CN114642629A - Compound gel preparation and preparation method, administration mode and application thereof - Google Patents
Compound gel preparation and preparation method, administration mode and application thereof Download PDFInfo
- Publication number
- CN114642629A CN114642629A CN202210283923.7A CN202210283923A CN114642629A CN 114642629 A CN114642629 A CN 114642629A CN 202210283923 A CN202210283923 A CN 202210283923A CN 114642629 A CN114642629 A CN 114642629A
- Authority
- CN
- China
- Prior art keywords
- umbilical cord
- compound gel
- gel preparation
- cord mesenchymal
- mesenchymal stem
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/475—Quinolines; Isoquinolines having an indole ring, e.g. yohimbine, reserpine, strychnine, vinblastine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
- A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
- A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/28—Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/20—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0034—Urogenital system, e.g. vagina, uterus, cervix, penis, scrotum, urethra, bladder; Personal lubricants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/08—Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/10—Drugs for genital or sexual disorders; Contraceptives for impotence
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Reproductive Health (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Gynecology & Obstetrics (AREA)
- Developmental Biology & Embryology (AREA)
- Organic Chemistry (AREA)
- Cell Biology (AREA)
- Immunology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Endocrinology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Molecular Biology (AREA)
- Zoology (AREA)
- Virology (AREA)
- Biotechnology (AREA)
- Biomedical Technology (AREA)
- Hematology (AREA)
- Pregnancy & Childbirth (AREA)
- Urology & Nephrology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention discloses a compound gel preparation, a preparation method, a drug delivery mode and application thereof. The preparation method comprises the following steps: s1 selecting human umbilical cord mesenchymal stem cells, providing ginsenoside Rb, yohimbine hydrochloride, medicinal high molecular stabilizer, humectant and dimethyl sulfoxide. S2, carrying out starvation culture-enrichment concentration on the human umbilical cord mesenchymal stem cells to obtain umbilical cord mesenchymal stem cell exosome concentrated solution. S3 sequentially adding ginsenoside Rb, yohimbine hydrochloride, medicinal polymer stabilizer, humectant and dimethyl sulfoxide into the umbilical cord mesenchymal stem cell exosome concentrated solution, and mixing to obtain the compound gel preparation. According to the invention, the human umbilical cord mesenchymal exosome extract can be obtained in a short time, meanwhile, the recovery efficiency is obviously improved, the recovery mode is simpler and more convenient, and the compound gel preparation with an obvious curative effect on erectile dysfunction can be prepared.
Description
Technical Field
The invention relates to a gel preparation, in particular to a compound gel preparation, and also relates to a preparation method, a drug delivery mode and application of the compound gel preparation.
Background
Erectile Dysfunction (ED) is the most common disorder of male sexual dysfunction, which is mainly manifested by the inability to achieve and sustain an erection for satisfactory intercourse, with the course lasting for more than 3 months. ED is generally classified into organic, operative, traumatic, psychogenic and penile lesion, and the conventional treatment method is oral drug treatment, but the treatment method has strong dependence on drugs and cannot achieve the purpose of radical treatment.
Disclosure of Invention
Based on this, it is necessary to provide a compound gel preparation, a preparation method, a drug delivery mode and an application thereof aiming at the problems that the current oral drug treatment of erectile dysfunction is mainly carried out, the dependence on the drug is strong, and the purpose of radical treatment cannot be achieved.
A preparation method of a compound gel preparation comprises the following steps:
s1 selecting human umbilical cord mesenchymal stem cells, providing ginsenoside Rb, yohimbine hydrochloride, medicinal polymer stabilizer, humectant and dimethyl sulfoxide;
s2 starvation culture-enrichment concentration is carried out on the human umbilical cord mesenchymal stem cells to obtain umbilical cord mesenchymal stem cell exosome concentrated solution;
the starvation culture method comprises the following specific operations:
s21 inoculating the human umbilical cord mesenchymal stem cells into a culture medium;
s22 inoculating and culturing for 2-4 days, sucking and removing all culture supernatant, washing for 2-4 times by using medical compound electrolyte injection, adding compound electrolyte solution, and placing in a carbon dioxide incubator for starvation culture;
s23, after starvation culture for 18-30 h, recovering all culture supernatants, filtering with a filter membrane, and recovering centrifugal supernatants after centrifugation;
s24, continuously centrifuging the centrifugal supernatant, sucking and discarding 70-90% of liquid in the supernatant, and mixing the precipitate with the residual supernatant to obtain an umbilical cord mesenchymal stem cell exosome concentrated solution;
s3 sequentially adding ginsenoside Rb, yohimbine hydrochloride, medicinal polymer stabilizer, humectant and dimethyl sulfoxide into the umbilical cord mesenchymal stem cell exosome concentrated solution, and mixing to obtain the compound gel preparation.
According to the preparation method, the umbilical cord mesenchymal stem cells are subjected to starvation culture to promote the secretion of bioactive substances of the umbilical cord mesenchymal stem cells, the bioactive substances secreted by the umbilical cord mesenchymal stem cells are recovered in an exosome form, the human umbilical cord mesenchymal exosome extract can be obtained in a short time, the recovery efficiency is obviously improved, the recovery mode is simpler and more convenient, and in addition, the exosome is concentrated through ultracentrifugation to improve the concentration of the exosome.
In one embodiment, the selection criteria of the human umbilical cord mesenchymal stem cells are: selecting stem cells with good growth state and negative microbial detection from the human umbilical cord mesenchymal stem cells of the generations P2-P8.
In one embodiment, the medicinal polymer stabilizer is any one of sodium alginate, sodium hyaluronate, chitosan and hydroxyethyl starch; the humectant is propylene glycol and glycerin.
In one embodiment, the inoculation density is 3-5 x 104/cm2(ii) a The culture medium contains fetal calf serum with volume ratio concentration of 5-15%.
In one embodiment, each 1000ml of the compound electrolyte solution comprises 5.26g of sodium chloride, 5.02g of sodium gluconate, 3.68g of sodium acetate, 0.37g of potassium chloride and 0.30g of magnesium chloride.
In one embodiment, the pore size of the filter is 0.22 um; and centrifuging the supernatant filtered by the filter membrane for 10-20 min under the centrifugal force condition of 3000-5000 g.
In one embodiment, the umbilical cord mesenchymal stem cell exosome concentrate is biologically active.
The compound gel preparation is prepared by the preparation method of the compound gel preparation, and each 100ml of the compound gel preparation comprises the following components: 50ml of umbilical cord mesenchymal stem cell exosome concentrated solution, 5ml of ginsenoside Rb15g, 5ml of yohimbine hydrochloride, 10g of medicinal high-molecular stabilizer, 10ml of humectant and 10ml of dimethyl sulfoxide.
The compound gel preparation contains umbilical cord mesenchymal stem cell exosome concentrated solution obtained by starvation culture of 5-9 times concentrated umbilical cord mesenchymal stem cells, can promote angiogenesis, regulate local tissue microenvironment and improve local blood supply, so that the effects of improving penis blood supply and treating erectile dysfunction are achieved, in addition, a compound preparation is prepared by matching yohimbine hydrochloride and ginsenoside Rb1, the curative effect is increased, the stability and activity of exosomes can be furthest increased by cooperatively adding a humectant and an absorption enhancer (dimethyl sulfoxide), the transdermal absorption capacity of exosomes is improved, and the treatment effect is greatly improved.
The administration mode of the compound gel preparation comprises the following specific operations: the compound gel preparation is directly smeared on the skin of penis and glans and directly absorbed by the skin for administration; wherein the compound gel preparation is prepared by adopting the preparation method of the compound gel preparation.
Application of a compound gel preparation in treating male erectile dysfunction is provided.
Compared with the prior art, the invention has the beneficial effects that:
according to the preparation method, the umbilical cord mesenchymal stem cells are subjected to starvation culture to promote secretion of bioactive substances of the umbilical cord mesenchymal stem cells, the bioactive substances secreted by the umbilical cord mesenchymal stem cells are recovered in an exosome form, the human umbilical cord mesenchymal exosome extract can be obtained in a short time, meanwhile, the recovery efficiency is obviously improved, the recovery mode is simpler and more convenient, and in addition, the exosome is concentrated through ultracentrifugation to improve the concentration of the exosome.
The compound gel preparation disclosed by the invention contains umbilical cord mesenchymal stem cell exosome concentrated solution obtained by starvation culture of 5-9 times concentrated umbilical cord mesenchymal stem cells, can promote angiogenesis, regulate local tissue microenvironment and improve local blood supply, so that the effects of improving penis blood supply and treating erectile dysfunction are achieved, in addition, a compound preparation is prepared by matching yohimbine hydrochloride and ginsenoside Rb1, the curative effect is increased, the stability and activity of exosomes can be furthest increased by cooperatively adding a humectant and an absorption enhancer (dimethyl sulfoxide), the transdermal absorption capacity of exosomes is improved, and the treatment effect is greatly improved.
Drawings
FIG. 1 is a graph showing a comparison of sexual life before and after treatment in Experimental example 1 of the present invention.
FIG. 2 is a graph showing a comparison of sexual life before and after treatment in Experimental example 2 of the present invention.
FIG. 3 is a graph showing a comparison of sexual life before and after treatment in Experimental example 3 of the present invention.
Detailed Description
The present invention will be described in detail below with reference to the accompanying drawings.
Example 1
The embodiment provides a preparation method of a compound gel preparation, which comprises the following steps:
s1 selecting human umbilical cord mesenchymal stem cells, providing ginsenoside Rb, yohimbine hydrochloride, medicinal polymer stabilizer (sodium hyaluronate), humectant (propylene glycol and glycerol) and dimethyl sulfoxide (transdermal absorption enhancer).
The selection standard of the human umbilical cord mesenchymal stem cells is as follows: and selecting stem cells with good growth state and negative microbial detection from the human umbilical cord mesenchymal stem cells of the generations P2-P8. Yohimbine hydrochloride is an extract from dried bark of the african plant yohimbine, which is produced by medusde biotechnology limited. Ginsenoside Rb1 is produced by WUKEQI Biotech limited, Sichuan province.
S2 starvation culture-enrichment concentration is carried out on the human umbilical cord mesenchymal stem cells, and umbilical cord mesenchymal stem cell exosome concentrated solution is obtained.
The umbilical cord mesenchymal stem cell exosome concentrated solution has biological activity.
The starvation culture method comprises the following specific operations:
s21 inoculating the human umbilical cord mesenchymal stem cells into a culture medium.
The inoculation density is 3-5 x 104/cm2. The culture medium can be placed in a cell culture bottle or cell cultureIn the dish, the culture medium contains fetal calf serum with volume ratio concentration of 5-15%.
And S22 inoculating and culturing for 2-4 days, sucking and removing all culture supernatant, washing for 2-4 times by using the medical compound electrolyte injection, adding the compound electrolyte solution, and placing in a carbon dioxide incubator for starvation culture.
The compound electrolyte solution is produced by Sichuan Konlun pharmaceutical industry Co., Ltd, and each 1000ml of the compound electrolyte solution contains 5.26g of sodium chloride, 5.02g of sodium gluconate, 3.68g of sodium acetate, 0.37g of potassium chloride and 0.30g of magnesium chloride. After inoculation culture is carried out for 2-4 days, the cell fusion rate reaches 80% -95%, the cell growth state is good, all culture supernatant is sucked and discarded, the cells are cleaned for 2-4 times by using the compound electrolyte injection, then the compound electrolyte solution is added, the height of the solution reaches 2-3 mm, and the solution is placed into a carbon dioxide incubator for starvation culture.
S23 starvation culture is carried out for 18-30 h, all culture supernatant is recovered and filtered by a filter membrane, and centrifugal supernatant is recovered after centrifugation.
The aperture of the filter membrane is 0.22um, and the supernatant filtered by the filter membrane is centrifuged for 10-20 min under the centrifugal force condition of 3000-5000 g.
S24, continuously centrifuging the centrifugal supernatant, sucking and discarding 70-90% volume of liquid in the supernatant, and mixing the precipitate and the residual supernatant to obtain the umbilical cord mesenchymal stem cell exosome concentrated solution.
And (3) putting the recovered centrifugal supernatant into a centrifugal tube, centrifuging for 30-60 min under the centrifugal force condition of 200000-500000 g, gently taking out the centrifugal tube after centrifugation is finished, sucking 70-90% of liquid by using a pipette, uniformly mixing the remaining 10-30% of liquid by volume with precipitate at the bottom of the centrifugal tube, and taking the mixture as a raw material for preparing the erectile dysfunction treatment preparation, namely the umbilical cord mesenchymal stem cell exosome concentrated solution.
S3 sequentially adding ginsenoside Rb, yohimbine hydrochloride, medicinal high-molecular stabilizer (sodium hyaluronate), humectant (propylene glycol and glycerol) and dimethyl sulfoxide into the umbilical cord mesenchymal stem cell exosome concentrated solution, and mixing to obtain the compound gel preparation.
According to the preparation method, the umbilical cord mesenchymal stem cell exosome with high concentration and bioactivity is obtained by starvation culture of umbilical cord mesenchymal stem cells and enrichment and concentration, the hunger culture of the umbilical cord mesenchymal stem cells is performed to promote the secretion of bioactive substances of the umbilical cord mesenchymal stem cells, the bioactive substances secreted by the umbilical cord mesenchymal stem cells are recovered in an exosome form, the human umbilical cord mesenchymal exosome extract can be obtained in a short time, meanwhile, the recovery efficiency is obviously improved, the recovery mode is simpler and more convenient, in addition, the exosome is concentrated through ultracentrifugation, and the concentration of the exosome is improved. According to the preparation method, yohimbine hydrochloride and ginsenoside Rb1 are added to prepare the external concentrated compound gel preparation for treating erectile dysfunction by external application of the umbilical cord mesenchymal stem cell exosome, and the curative effect is remarkable.
In the preparation method of the present example,
example 2
This example provides a compound gel formulation prepared using the method of preparation of a compound gel formulation as in example 1. The compound gel preparation per 100ml comprises the following components: 50ml of umbilical cord mesenchymal stem cell exosome concentrated solution, ginsenoside Rb15g, 5ml of yohimbine hydrochloride, 10g of medicinal high-molecular stabilizer (sodium hyaluronate), 10ml of humectant (propylene glycol and glycerol) and 10ml of dimethyl sulfoxide.
In the embodiment, the exosome component of the umbilical cord mesenchymal stem cell exosome concentrated solution has bioactivity, and the release of cytokines (such as VEGF and fibroblast growth factor) in the exosome can promote angiogenesis, regulate the local tissue microenvironment and improve local blood supply, so that the effects of improving the blood supply of the penis and treating erectile dysfunction are achieved. The yohimbine hydrochloride is added to increase blood flow of cavernous sinus of penis by dilating human stem artery, so as to make penis engorge and erect, and also produce psychological excitation effect to increase libido, and in addition, can make smooth muscle of cavernous body of penis reach maximum relaxation effect. In the embodiment, the ginsenoside Rb1 is added to accelerate the sexual maturation process, so that the sexual function and the sexual organ development are well promoted, the sexual behavior reduction caused by the stimulation is also well improved, and the ginsenoside Rb1 plays a role in improving the sexual function by increasing the androgen level and activating the NO/cGMP pathway.
Ginsenoside Rb1 can accelerate sexual maturation process, promote sexual function and sexual organ development, improve sexual behavior disorder caused by stress, and improve sexual function by increasing androgen level and activating NO/cGMP pathway. The invention adopts a method of hungry umbilical cord mesenchymal stem cells, can obtain the human umbilical cord mesenchymal exosome extract in a short time, and is concentrated by an ultracentrifugation method to obtain high-concentration human umbilical cord mesenchymal stem cell exosomes.
The embodiment also provides a drug delivery mode of the compound gel preparation, and the compound gel preparation is directly smeared on the skin of the penis and the glans and directly absorbed through the skin for drug delivery.
The compound gel preparation of the embodiment contains umbilical cord mesenchymal stem cell exosome concentrated solution obtained by starvation culture of umbilical cord mesenchymal stem cells concentrated by 5-9 times, can promote angiogenesis, regulate local tissue microenvironment and improve local blood supply, so that the effects of improving penis blood supply and treating erectile dysfunction are achieved, in addition, a compound preparation is prepared by matching yohimbine hydrochloride and ginsenoside Rb1, the curative effect is increased, the stability and activity of exosomes can be furthest increased by cooperatively adding a humectant and an absorption enhancer (dimethyl sulfoxide), the transdermal absorption capacity of exosomes is improved, and the treatment effect is greatly improved.
Next, the treatment experiment of symptoms of erectile dysfunction using the compound gel preparation of the present invention was conducted, and the experimental process and the experimental results were as follows.
Experimental example 1
The patient Wangzhi (32 years old) has hyposexuality, decreased sexual frequency and early symptoms of erectile dysfunction before one year due to high pressure of work life, and the sexual frequency is averagely 1 time per week within 4 months before treatment, wherein the sexual life is not completed due to abnormal erection of penis for 2 times. During sexual intercourse, the penis fails to maintain erection before ejaculation for 5 times, and ejaculation fails. The sexual intercourse process was completed for another 9 times, with an average time of less than 3 min. The self-evaluation score of the national erectile dysfunction index is 13 points, and the mild erectile dysfunction belongs to.
The patient is treated by the compound gel preparation (the treatment period is four weeks), the whole glans penis of the penis is smeared with the compound gel preparation every day after the penis is cleaned before going to sleep in the morning, at noon and at night, 1-2 ml of the compound gel preparation is smeared every time, and the compound gel preparation is guaranteed to be completely absorbed. During the treatment, the patients maintain the sexual life frequency of 1 time/week, and the erection conditions are not counted. After four weeks of treatment, the compound gel preparation is not used, the patients have 5 times of sexual life within one month, ejaculation is completed successfully, and the average sexual intercourse time reaches 6 min. Referring to fig. 1, fig. 1 is a comparison graph of sexual life time before and after treatment of wangzhi, and the comparison shows that the treatment effect is obvious and the difference is significant (p is less than 0.01), which proves that the compound gel preparation of the invention has significant efficacy in the treatment of erectile dysfunction.
Experimental example 2
The patient is plum (36 years old) and suffers from diabetes for more than 2 years, the sexual life frequency is reduced, and obvious symptoms of erectile dysfunction appear. Before treatment, the sexual life frequency is 1 time/week in 3 months on average. And (5) counting the sexual life quality of 3 months, wherein the sexual life is not finished for 3 times because the penis cannot erect normally. During sexual intercourse, the penis fails to maintain erection before ejaculation for 5 times, and ejaculation fails. The intercourse process was completed for another 4 times, with an average time of less than 3 min. The self-test score of 9 points according to the International erectile function index belongs to moderate erectile dysfunction.
The patient is treated by the compound gel preparation (the treatment period is four weeks), the whole glans penis is smeared with the compound gel preparation every day after the penis is cleaned before going to sleep in the morning, noon and evening, and 1-2 ml of the compound gel preparation is smeared every time, so that the compound gel preparation is ensured to be completely absorbed. During the treatment process, the patients have had sexual lives twice, and the erection condition is not counted during the period. After four weeks of treatment, the compound gel preparation is not used, the patients have sexual life for 9 times within 3 months, ejaculation is completed successfully, and the average sexual intercourse time reaches 5.4 min. Referring to fig. 2, fig. 2 is a graph showing the comparison of sexual life time before and after a certain treatment of plum, and the comparison shows that the treatment effect is obvious and the difference is significant (p < 0.01). This demonstrates that the compound gel formulation of the present invention has significant efficacy in the treatment of erectile dysfunction.
Experimental example 3
The patient is juezhi (38 years old), the manager is sold, and the work pressure is high. In the last 1 year, the sexual life frequency is reduced, the average sexual life frequency is 1 time per week in 7 months before treatment, and obvious symptoms of erectile dysfunction appear. And (5) counting the sexual life quality of nearly 3 months, wherein the sexual life is not finished because the penis cannot erect normally for 2 times. During sexual intercourse, the penis fails to maintain erection before ejaculation for 4 times, and ejaculation fails. The sexual intercourse process is completed for another 6 times, and the average time is less than 4 min. The self-evaluation score of the national erectile dysfunction index is 13 points, and the mild erectile dysfunction belongs to.
The patient is treated by the compound gel preparation (the treatment period is four weeks), the whole glans penis is smeared with the compound gel preparation every day after the penis is cleaned before going to sleep in the morning, noon and evening, and 1-2 ml of the compound gel preparation is smeared every time, so that the compound gel preparation is ensured to be completely absorbed. During the treatment, the patients had 4 sexual lives, and the erection during the period was not counted. After four weeks of treatment, the compound gel preparation is not used, the patients have 15 sexual lives within 3 months, ejaculation is completed successfully, and the average sexual intercourse time reaches 7.5 min. Referring to fig. 3, fig. 3 is a comparison graph of the sexual life time before and after treatment of cinnabar, and the comparison shows that the treatment effect is obvious and the difference is significant (p is less than 0.01), which proves that the compound gel preparation of the present invention has significant efficacy in the treatment of erectile dysfunction.
Claims (10)
1. The preparation method of the compound gel preparation is characterized by comprising the following steps:
s1 selecting human umbilical cord mesenchymal stem cells, providing ginsenoside Rb, yohimbine hydrochloride, medicinal polymer stabilizer, humectant and dimethyl sulfoxide;
s2 starvation culture-enrichment concentration is carried out on the human umbilical cord mesenchymal stem cells to obtain umbilical cord mesenchymal stem cell exosome concentrated solution;
the starvation culture method comprises the following specific operations:
s21 inoculating the human umbilical cord mesenchymal stem cells into a culture medium;
s22 inoculating and culturing for 2-4 days, sucking and removing all culture supernatant, washing for 2-4 times by using medical compound electrolyte injection, adding compound electrolyte solution, and placing in a carbon dioxide incubator for starvation culture;
s23, after starvation culture for 18-30 h, recovering all culture supernatants, filtering with a filter membrane, and recovering centrifugal supernatants after centrifugation;
s24, continuously centrifuging the centrifugal supernatant, sucking and discarding 70-90% of liquid in the supernatant, and mixing the precipitate with the residual supernatant to obtain an umbilical cord mesenchymal stem cell exosome concentrated solution;
s3 sequentially adding ginsenoside Rb, yohimbine hydrochloride, medicinal polymer stabilizer, humectant and dimethyl sulfoxide into the umbilical cord mesenchymal stem cell exosome concentrated solution, and mixing to obtain the compound gel preparation.
2. The method for preparing a compound gel preparation according to claim 1, wherein the selection criteria of the human umbilical cord mesenchymal stem cells are: and selecting stem cells with good growth state and negative microbial detection from the human umbilical cord mesenchymal stem cells of the generations P2-P8.
3. The preparation method of the compound gel preparation according to claim 1, wherein the medicinal polymer stabilizer is any one of sodium alginate, sodium hyaluronate, chitosan and hydroxyethyl starch;
the humectant is propylene glycol and glycerin.
4. The method for preparing a compound gel formulation according to claim 1, wherein the seeding density is 3-5 x 104/cm2;
The culture medium contains fetal calf serum with volume ratio concentration of 5-15%.
5. The preparation method of the compound gel preparation as claimed in claim 1, wherein each 1000ml of the compound electrolyte solution comprises 5.26g of sodium chloride, 5.02g of sodium gluconate, 3.68g of sodium acetate, 0.37g of potassium chloride and 0.30g of magnesium chloride.
6. The method for preparing a compound gel preparation according to claim 1, wherein the pore size of the filter membrane is 0.22 um;
and centrifuging the supernatant filtered by the filter membrane for 10-20 min under the centrifugal force condition of 3000-5000 g.
7. The method for preparing a compound gel preparation according to claim 1, wherein the umbilical cord mesenchymal stem cell exosome concentrated solution has biological activity.
8. A compound gel preparation prepared by the preparation method of the compound gel preparation as claimed in any one of claims 1 to 7, wherein the components of the compound gel preparation per 100ml are as follows: 50ml of umbilical cord mesenchymal stem cell exosome concentrated solution, 5ml of ginsenoside Rb15g, 5ml of yohimbine hydrochloride, 10g of medicinal high-molecular stabilizer, 10ml of humectant and 10ml of dimethyl sulfoxide.
9. The administration mode of the compound gel preparation is characterized by comprising the following specific operations: the compound gel preparation is directly smeared on the skin of the penis and the glans and directly absorbed by the skin for administration; wherein the compound gel preparation is prepared by the preparation method of the compound gel preparation as claimed in any one of claims 1 to 7.
10. Application of a compound gel preparation in treating male erectile dysfunction is provided.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202210283923.7A CN114642629A (en) | 2022-03-22 | 2022-03-22 | Compound gel preparation and preparation method, administration mode and application thereof |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202210283923.7A CN114642629A (en) | 2022-03-22 | 2022-03-22 | Compound gel preparation and preparation method, administration mode and application thereof |
Publications (1)
Publication Number | Publication Date |
---|---|
CN114642629A true CN114642629A (en) | 2022-06-21 |
Family
ID=81996331
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202210283923.7A Pending CN114642629A (en) | 2022-03-22 | 2022-03-22 | Compound gel preparation and preparation method, administration mode and application thereof |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN114642629A (en) |
Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2710267A1 (en) * | 1993-07-12 | 1995-03-31 | Urso Michel | Composition for the treatment of male impotence |
EP1637149A1 (en) * | 2004-06-09 | 2006-03-22 | Medifood GmbH | Dietary supplement composition for the man |
CN106474155A (en) * | 2016-10-19 | 2017-03-08 | 天津普瑞赛尔生物科技有限公司 | External-use gel preparation containing human umbilical cord mesenchymal stem cells extract and its production and use |
CN109260246A (en) * | 2018-09-14 | 2019-01-25 | 俞晓彬 | A kind of Chinese herbs paste with treatment male sexual disfunction |
CN109893542A (en) * | 2018-04-04 | 2019-06-18 | 天津欣普赛尔生物医药科技有限公司 | Stem cell excretion body concentrate gel preparation for treating erectile dysfunction and preparation method thereof and medication |
CN109954001A (en) * | 2018-04-04 | 2019-07-02 | 天津欣普赛尔生物医药科技有限公司 | For treating the umbilical cord mesenchymal stem cells of erectile dysfunction and its combination formulations and preparation method and medication of excretion body |
-
2022
- 2022-03-22 CN CN202210283923.7A patent/CN114642629A/en active Pending
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2710267A1 (en) * | 1993-07-12 | 1995-03-31 | Urso Michel | Composition for the treatment of male impotence |
EP1637149A1 (en) * | 2004-06-09 | 2006-03-22 | Medifood GmbH | Dietary supplement composition for the man |
CN106474155A (en) * | 2016-10-19 | 2017-03-08 | 天津普瑞赛尔生物科技有限公司 | External-use gel preparation containing human umbilical cord mesenchymal stem cells extract and its production and use |
CN109893542A (en) * | 2018-04-04 | 2019-06-18 | 天津欣普赛尔生物医药科技有限公司 | Stem cell excretion body concentrate gel preparation for treating erectile dysfunction and preparation method thereof and medication |
CN109954001A (en) * | 2018-04-04 | 2019-07-02 | 天津欣普赛尔生物医药科技有限公司 | For treating the umbilical cord mesenchymal stem cells of erectile dysfunction and its combination formulations and preparation method and medication of excretion body |
CN109260246A (en) * | 2018-09-14 | 2019-01-25 | 俞晓彬 | A kind of Chinese herbs paste with treatment male sexual disfunction |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN109893542A (en) | Stem cell excretion body concentrate gel preparation for treating erectile dysfunction and preparation method thereof and medication | |
WO2016004212A1 (en) | Hydrogels for treating and ameliorating wounds and methods for making and using them | |
CN109954001A (en) | For treating the umbilical cord mesenchymal stem cells of erectile dysfunction and its combination formulations and preparation method and medication of excretion body | |
CN109908180A (en) | Endometrial stem cell excretion body concentrate gel preparation for treating endometrial impairment and preparation method thereof and medication | |
CN1181016A (en) | Use of hyaluronic acid for the treatment of interstitial cystitis | |
CN1785343A (en) | Ready prepared Chinese medicine for treating epicophosis and sonitus | |
CN117582402B (en) | Gel containing leukocyte extract and preparation method and application thereof | |
CN114712440A (en) | Dai medicine composition for relieving senile cutaneous pruritus and preparation and application thereof | |
CN108403628B (en) | Dexamethasone sodium phosphate injection | |
CN117327171B (en) | Modified recombinant humanized collagen and application thereof in vaginal dressing | |
CN111840525B (en) | Composition for treating thromboangiitis and preparation method thereof | |
CN114642629A (en) | Compound gel preparation and preparation method, administration mode and application thereof | |
CN114099547B (en) | Stem cell exosome preparation for skin repair | |
CN114681488A (en) | Preparation method and application of stem cell exosome concentrated solution gel preparation | |
RU2697059C1 (en) | Method of postoperative seroma treatment in patients with ventral hernias | |
CN114480271A (en) | Umbilical cord mesenchymal stem cell exosome for promoting healing of intractable pressure sores and preparation method thereof | |
CN101129632A (en) | Medicament with function of nourishing kidney, warming Yang, preserving essence and benefiting element and method of producing the same | |
CN114558107A (en) | Application of antibacterial peptide Cbf-14 in preparation of wound repair drugs | |
CN1772020A (en) | Freeze dried pubescent holly powder for injection and its prepn | |
CN113713176A (en) | Hydrogel and preparation method and application thereof | |
RU2306145C1 (en) | Preparation for treating chronic prostatitis | |
RU2803692C1 (en) | Method of treating gum recession using gingival tissue and regeneration stimulant preparation | |
RU2697196C1 (en) | Method of postoperative seroma treatment in patients with ventral hernias | |
WO2024108037A1 (en) | Equine-specific therapeutic compositions and methods of use | |
CN112220739B (en) | HPV virus inactivation dressing and preparation method thereof |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination |