CN114533658A

CN114533658A - Composition for treating premature ejaculation by SS-PE and preparation method thereof

Info

Publication number: CN114533658A
Application number: CN202210209352.2A
Authority: CN
Inventors: 郭建芳; 杨圣吉; 任震; 赵庆霞
Original assignee: Individual
Current assignee: Individual
Priority date: 2022-03-04
Filing date: 2022-03-04
Publication date: 2022-05-27

Abstract

The invention provides a composition for treating premature ejaculation by SS-PE and a preparation method thereof, belongs to the technical field of medicines, and relates to the composition for treating premature ejaculation by SS-PE, which comprises the following components: 0.5-1 part of methylene blue, 1-3 parts of benzyl alcohol, 0.8-1.5 parts of hyaluronic acid gel, 5-10 parts of lidocaine, 122-10 parts of vitamin B, 3-6 parts of ropivacaine and 90-100 parts of normal saline. The invention prepares methylene blue and ropivacaine vitamin B12 sodium hyaluronate in groups, and through a simple method of transdermal administration, the premature ejaculation can be effectively treated, and the tolerance of a patient to the treatment is very good.

Description

Composition for treating premature ejaculation by SS-PE and preparation method thereof

Technical Field

The invention relates to the technical field of medicines, in particular to a composition for treating premature ejaculation by SS-PE and a preparation method thereof.

Background

Recent advances in neurobiology, clinics, epidemiology, and observational research by clinicians and the pharmaceutical industry have provided perspectives in neuroanatomy and neurobiology, the scale of premature ejaculation, epidemiology, psychosocial and interpersonal effects, pathophysiology, etc. for ejaculation. Premature ejaculation, as we understand, has progressed from the initial assumption that premature ejaculation is a sexual disorder to a new degree of cognition. We now consider that: ejaculation latency is a genetically determined biological variable, and some people have inherent rapid ejaculation. Associated with this recognition, we have experienced the same changes in classification, definition, assessment, diagnosis and treatment of premature ejaculation.

The definition of lifelong premature ejaculation in the first multivariate evidence-based medicine of the current generation appeared in 2008, which was established by a group of international experts and characterized as: ejaculation invariably or almost invariably occurs within 1 minute after or prior to vaginal insertion, with each or almost every intravaginal insertion failing to delay ejaculation and with undesirable interpersonal relationships including pain, annoyance, frustration, and/or avoidance of intimate sexual behavior. This definition is limited to assessing intra-vaginal sexual intercourse patterns in heterosexual men. The support of published evidence of evidence-based medicine is insufficient for the definition of acquired premature ejaculation.

The treatment of premature ejaculation is only limited to the behavioral psychological treatment, and the drug therapy is expanded to be included at present, however, the external drugs, the internal drugs and the physical therapy in the market have poor curative effect, long treatment time and unstable curative effect.

Therefore, there is a need to provide a composition for treating premature ejaculation with SS-PE and a preparation method thereof, which solve the above existing problems.

Disclosure of Invention

In view of the above, the invention provides a composition for treating premature ejaculation by SS-PE and a preparation method thereof, and the composition has good treatment effect, short treatment time and stable treatment effect.

In order to solve the technical problems, the invention provides a composition for treating premature ejaculation by SS-PE, which comprises the following components: 0.5-1 part of methylene blue, 1-3 parts of benzyl alcohol, 0.8-1.5 parts of hyaluronic acid gel, 5-10 parts of lidocaine, 122-10 parts of vitamin B, 3-6 parts of ropivacaine and 90-100 parts of normal saline.

Further comprises 0.6-1 part of methylene blue, 3 parts of benzyl alcohol, 1 part of hyaluronic acid gel, 90 parts of normal saline and 5 parts of lidocaine.

Further comprises 1 part of methylene blue, 1 part of benzyl alcohol, 90 parts of normal saline and 128 parts of vitamin B.

Further, the paint comprises 1 part of methylene blue, 90 parts of physiological saline and 9 parts of lidocaine.

Further, the feed comprises 5 parts of methylene blue, 3 parts of ropivacaine and 122 parts of vitamin B.

Further, 3 parts of methylene blue, 6 parts of lidocaine and 1 part of sodium hyaluronate are included.

Further, the composition comprises methylene blue and ropivacaine, wherein the weight ratio of the methylene blue to the ropivacaine is 1: 2.

A method for preparing a composition for treating premature ejaculation by SS-PE comprises the following steps:

step 1, weighing the formulated amounts of methylene blue, ropivacaine, sodium hyaluronate, vitamin B12, absolute ethyl alcohol, propylene glycol, menthol, eucalyptus oil, castor oil, polysorbate 80 and p-hydroxybenzoate, mixing in a container, heating and stirring at 40-60 ℃ until the mixture is dissolved into a homogeneous solution for later use;

step 2, adding glycerol, sodium polyacrylate and sodium carboxymethyl cellulose into another container, and stirring until the glycerol, the sodium polyacrylate and the sodium carboxymethyl cellulose are completely dissolved for later use;

step 3, adding the balance of glycerol, the balance of sodium polyacrylate, sodium metabisulfite, the balance of sodium carboxymethylcellulose, glycine dihydroxy aluminum and aluminum hydroxide into another container, and stirring until all components are dissolved for later use;

step 4, mixing: adding purified water and the liquid medicine obtained in the step (2) into a mixing tank, and mixing uniformly; adding polyacrylic acid, and stirring uniformly; adding the liquid medicine obtained in the step (1) and stirring uniformly; and adding the liquid medicine obtained in the step 3 and kaolin, and uniformly mixing to obtain the pasty or gelatinous medicine composition.

The technical scheme of the invention at least comprises the following beneficial effects:

the invention prepares methylene blue and ropivacaine vitamin B12 sodium hyaluronate in groups, and through a simple method of transdermal administration, the premature ejaculation can be effectively treated, and the tolerance of a patient to the treatment is very good.

Detailed Description

In order to make the objects, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions of the embodiments of the present invention are clearly and completely described. It is to be understood that the embodiments described are only a few embodiments of the present invention, and not all embodiments. All other embodiments, which can be derived by a person skilled in the art from the described embodiments of the invention, are within the scope of the invention.

A composition for treating premature ejaculation by SS-PE comprises the following components: 0.5-1 part of methylene blue, 1-3 parts of benzyl alcohol, 0.8-1.5 parts of hyaluronic acid gel, 5-10 parts of lidocaine, 122-10 parts of vitamin B, 3-6 parts of ropivacaine and 90-100 parts of normal saline, wherein one or more of the components can form the following composition.

The composition 1 comprises 0.6-1 part of methylene blue, 3 parts of benzyl alcohol, 1 part of hyaluronic acid gel, 90 parts of normal saline and 5 parts of lidocaine.

Composition 2 comprises 1 part of methylene blue, 1 part of benzyl alcohol, 90 parts of normal saline and 128 parts of vitamin B.

Composition 3 comprises 1 part of methylene blue, 90 parts of physiological saline and 9 parts of lidocaine.

Composition 4 comprises 5 parts of methylene blue, 3 parts of ropivacaine and 122 parts of vitamin B.

Composition 5 comprises 3 parts of methylene blue, 6 parts of lidocaine and 1 part of sodium hyaluronate.

Composition 6 comprises methylene blue and ropivacaine in a weight ratio of 1: 2.

Methylene blue, methyl blue, chemically known as 3, 7-bis (dimethylamino) phenothiazine-5-poly (p-phenylene) chloride, also known as Methylene blue, royal blue, is an aromatic heterocyclic compound. Used as chemical indicators, dyes, biological stains, and drugs. The aqueous solution of methylene blue is blue in an oxidizing environment, but is reduced to a colorless state when encountering a reducing agent such as zinc, ammonia water and the like. High concentrations of methylene blue directly oxidize hemoglobin to methemoglobin. At low concentrations, reduced methylene blue is reduced by reduced coenzyme I dehydrogenase (NADPH), which reduces the ferredoxin to hemoglobin. It is also suitable for treating lithangiuria, thromboangiitis obliterans, and neurodermatitis clinically.

Methylene blue is an oxidizing agent, and has two different effects on hemoglobin according to different concentrations in vivo. At low concentration, hydrogen ions in the 6-phosphate-glucose dehydrogenation process are transferred to methylene blue through reduced pyridine triphosphate nucleoside to be converted into reduced white methylene blue; white methylene blue in turn transfers hydrogen ions to ferric methemoglobin with ferric iron, which is reduced to ferrous normal hemoglobin, and white methylene blue is oxidized to methylene blue. The reduction-oxidation process of methylene blue can be repeated. At high concentrations, methylene blue is not completely reduced to white methylene blue and therefore acts as an oxidizing agent, oxidizing normal hemoglobin to methemoglobin. Methemoglobin is easily combined with CN-to form cyanmethemoglobin, but after a few minutes both dissociate, so the toxicity of CN-to tissue poisoning can only be temporarily inhibited.

Methylene blue acts rapidly after intravenous injection, is excreted with urine without being metabolized basically, and can be absorbed under the pH condition of gastrointestinal tract after oral administration. And rapidly reduced to white methylene blue within the tissue. Within 6 days 74% was excreted in urine, 22% of which was in the original form, the remainder being white methylene blue, and some of which may be methylated. A small amount of methylene blue passes through the bile and is excreted by the feces. It is not easy to be absorbed from gastrointestinal tract by oral administration. Can be rapidly reduced to reduced white methylene blue in tissues and is partially metabolized. Methylene blue, reduced methylene blue and metabolites are all slowly excreted from urine; the unabsorbed portion of the intestinal tract is excreted in the feces, and the urine and feces may be colored blue.

Methylene blue is effective against methemoglobinemia caused by chemical substances of nitrite, nitrate, aniline, nitrobenzene, trinitrotoluene, benzoquinone, phenylhydrazine, etc. and drugs containing or generating aromatic amines (acetanilide, acetaminophen, phenacetin, benzocaine, etc.). Has poor effect on the methemoglobinemia caused by the deficiency of congenital reduction type pyridine diphosphate nucleoside methemoglobin reductase. Is ineffective for abnormal hemoglobin M with methemoglobinemia. Can temporarily delay the toxicity of acute cyanide poisoning.

Ropivacaine, chemical name (-) - (S) -N- (2, 6-dimethylphenyl) -1-N-propylpiperidine-2-carboxamide (S) -N- (2, 6-dimethylphenyl) -1-propyl-2-piperidinecarboxamide, melting point 144-146 ℃. [ α ] D23-82.0 ° (C ═ 2, methanol). pKa 8.16. Partition coefficient (1-octanol/aqueous buffer solution of Ph 7.4): 115.0. the traditional Chinese medicine composition is mainly used for blocking surgical operation areas, performing epidural anesthesia and relieving pain after epidural operation or childbirth in clinic.

Ropivacaine is the first pure levorotatory long-acting amide local anesthetic, and like other local anesthetics, reversible block is generated on impulse conduction along nerve fibers by blocking sodium ions flowing into nerve fiber cell membranes, so that the ropivacaine has the dual effects of anesthesia and analgesia, surgical anesthesia can be generated at a large dose, and non-progressive motor nerve block with only limitation is generated in sensory block (analgesia) at a small dose. Addition of epinephrine did not alter the strength and duration of block of ropivacaine.

Ropivacaine has a pKa of 8.1 and a distribution ratio of 141(25 ℃ C. n-octanol/phosphate buffer pH 7.4). The plasma concentration of the product depends on the dose, route of administration and the vascularity of the injection site. The composition is in accordance with linear pharmacokinetics, the absorption of the composition by epidural is complete in proportion to the maximum plasma concentration and the dosage, the composition is in two phases, the fast phase half-life period is 14 minutes, and the slow phase terminal half-life period is about 4 hours. Because slow absorption is the rate-limiting factor in the clearance of ropivacaine, epidural drugs have a longer clearance half-life than intravenous drugs. The total plasma clearance rate of ropivacaine is 440 ml/min. The clearance rate of free plasma is 8L/min. Renal clearance was 1ml/min, steady state volume of distribution was 47L, and terminal half-life was 1.8 hours. The liver-mediated metabolism rate of ropivacaine was 0.4. Mainly binds to alpha 1-acid glycoprotein in plasma, and the non-protein binding rate is about 6 percent. When continuous epidural injection, an increase in the total plasma concentration of ropivacaine was observed, which was associated with an increase in the post-operative alpha 1-acid glycoprotein concentration, with the change in unbound (pharmacologically active) concentration being much smaller than the change in total plasma concentration. Ropivacaine readily permeates the placenta and equilibrates rapidly with respect to unbound concentrations. In the fetus, ropivacaine binds to plasma proteins to a lower extent than in the mother, and the total plasma concentration in the fetus is also lower than in the mother. Ropivacaine is extensively metabolized primarily by aromatic hydroxylation, with 86% of the total dose being excreted after intravenous injection via the urine, of which only 1% is associated with unmetabolized drugs. The major metabolite is 3-hydroxy ropivacaine, about 37% of which is excreted as a conjugate from the urine, and about 1% to 3% of the excreted 4-hydroxy ropivacaine, N-dealkylmetabolite and 4-hydroxydealkylmetabolite from the urine. Bound and unbound 3-hydroxypivacaine showed only detectable concentrations in plasma. 3-hydroxy ropivacaine and 4-hydroxy ropivacaine have local anesthetic action, but the anesthetic action is weaker than ropivacaine.

Vitamin B12, also called cobalamin, is a polycyclic compound containing 3-valent cobalt, and 4 reduced pyrrole rings are linked together to become 1 corrin macrocycle (similar to porphyrin), which is the only vitamin containing metal elements. The vitamin B12 is red crystal powder, has no smell and taste, is slightly soluble in water and ethanol, is most stable under the condition of pH 4.5-5.0 and weak acid, and can be decomposed in strong acid (pH < 2) or alkaline solution to a certain extent when being heated. Higher animals and plants cannot produce vitamin B12, and vitamin B12 in nature is synthesized by microorganisms. Vitamin B12 is the only vitamin that needs the help of intestinal secretions (endogenous factors) to be absorbed, and is involved in the production of bone marrow red blood cells, prevention of pernicious anemia, and prevention of damage to the cerebral nerves.

Sodium hyaluronate, with the chemical formula of (C14H20NO11Na) n, is an inherent component in human body, is dextran aldehyde acid, has NO species specificity, and is widely present in tissues such as placenta, amniotic fluid, crystalline lens, articular cartilage, skin dermis and the like; it is distributed in cytoplasm and intercellular substance, and has lubricating and nourishing effects on cells and cell organs contained therein.

It is a kind of gel prepared by compounding natural hyaluronic acid with other cell regenerating and wrinkle eliminating medicine and is used through injection.

The moisturizing effect is the most important effect of sodium hyaluronate in cosmetics, and the relative humidity of the surrounding environment has less influence on the moisturizing effect compared with other moisturizing agents.

The benzyl alcohol injection is used as antiseptic. Can be used for topical pain relief and preservation of the preparation.

Lidocaine (Lidocaine), a local anesthetic and antiarrhythmic drug, is a derivative of cocaine, but has no components of cocaine that produce hallucinations and addiction. The hydrochloride of the lidocaine is white crystalline powder, is dissolved in water to a minimum degree, has toxicity equivalent to procaine, has stronger and durable local anesthesia effect and good surface penetrating power, and can be injected and used for surface anesthesia. Lidocaine is a very good local anaesthetic, generally acting after one to three minutes of administration, with the effect remaining for one to three hours. Can be used for treating oral ulcer. It has not been used very often as a cardiac rhythm disorder drug because of concerns about its long-term side effects. Few people are allergic to lidocaine. The traditional Chinese medicine composition is used for treating arrhythmia in 1963, is a medicine for preventing and treating acute myocardial infarction and various heart diseases complicated with rapid ventricular arrhythmia, and is a first-choice medicine for ventricular premature beat, ventricular tachycardia and ventricular tremor of acute myocardial infarction.

Example 1

The compositions of the present invention are prepared.

Formulation (per 100 g): 4.05g of methylene blue, 4.10g of ropivacaine, 6.25g of absolute ethanol, 0.25g of propylene glycol, 0.85g of menthol, 0.50g of eucalyptus oil, 0.25g of polysorbate 80, 0.15g of methylparaben, 7.50g of glycerol, 3.05g of sodium polyacrylate, 3.05g of sodium carboxymethylcellulose, 0.09g of dihydroxyaluminum glycine, 0.10g of aluminum hydroxide, 3.45g of polyacrylic acid, 1.11g of kaolin, and water added to the total amount.

A preparation method of a composition for treating premature ejaculation by SS-PE, namely SS-PE cataplasm, gel, paste and other external medicines, comprises the following steps:

step 1, weighing the formulated amounts of methylene blue, ropivacaine, sodium hyaluronate, vitamin B12, absolute ethyl alcohol, propylene glycol, menthol, eucalyptus oil, castor oil, polysorbate 80 and p-hydroxybenzoate, mixing in a container, heating and stirring at 60 ℃ for about 3 hours until the mixture is dissolved into a homogeneous solution for later use;

step 2, adding glycerol, sodium polyacrylate and sodium carboxymethyl cellulose in the amount which is half of the prescription into another container, and stirring until the glycerol, the sodium polyacrylate and the sodium carboxymethyl cellulose are completely dissolved for later use;

step 4, mixing: adding purified water and the liquid medicine obtained in the step (2) into a mixing tank, and mixing uniformly; adding polyacrylic acid, and stirring uniformly; adding the liquid medicine obtained in the step 1, and uniformly stirring; and adding the liquid medicine obtained in the step 3 and kaolin, and uniformly mixing to obtain the pasty or gelatinous medicine composition.

The transdermal patch prepared by applying the gel-like pharmaceutical composition to a nonwoven fabric and coating the nonwoven fabric with a plastic film can be prepared by cutting the plaster into 100X 100mm pieces, or preparing the plaster or gel, wherein the plaster content is usually controlled to be in the range of 5 to 20g/100 cm, in this example 7.5g/100 cm, and the plaster is usually called plaster or gel plaster.

Example 2

SS-PE injection, formulation (in per 100 g): 1g of methylene blue, 3 g of benzyl alcohol, 1g of hyaluronic acid gel, 90g of physiological saline and 5g of lidocaine.

Example 3

SS-PE injection, formulation (in per 100 g): 1g of methylene blue, 1g of benzyl alcohol, 90g of normal saline and vitamin B128 g.

Example 4

SS-PE injection, formula (in per 100 g): 1g of methylene blue, 90g of physiological saline and 9g of lidocaine.

The SS-PE injection is used for treating operation in the steps of inserting a 27-gauge injection needle from the front end of the glans penis to about 1/3 positions of a coronary sulcus to the subcutaneous part under local anesthesia, and firstly injecting 2 ml of SS-PE to increase the fluctuation of the glans penis. 2 ml of SS-PE is injected into the root of the penis by a one-ml injection needle with 0.2 of each side of the injection frenulum and 0.2 ml of each point of the abdomen side of the penis downwards divided into eight points along the frenulum.

Typical cases are listed below

Typical case 1

Wangzhi, male, age 36, first diagnosis: 2017, 1, 15.

The main complaints are: ejaculation was too fast, for more than half a year.

The current medical history: the patient marries for 8 years, the sexual life is normal when the patient complains of the early marriage, the penis is good in erection and healthy, no special disease history exists, and a woman is born and is healthy. In recent years, the ejaculation time is kept about 1 minute in average each ejaculation time due to busy work, fatigue, irregular life and premature ejaculation, which affects the harmony of sexual life of couples, and the couple emotion is influenced to a certain extent. There was a history of masturbation, and the history of prostatitis and urethritis was denied.

Special examination: the penis is developed normally, the prepuce is not long, the external orifice of the urethra is not red and swollen, and abnormal secretion is not generated.

Auxiliary inspection: urine analysis was normal. Prostate fluid is normal routinely. Penile erectile nerves: (+++), penile ultrasound hemogram: the penis artery can supply blood.

And (3) Western diagnosis: premature ejaculation.

Traditional Chinese medicine diagnosis: premature ejaculation (fire excess from yin deficiency).

Typical case 2

Poplar, male, 26 years old, first visit: year 2018, 3 month 9 day.

The main complaints are: ejaculation was too fast and was over two months.

The current medical history: the patient is newly married for less than three months, and ejaculation is carried out after less than two minutes of sexual intercourse, so that the couple is not emotional. Usually, insomnia and dreamful sleep, poor erection, low libido, soreness of the waist, and thin and white tongue coating. There was a history of masturbation, and the history of prostatitis and urethritis was denied.

And (3) Western diagnosis: premature ejaculation.

Typical case 3

Pangzao, male, age 44, first diagnosis: 12 and 10 months in 2017.

The main complaints are: ejaculation was too fast, more than 3 years.

The current medical history: the patient was married for 17 years, and had a sexual life after the marrying. The sexual intercourse can be done naturally, but the ejaculation can be done just when the penis contacts the vaginal opening of the wife, and the penis can not enter the vagina for sexual intercourse. Restlessness, dream-disturbed sleep, soreness and weakness of the waist and legs, red tongue with little coating. There was a history of masturbation, and the history of prostatitis and urethritis was denied.

Special examination: the penis is normally developed, the prepuce is not long, the external orifice of the urethra is not red and swollen, and abnormal secretion is not generated.

And (3) Western diagnosis: premature ejaculation

The present invention will be further described below by the statistics of the treatment effect of premature ejaculation of patients in each example. The counted number of patients totals 100, and the following conditions are met:

(1) the patient has ejaculation occurring before or within 3 minutes of inserting the penis into the vagina during at least 75% of intercourse;

(2) male;

(3) age 18-62 years;

(4) the patient can keep stable sexual relation with the opposite sex for at least 3 months during the treatment period;

(5) premature ejaculation occurred for at least two months before treatment;

(6) healthy persons without a history of disease or any physical examination abnormalities, laboratory examination abnormalities, imaging examination abnormalities, and electrocardiographic examination abnormalities;

(7) patients are willing to discontinue other types of conventional therapy, including medications, behavioral therapy, or topical therapy.

The treatment groups 1 to 4 were treated with the compositions of examples 1 to 4, respectively, and the control group was treated with the commercially available conventional premature ejaculation-treating drugs, and the statistical criteria of the treatment effects after 2 months of treatment are shown in table 1:

TABLE 1

As can be seen from Table 1, the present invention has an obvious effect on treating premature ejaculation.

In addition, after treatment, the average net increase of the maximum glans circumference of the patient is 16.58 (12-17) mm; the patient satisfaction rate is 96.8%; the spouse satisfaction rate is 90%. The principle is that the filling agent is used for increasing the volume of the glans penis and the long-acting anesthesia action is used for blocking stimulation from reaching the glans receptor, and the sensitivity of the glans penis is reduced, so that the aim of treating premature ejaculation is fulfilled.

The foregoing is a preferred embodiment of the present invention, and it should be noted that it would be apparent to those skilled in the art that various modifications and enhancements can be made without departing from the principles of the invention, and such modifications and enhancements are also considered to be within the scope of the invention.

Claims

1. A composition of SS-PE for treating premature ejaculation, comprising the following components: 0.5-1 part of methylene blue, 1-3 parts of benzyl alcohol, 0.8-1.5 parts of hyaluronic acid gel, 5-10 parts of lidocaine, 122-10 parts of vitamin B, 3-6 parts of ropivacaine and 90-100 parts of normal saline.

2. The composition for treating premature ejaculation as claimed in claim 1, comprising 0.6-1 part of methylene blue, 3 parts of benzyl alcohol, 1 part of hyaluronic acid gel, 90 parts of physiological saline and 5 parts of lidocaine.

3. The composition of claim 1, comprising 1 part of methylene blue, 1 part of benzyl alcohol, 90 parts of normal saline and 128 parts of vitamin B.

4. The composition of claim 1, comprising 1 part of methylene blue, 90 parts of saline and 9 parts of lidocaine for treating premature ejaculation by SS-PE.

5. The SS-PE composition for treating premature ejaculation as claimed in claim 1, comprising 5 parts of methylene blue, 3 parts of ropivacaine and 122 parts of vitamin B.

6. The composition of claim 1, comprising 3 parts of methylene blue, 6 parts of lidocaine and 1 part of sodium hyaluronate.

7. The SS-PE composition for treating premature ejaculation as claimed in claim 1, comprising methylene blue and ropivacaine in a weight ratio of 1: 2.

8. A process for the preparation of a composition for the treatment of premature ejaculation by SS-PE according to any of claims 1 to 7, comprising the following steps: