearly observed.

5) The effect of group D was not significantly different from that of group C, so Yin-yang and Samchil did not show any significant effect on the corneal reflex effect of rabbits.

6) All rabbits treated with drug in each group did not cause hyperemia, erythema, edema and unusual lesions for up to 48 hours in the cornea, iris and conjunctiva.

That is, as a result of the above experiments, it can be seen that the casualty, Eumyangkwa, Samchil, cloves, fennel, laurocafuram compound of the penile corpus cavernosum relaxation effect and penis glans somatosensory potential suppression effect is increased, erectile dysfunction and It was possible to achieve the present invention that can simultaneously treat premature ejaculation.

Furthermore, if the casualty, Yin-Yang, and Samchil are less than 30%, 20%, and 10% by weight, the therapeutic effect on erectile dysfunction is questioned. Will be affected. If clove and fennel are 10% by weight or less than 5% by weight, the therapeutic effect of premature ejaculation is questioned.If the clove is 20% by weight or more, the anesthetic effect is severe, rather it negatively affects the treatment. If it gives off discomfort due to its peculiarity. In addition, if laurocapuram is less than 5%, there is almost no skin absorption promoting effect, and if it exceeds 10%, side effects are concerned.

Therefore, the present invention has the advantages of providing a composition for treating external skin male sexual dysfunction and a method for producing the same.

External skin male sexual dysfunction treatment agent of the present invention in a container designed to spray the herbal drug tin liquid prepared as described above in a spray form of 3 to 5 ml per bottle, for the purpose of sexual intercourse 5 to 10 minutes before sexual intercourse And 2 to 3 times in the glans, and for the purpose of treatment, 3 or more times per day for 3 weeks or more.

The external dermal male sexual dysfunction treatment agent according to the present invention is introduced in the composition and manufacturing method of the modern scientific principles, the results and scientific results of pharmacological experiments on animals and clinical trials on human results, erectile dysfunction Effectiveness of 89% and premature ejaculation of 90% proved to be an effective treatment.

On the other hand, in the acute oral toxicity test of rats of the present invention, no unusual abnormalities were observed in clinical symptoms, weight change and autopsy findings.

Hereinafter, to prepare examples and experimental examples of the present invention.

(Manufacture example 1)

1. Drug substance volume

In 100 ml

Main ingredient casualty (raw) 35 grams

Main ingredient Yin Yang Guk (Saenggyue) 25 grams

Active ingredient three seven (raw) 15 grams

Active Ingredient Clove (Pharmacopoeia) 15 Grams

Active ingredient Sandalwood (raw) 10 grams

Skin absorption enhancer Raurocapuram (Special) 10 milliliter

Leaching Agent Ethanol (Pharmacopoeia) Proper

2. Manufacturing Method (1)

1) Remove raw materials or mixed substances and other foreign substances by carefully selecting raw materials such as casualties, Eumyangkwa, Samchil, cloves, and single fragrances. Casualties, Yin Yang Guk, and Samchil are in daylight or 60 ° C or less, and the essential oils such as cloves and scents are air dried at the lowest possible temperature so that the essential oils do not volatilize. Fragment it as much as possible to get bigger.

2) Take 35 grams of pre-treated casualties, 25 grams of Eumyang, 25 grams, 15 grams, 15 grams of cloves, 10 grams of clove, add about 500 ml of ethanol, seal the container, and stir at room temperature for 15 days. The soluble components were leached out of the solution and filtered through anhydrous to obtain about 400 ml.

3) Add 60 ml of ethanol to the residue, wash, compress, and combine the above leachate with the washed solution to obtain about 450 ml of herbal tincture.

4) The crude herbal tin liquid treated as described above is put into a recovery apparatus and distilled to obtain about 90 ml of the stock solution.

5) Add 10 ml of laurocapuram to the stock solution obtained above, and homogenize to make 100 ml final stock solution.

3. Manufacturing Method (2)

The final crude solution prepared by homogenizing as in the preparation method (1) is divided into 3 to 5 ml per bottle in a container designed to be sprayable.

Experimental Example 1

Formulation

The results of testing the components and quality standards of the external skin male sexual dysfunction treatment agent prepared according to Preparation Example 1 were as follows.

A. Appearance: Pale yellow clear and transparent herbal tincture with unusual fragrance

N. Confirmation: When tested according to the General Test Method of the Korea Food & Drug Administration, casualties, Yin Yang Kwak, Samchil, Cloves, and Danyang were identified.

C. Content of eugenol in cloves: at least 5 mg per 100 ml

D. pH: 4.0-5.0

M. Methanol: No detectable value when tested according to the Korean Pharmacopoeia General Test Methods.

Iii. Ketone, isopropanol and tert-butanol: were not detected when tested according to the Korean Pharmacopoeia General Test Methods.

G. Heavy metals: 30 ppm or less

Experimental Example 2 (stability test)

As a result of conducting a test on the items described in Experiment 1 for the skin external male sexual dysfunction treatment prepared according to Preparation Example 1, the stability of the formulation was guaranteed for 18 months or more. In particular, as a result of the test of the content of eugenol in the cloves, all of the long-term preservation test was confirmed to pass the product within the standard.

Table 2

Experimental Example 3 (Clinical)

Clinical trials for erectile dysfunction and premature ejaculation were conducted. The results are as follows.

[Clinical trial for treatment of erectile dysfunction of the present invention]

Introduction

Erectile dysfunction (referred to as "ED") refers to a condition in which it is difficult to cause and maintain an erection suitable for sexual intercourse because the cavernous internal pressure is not elevated or maintained for a variety of reasons. It is estimated that about 10% of adult men over 20 years old have erectile dysfunction. Such treatments for erectile dysfunction include surgical treatments such as penile implants, or oral treatments such as vasodilators, holmones, and viagra, which are injected directly into the corpus cavernosum, but surgery is expensive. In other words, once the procedure, the existing natural erectile power is impossible to restore the original, and other holonic agents, including injections and various oral treatments have severe side effects and could not be successfully used to solve problems caused by erectile dysfunction. Therefore, the present inventors searched the literature to find a new treatment method for erectile dysfunction, and examined the slurs described in the ancient Chinese medicine book and extracted the active drug ingredients from the herbal medicines such as Yin-Yang and Samchil by a special manufacturing method to make the present invention. The effect was studied.

2. Target and Method

1) Subjects: Thirty patients aged 18 years or older who agreed to the trial clinical treatment who were admitted to OO hospital were included in this study.

Table 3

Patient characteristics

Characteristics Placebo Treatment No. of Patients 15 15 Patient age (Year) Mean 51 50 Range 20-69 23-70 Etiology Organic 10 11 Psychogenic 2 2 Mixed 3 2 Duration of ED (Year) Mean 3.2 2.9 Range 0.4-20 0.5-11 Med Hx (%) Hypertension 31 29 Diabetes 10 7.8 Prostatectomy 19 18 Depression 5.1 6.5 IHD 9 12

(2) Age: The mean age of the patients was 51 years (20-69 years), 10 patients with organic erectile dysfunction, 2 patients with psychogenic erectile dysfunction, and 3 patients with mixed erectile dysfunction.

2) Test method: After spraying the present invention in the form of external skin spray evenly over 2-3 times of genitals, it was recommended to have sexual activity twice a week within 5-10 minutes thereafter.

(1) objective inspection

A) Determination of systolic maximum blood flow rate of corpus cavernosum artery-Use the Color Doppler to compare the peak blood flow rate before and after drug application twice a day, 4 or 7 days.

B) Audio-visual stimulation penis erection reaction: Rigiscan was used to compare the audio-visual stimulation penis erection (maximum erectile stiffness) with drug application twice a day and 7 days after drug application.

(2) Subjective Assessment:

Twice a day, one month after the drug application, sexual intercourse, the degree of improvement in erection is surveyed using the International Penis Erectile Function.

The measure of effectiveness was in response to IIEF questions 3 and 4, which assessed the number of insertions and erection duration of the subject.

3) Statistical treatment: Mainland-Gart analysis using Fisher test and Altham method.

3. Test result

(1) objective inspection

A, Doppler measurement results before and after drug application are as shown in Figs. 2, 3 and 4, and the maximum blood flow rate of the cavernous artery systolic system before and after the drug administration was shown. The average speed was 7 cm / sec and 8 cm / sec, respectively, but after the drug administration of the present invention, the average increase was 10 cm / sec and 15 cm / sec, respectively. See Table 4)

Table 4

Cavernous Artery of the Right Penis Cavernous Artery of the Left Penis Before application 7 cm / sec 8 cm / sec After application 10 cm / sec 15 cm / sec

B) Audio-visual stimulation of the penile erection (maximum erectile stiffness) before and after drug application showed that the erectile stiffness of the distal penis and the base of the penis before the drug application averaged 60% 2 minutes and 80% 3 minutes, respectively. Significant improvement was observed in erectile dysfunction with an average improvement of 60% over 5 minutes and 80% over 10 minutes after application of the drug of the invention, respectively. (See Figure 5)

(2) Subjective Assessment:

Table 5 shows the average scores of the subjects who responded to IIEF Question 3 regarding the number of insertions at the end of the dosing and IIEF Question 4 about the insertion duration. (5 is out of 5, the lowest value is 1 and the highest value is 5. If no sexual intercourse is attempted, 0 is treated.)

As can be seen in Table 5, the present invention was effective in the treatment of erectile dysfunction. Overall, the proportion of subjects who thought that medication to improve erection was effective was 89 percent in the treatment group receiving the disease, compared to only about 15 percent of the placebo.

Table 5

Evaluation of IIEF Questions 3 and 4

Placebo group Treatment group P How often were you able to penetrate your patner? BaselineWeek 4 1.92.2 1.93.6 <0.0001 How often were you able to maintain your erection after penetration? BaselineWeek 4 1.62.1 1.63.5 <0.0001

[Clinical Study on the Treatment of Premature Ejaculation of the Invention]

Introduction

Premature ejaculation (hereinafter referred to as "PE") is the phenomenon of ejaculation immediately before or immediately after intercalation of the penis during sexual intercourse or inability to control ejaculation for sufficient time to satisfy oneself and the other party for more than half of the sexual intercourse. , The most common form of ejaculatory disorder, accounting for 60-70% of sexual dysfunction As a treatment for premature ejaculation, there are psychotherapy and drug therapy. However, psychotherapy requires too long-term effort, and there are many fears of failure or recurrence. Drugs for this purpose include psychotropic drugs that suppress the excitability of the central nervous system, preparations for local anesthesia or vascular agents for the slowing of the peripheral nervous system, but in the case of central nervous system inhibitors, sexual activity is not possible due to loss of sexual desire. Local anesthetics, such as lidocaine ointment, may cause erectile dysfunction due to vasodilation, short durations, and need to be used immediately before sexual activity, and vasodilators such as nitroglycerin may cause headaches. The side effects were severe and could not be used successfully in solving problems caused by premature ejaculation. Therefore, the present inventors searched the literature to find a new treatment method for premature ejaculation, and then reviewed the slurs described in the ancient Chinese medicine book and extracted the active drug ingredients from the herbal medicines such as casualties and cloves in a special manufacturing method to make the present invention. Was studied.

2. Target and Method

1) Subjects: Fifty patients with premature ejaculation and 20 patients with premature ejaculation with premature ejaculation who participated in the clinical trial were enrolled. (See Table 6)

(1) Diagnosis: The mean duration of premature ejaculation symptoms was 11.3 years (1-30 years), and the onset of symptoms was more than 80% (49 patients) of primary premature ejaculation patients with pneumonia. Eight patients from the beginning of marriage and three patients with premature ejaculation began. The prevalence of premature ejaculation was found in 10 patients who had ejaculation before or after vaginal insertion, 37 patients who ejaculated in 1 minute, 9 patients ejaculated in 2 minutes, and 4 patients ejaculated in 3 minutes. The spouse's satisfaction with sexual activity was very low at an average of 12.5% (5-25%).

Table 6

Patient characteristics

Characteristics Pure PE PI PE ^* No. of Patients 30 20 Patient age (Year) 39 (24-49) 42 (31-57) Partner age (Year) 35.4 (22-46) 27.8 (30-53) Duration of marriage (Year) 11 (0.5-26) 16 (1-33) Duration of PE (Year) 11.0 (1-27) 11.6 (2-30) Ejaculation time (minute) 1.54 1.33 PSP ^** (%) 15.4 9.6

* PI PE: Psychogenic Impotence PE

** PSP: Partner satisfactory percentage

(2) Age: The average marriage duration was 13.5 years (0.5-33 years) for married persons, and the average age of patients was 35.5 years (24-57 years) and the average age of spouses was 32.6 years (22-53 years). .

(3) Examination: All patients with premature ejaculation did not have a specific history or disease of the nervous system in the physical examination, and they were excluded from urological diseases such as urinary tract infection or chronic prostatitis. The test was a normal category.

(4) Other drug use experience: Twenty two patients (37%) had experience using various local anesthetics or herbal medicines and only one of them was effective.

2) Test Method: After spraying the present invention in the form of skin external injection into the genitals 2-3 times, it was recommended to have sexual activity twice a week within 5-10 minutes thereafter. The ability to control ejaculation was examined weekly. The assessment of assessment control ability allowed the patient to self-evaluate the time between the insertion of the penis into the vagina after the onset of sexual activity and the ejaculation time (hereinafter referred to as ejaculation time) and marital satisfaction. In addition, during the observation period, special side effects, hypersensitivity reactions, and dermatitis were observed in detail. Results were analyzed using 4 weeks of treatment as a treatment unit and 3 months after treatment, the presence of premature ejaculation was observed by telephone.

3) Statistical treatment: In the pre- and post-treatment clinical studies, the change of ejaculation time was tested by Chi-square test using the SPSS program of IBM computer, and the p-value less than 0.05 was determined to be statistically significant. .

3. Test result

The mean ejaculation time increased from 1 minute before treatment to 9 minutes after 1 week, 12 minutes after 2 weeks, 14 minutes after 3 weeks, and 15 minutes after 4 weeks. In 19 (95%) 20 patients with premature ejaculation with increased ejaculation time of 8 minutes or more, the present invention was found to have a better effect in patients with premature ejaculation with erectile dysfunction. Total efficiency was found to be 90% (see Figure 6).

* Typical case 1

YangXX, male, 57 years old, ○○ city police officer

Eleven years ago, he had poor sex, had premature ejaculation, and had sexual intercourse. I have been treated at the present ○○ hospital and other prominent medical centers, but it did not work. The sexual intercourse time was about 1 minute, and ejaculation prematurely after penis insertion prevented my wife from being satisfied with her sex life. For this reason, there were frequent marital conflicts. However, after one week of using this product, symptoms improved and the function partially recovered. Sexual intercourse was extended to 10-15 minutes, and after a month of continuous use of this drug, sexual life was restored.

* Typical Case 2.

Mr. JinXX. Male, 54 years old, ○○ City Suhyup executive

As I grew older, my sexual desires declined, and it was difficult to succeed in sexual intercourse once a month. If the penis touches the penis during intercourse, it ejaculates immediately and has been very complained by his wife. One month after using the present invention, a satisfactory sex life was achieved, and the intercourse time was extended. After three months, the couple's life returned to normal.

* Typical case 3

Mr. XX. Male, 27 years old ○○ City confectionery worker

A couple of years ago, there was a sexual problem between the couple, which could not satisfy the wife's sexual desire. Intercourse time was about 1 minute when inserted ejaculate immediately. Several herb medicines were taken but did not have much effect. However, after using the present invention five times, the effect was obvious and was able to lead a successful married life. After 1 month of continuous use, sexual intercourse extended to more than 30 minutes and sexual activity returned to normal.

* Typical case 4

Mr. XX, male, 43 years old, ○○ city plastic factory executive

Nine years ago, sexual life was not satisfactory, and premature ejaculation was present. ○○ I received treatment at a famous hospital, but it did not work. After the introduction of the present invention for half a month, premature ejaculation is significantly improved. After several months of continuous use, sexual life returned to normal.

* Typical case 5

Jeung, XX, male, 42 years old, ○○ prefecture brick factory employee

The couple's life was not satisfactory because of premature ejaculation. Intercourse time was less than 1 minute and ejaculation occurred immediately after insertion. He had a great burden and was attempting to treat it with the middle ○ medicine in the present ○○ hospital, but it was ineffective. After using the present invention for half a month, the couple's life became better, and premature ejaculation improved. The patient himself said that he had "obtained the right to love." Recently, couple life has been restored to normal.

Experimental Example 4

Local toxicity

1. Skin irritation test on rabbits of the present invention

1) Test Method:

end. Test animals should use young and healthy white rabbits (2.0-3.0 Kg).

I. At least six test animals should be used. Place controls as needed.

All. The dosage is 0.5 ml if the test substance is a liquid.

la. The application area is the skin of the back of the hair, and it is composed of two parts of the skin and skin of 2.5 cm × 2.5 cm.

hemp. The method of application is to apply the test substance to the skin 2.5 cm wide, cover it with gauze, and fix the gauze with tape. To prevent evaporation of the test substance on the gauze, cover it with a solid, inert, non-reactive solid foil and secure it with tape.

bar. Observation of the site is performed 24 and 72 hours after the administration of the test substance and evaluated according to Table 7.

Table 7

Evaluation of Skin Response

(1) erythema and skin formation

No erythema 0 Very light erythema (only visible to the naked eye) One Clear erythema 2 Slightly severe erythema 3 Severe erythema (blush redness) and mild peel 4 Total possible erythema score 4

(2) edema formation

No edema 0 Very mild edema (only visible to the naked eye) One Mild edema (if the swelling is distinct and the margins are clearly distinguished) 2 Normal edema (when swelling about 1 mm) 3 Severe edema (swelling more than 1 mm and extending beyond the exposed area) 4 Total possible edema score 4

2) Results:

When the present invention was closely adhered to the skin of rabbits, there was no change in general clinical symptoms and body weight. The skin reaction was visually evaluated during irrigation and irritation of skin and abrasions. No edema, no edema, etc., and a primary irritation index of 1.7 was evaluated as a product with little irritation.

2. Ocular Membrane Stimulation Test on Rabbits of the Invention

1) Test method

end. Test animals are young and healthy white rabbit (2.0-3.0 Kg).

I. Both eyes of the test animal should be examined 24 hours before the start of the test to ensure that there is no damage to the cornea such as eye damage.

All. The eye drop should be 0.1 ml if liquid.

la. The test substance is applied to one eye of nine rabbits, three of which are washed for 20 minutes after 20-30 seconds with 20 ml of sterile physiological saline solution in both eyes, and the other six are not.

hemp. Observations were made on the other eye, in which no test substance was administered, and the test substance was administered 1, 2, 3, 3, 7 days after the administration of the test substance and evaluated according to Table 8, and thereafter, if the injury remained, the interval was 3 days. Administration is carried out for at least 13 days.

Table 8

Grade of eye lesion

(1) cornea: A × B × 5 max. = 80

(A) cloudiness: the degree of thickening of the eye (observing the thickest spots)

No purging or turbidity 0 · Turbidity is dispersed or dense (unlike slightly slightly normal transparency) The tip of the iris is clearly observed One Translucent parts are easily observed, the tip of the iris is slightly unclear 2 Pearl color, end of iris not observed, pupil size observed 3 Iris is not observed due to opacity and cloudiness of the cornea 4

(B) the range of clouded cornea

Less than 1/4 (but not 0) One 1/4 or more but less than 1/2 2 1/4 or more but less than 3/4 3 1/4 to 1 4

(2) Iris: A × 5 maximum = 10

(A) grade

·normal 0 Significant wrinkle formation, hyperemia, swelling, moderate hyperemia around the cornea, singly or mixed, such as abnormalities, iris reacts to light (dull response is positive) One No reaction to light, bleeding, mostly destruction (some or all of the above symptoms) 2

(3) conjunctiva: (A + B + C) × 2

(A) redness (only for bleeding conjunctiva and eye conjunctiva, except cornea and iris)

Blood vessels are normal 0 Some blood vessels are clearly hyperemia One Wide crimson hue, each vessel not easily observed 2 Light cerise 3

(B) conjunctival edema

Not swell 0 Slightly swollen than normal One Significant swelling with partial abduction of the eyelids 2 Swelling of the eyelids about half of your eyes 3 Swelling of the eyelids to close more than half of the eye 4

(C) emissions

No discharge 0 Some emissions (except for small amounts observed in the inner tails of normal animals) One Emissions that wet the eyebrows and eyelids 2 Emissions that wet the periphery of the eyes, eyelashes and eyelids 3

2) Results:

As a result of the weight measurement, there was no change due to the present invention, and after the general symptoms were observed, there was no change in the general symptoms and death of the animals until the eye was restored to normal. The indices were in the range of 0 to 1, respectively, indicating that they belonged to the no play category.

In view of the above Experimental Examples 1, 2, 3 and 4, the external dermal male sexual dysfunction treatment agent according to the present invention is excellent in stability in terms of formulation, safe without toxicity and effective in male sexual dysfunction such as erectile dysfunction, premature ejaculation, etc. The therapeutic effect has been demonstrated.

Therefore, the present invention is an industrially excellent invention, the external dermal male sexual dysfunction treatment agent of the present invention is noteworthy.

Claims (3)

It consists of a ratio of 30 to 40% by weight of casualties, 20 to 30% by weight of Yin Yang Guk, 10 to 20% by weight, clove 10 to 20% by weight, 5 to 15% by weight of fennel and 5 to 10% by volume of laurocapuram. The composition of the external skin male sexual dysfunction treatment agent. The skin composition according to claim 1, wherein the composition ratio is composed of 35% by weight of casualties, 25% by weight of Yin Yang Guk, 15% by weight of samchil, 15% by weight of cloves, 10% by weight of fennel and 10% by volume of laurocapuram. Compositions for the treatment of male sexual dysfunction. 30-40% by weight of pretreated casualties, 20-30% by weight of Yin Yang Guk, 10-20% by weight of Samchil, 10-20% by weight of cloves, 5-15% by weight of fennel, mixed with ethanol, and then obtained Filtration of the extract and distillation of the filtrate, followed by homogenization of 5-10% by volume of laurocapram with a skin absorption enhancer, homogenization and preparation of a male external sexual dysfunction treatment, characterized in that it is formulated as a spray injector. Way.