Exosome gynecological gel soft capsule and production process thereof

Abstract

The invention discloses an exosome gynecological gel soft capsule and a production process, the exosome gynecological gel soft capsule comprises a core active component, an auxiliary material and purified water, the core active component is exosome, the auxiliary material comprises a gel matrix, a humectant, a stabilizer, a bacteriostatic agent, a pH regulator and a thickening agent, the gel matrix comprises a water-soluble matrix and a fat-soluble matrix, and the water-soluble matrix comprises a water-soluble matrix and a fat-soluble matrix. The water-soluble matrix comprises hydroxypropyl methyl cellulose (HPMC), Carbomer and sodium alginate, the fat-soluble matrix comprises a glycerol gelatin and polyethylene glycol (PEG) composite matrix, the humectant comprises glycerol and hyaluronic acid, the stabilizer comprises trehalose and mannitol, and the water-soluble matrix comprises sodium alginate and sodium alginate. The exosome gynecological gel soft capsule is a novel biological preparation combining a stem cell exosome technology and gynecological treatment, has the effect based on the multi-target regulation and control capability of the exosome, and can improve gynecological problems through various mechanisms such as tissue repair, microenvironment regulation and inflammation inhibition.

Description

TECHNICAL FIELD

[0001] The application relates to a capsule and a production method thereof, in particular to an exosome gynecological gel soft capsule and a production process. BACKGROUND

[0002] Gynecology is a branch of obstetrics and gynecology, which is a professional department mainly for the diagnosis and treatment of female gynecological diseases, and is divided into western medicine gynecology and traditional Chinese medicine gynecology. Diseases of the female reproductive system are gynecological diseases, including external genital disease, vaginal disease, uterine disease, etc. which can be used for external treatment. The subject of medicine is women's diseases, such as gynecology. Or refers to a department in a hospital that specializes in treating women's diseases. Diseases of the female reproductive system are called gynecological diseases. There are many types of gynecological diseases, the most common of which are uterine fibroids, ovarian cysts, vaginitis, cervicitis, cervical erosion, pelvic inflammatory disease, adnexitis, functional uterine bleeding, breast disease, infertility, irregular menstruation, endometritis, abnormal leukorrhea, etc. Women should understand some basic medical knowledge such as menstruation, fertility, pregnancy, childbirth and menopause from youth, and often maintain an optimistic mood, which can avoid or reduce the occurrence of some gynecological diseases;

[0003] Exosomes can activate cell surface receptors through protein ligands and bioactive lipids, or participate in cell regulation and physiological and pathological processes by fusing the goods (such as proteins or iRNA) they transport into the cytoplasmic membrane. More and more evidence shows that EVs are important mediators of intercellular communication, and therefore they play an important role in physiological and pathological processes such as stem cell maintenance, tissue repair, immune regulation and tumor growth;

[0004] In order to assist the treatment of mild to moderate vaginal inflammation (such as bacterial vaginitis and vulvovaginal candidiasis), repair cervical mucosa damage, repair the wound after gynecological surgery (such as cervical conization and laser treatment), improve the vaginal microenvironment and promote the recovery of mucosal barrier function, the application designs an exosome gynecological gel soft capsule and a production process. SUMMARY

[0005] The purpose of the application is to provide an exosome gynecological gel soft capsule and a production process to solve the problems in the background art.

[0006] To achieve the above purpose, the application provides the following technical scheme:

[0007] An exosome gynecological gel soft capsule, which comprises core active ingredients, excipients and purified water, wherein the core active ingredients are exosomes, and the excipients comprise a gel matrix, a humectant, a stabilizer, a bacteriostatic agent, a pH regulator and a thickening agent.

[0008] As a further scheme of the present application: the gel matrix comprises a water-soluble matrix and a fat-soluble matrix.

[0009] As a further scheme of the present application: the water-soluble matrix comprises hydroxypropyl methyl cellulose (HPMC), carbomer and sodium alginate, and the fat-soluble matrix comprises glycerol gelatin and polyethylene glycol (PEG) complex matrix.

[0010] As a further scheme of the present application: the humectant comprises glycerol and hyaluronic acid.

[0011] As a further scheme of the present application: the stabilizer comprises trehalose and mannitol.

[0012] As a further scheme of the present application: the bacteriostatic agent comprises phenoxyethanol and parabens.

[0013] As a further scheme of the present application: the pH regulator comprises lactic acid and citric acid.

[0014] As a further scheme of the present application: the thickening agent comprises xanthan gum and polyvinylpyrrolidone (PVP).

[0015] The production process of the exosome gynecological gel soft capsule is as follows:

[0016] Step one: exosome preparation;

[0017] Mesenchymal stem cell culture supernatant is used to extract exosomes, which are separated and purified by ultracentrifugation or kit method. After separation and purification, the exosomes need to be freeze-dried for preservation. The freeze-dried preservation needs to verify the activity retention rate.

[0018] Step two: gel matrix preparation;

[0019] Hydroxypropyl methyl cellulose is dispersed in purified water, and after swelling, glycerol, sodium hyaluronate and trehalose are added and uniformly mixed.

[0020] Further use lactic acid to adjust pH to 4.0-4.5, further sterilization treatment, sterilization methods include moist heat sterilization or filtration sterilization;

[0021] Step three: exosome loading;

[0022] The freeze-dried exosomes are reconstituted in sterile buffer, and further mixed with the gel matrix at low temperature, avoiding the generation of bubbles;

[0023] Step four: filling and packaging;

[0024] Soft capsule filling equipment is used to fill the gel into gelatin or plant-derived capsule shells (such as hydroxypropyl starch capsules), and the packaging process needs to be carried out in a sterile environment.

[0025] Step 5: Drying and packaging;

[0026] After filling and packaging, low-temperature drying is further used to remove excess moisture, and aluminum-plastic packaging is used to protect against light and moisture.

[0027] Compared with the prior art, the present invention has the following beneficial effects:

[0028] The exosome gynecological gel soft capsule of the present invention is a new biological preparation that combines stem cell exosome technology with gynecological treatment. Its efficacy is based on the multi-target regulation ability of exosomes, and can improve gynecological problems through multiple mechanisms such as repairing tissues, regulating the microenvironment, and inhibiting inflammation. BRIEF DESCRIPTION OF THE DRAWINGS

[0029] Figure 1 The figure is a flow chart of the method steps for the production process of exosome gynecological gel soft capsules. DETAILED DESCRIPTION

[0030] The following will clearly and completely describe the technical solutions in the embodiments of the present invention in conjunction with the accompanying drawings. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative efforts are within the scope of protection of the present invention.

[0031] See also Figure 1In an embodiment of the present invention, an exosome gynecological gel soft capsule comprises a core active ingredient, excipients and purified water, wherein the core active ingredient is exosomes, such as exosomes derived from mesenchymal stem cells, which are used for anti-inflammatory, mucosal repair, immune regulation and cell regeneration promotion. Each exosome gynecological gel soft capsule contains 10-50 μg of exosomes (specific amount needs to be optimized based on in vitro experiments and clinical data), the excipients include a gel matrix, a moisturizer, a stabilizer, an antibacterial agent, a pH regulator and a thickener, the gel matrix includes a water-soluble matrix and a fat-soluble matrix, and the water-soluble matrix includes hydroxypropyl methylcellulose ( HPMC), carbomer and sodium alginate, the water-soluble matrix is ​​used for sustained and controlled release, the fat-soluble matrix includes a glycerol gelatin and polyethylene glycol (PEG) composite matrix, the moisturizer includes glycerol and hyaluronic acid, the moisturizer is used to enhance mucosal adhesion, the stabilizer includes trehalose and mannitol, the stabilizer is used to protect exosome activity, the antibacterial agent includes phenoxyethanol and parabens, the antibacterial agent needs to comply with the safety standards of vaginal preparations, the pH regulator includes lactic acid and citric acid, the pH regulator is used to maintain the weak acidic environment of the vagina, and the weak acidic environment of the vagina is maintained at pH 3.8-4.5, the thickener includes xanthan gum and polyvinylpyrrolidone (PVP), and the weight proportions of the components are as follows: 0.1-0.5 parts of exosomes, 5-8 parts of hydroxypropyl methylcellulose, 0.5-1 parts of sodium hyaluronate, 10-15 parts of glycerol, 2-3 parts of trehalose, 0.1-0.3 parts of phenoxyethanol, a certain amount of lactic acid and purified water;

[0032] The production process of exosome gynecological gel soft capsules is as follows:

[0033] Step 1: Exosome preparation;

[0034] Exosomes are extracted from the culture supernatant of mesenchymal stem cells and separated and purified using ultracentrifugation or a kit. After separation and purification, they need to be freeze-dried and stored. The activity retention rate needs to be verified during freeze-dried storage.

[0035] Step 2: Gel matrix preparation;

[0036] Disperse hydroxypropyl methylcellulose in purified water, add glycerol, sodium hyaluronate and trehalose after swelling, and mix homogeneously;

[0037] The pH is further adjusted to 4.0-4.5 using lactic acid, and the mixture is further sterilized by moist heat sterilization or filtration sterilization;

[0038] Step 3: exosome loading;

[0039] Redissolve the lyophilized exosomes in sterile buffer (e.g., PBS) and gently mix with the gel matrix at low temperature (2-8°C) to avoid the formation of bubbles.

[0040] Step 4: Filling and packaging;

[0041] Use soft capsule filling equipment to fill the gel into gelatin or plant-derived capsule shells (such as hydroxypropyl starch capsules). The encapsulation process must be carried out in a sterile environment (Class C clean area);

[0042] Step 5: Drying and packaging;

[0043] After filling and packaging, low-temperature drying is further used to remove excess moisture (humidity < 20%), and aluminum-plastic packaging is used to avoid light and moisture.

[0044] Exosome Gynecological Gel Soft Capsules are suitable for:

[0045] 1. Adjuvant treatment of mild to moderate vaginal inflammation (such as bacterial vaginosis and vulvovaginal candidiasis);

[0046] 2. Repair of cervical mucosal damage;

[0047] 3. Wound repair after gynecological surgery (such as cervical conization, laser treatment);

[0048] 4. Improve the vaginal microenvironment and promote the recovery of mucosal barrier function;

[0049] The method of using the exosome gynecological gel soft capsule of the present invention is as follows:

[0050] For vaginal administration:

[0051] Step 1: Preparation before use: Clean your hands and vulva. It is recommended to use before going to bed;

[0052] Step 2: Take out the soft capsule and tear open the aluminum-plastic packaging; lie on your back with your knees bent, and gently push the soft capsule deep into the vagina (about one finger deep). It is recommended to take one soft capsule once a day for 7-10 days or as directed by your doctor.

[0053] Things to note are as follows:

[0054] Avoid getting up immediately after use. It is recommended to rest in bed for 30 minutes.

[0055] Stop using during menstruation;

[0056] If combined with other vaginal preparations, at least 2 hours should be allowed.

[0057] Quality Control:

[0058] 1. Exosome activity detection: Verify integrity through nanoparticle tracking analysis (NTA) and Western blot (CD63 / TSG101 labeling).

[0059] 2. Microbial limits: Meet the requirements of vaginal preparations in the Chinese Pharmacopoeia (aerobic bacteria, molds, and yeasts ≤ 10 CFU / g).

[0060] 3. Release rate: The vaginal environment was simulated in vitro (e.g., dissolution medium pH 4.5) to measure the exosome sustained-release curve.

[0061] 4. Stability: Accelerated test (40°C / 75% RH) for 6 months, long-term stability (25°C) to monitor the active ingredient retention rate.

[0062] Although the present invention has been described in detail with reference to the aforementioned embodiments, it is still possible for those skilled in the art to modify the technical solutions described in the aforementioned embodiments, or to make equivalent substitutions for some of the technical features therein. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention should be included in the scope of protection of the present invention.

Claims

1. An exosome gynecological gel soft capsule, characterized by: Its components include core active ingredients, excipients and purified water. The core active ingredient is exosomes. The excipients include gel matrix, moisturizer, stabilizer, antibacterial agent, pH regulator and thickener.

2. The exosome gynecological gel soft capsule according to claim 1, characterized in that: The gel matrix includes a water-soluble matrix and a fat-soluble matrix.

3. The exosome gynecological gel soft capsule according to claim 2, characterized in that: The water-soluble matrix includes hydroxypropyl methylcellulose (HPMC), carbomer and sodium alginate, and the fat-soluble matrix includes a glycerol gelatin and polyethylene glycol (PEG) composite matrix.

4. The exosome gynecological gel soft capsule according to claim 1, characterized in that: The moisturizers include glycerin and hyaluronic acid.

5. The exosome gynecological gel soft capsule according to claim 1, characterized in that: The stabilizers include trehalose and mannitol.

6. The exosome gynecological gel soft capsule according to claim 1, characterized in that: The antibacterial agents include phenoxyethanol and parabens.

7. The exosome gynecological gel soft capsule according to claim 1, characterized in that: The pH adjusters include lactic acid and citric acid.

8. The exosome gynecological gel soft capsule according to claim 1, characterized in that: The thickeners include xanthan gum and polyvinylpyrrolidone (PVP).

9. The production process of the exosome gynecological gel soft capsule according to claim 1, characterized in that: The production method steps are as follows: Step 1: Exosome preparation; Exosomes are extracted from the culture supernatant of mesenchymal stem cells and separated and purified using ultracentrifugation or a kit. After separation and purification, they need to be freeze-dried and stored. The activity retention rate needs to be verified during freeze-dried storage. Step 2: Gel matrix preparation; Disperse hydroxypropyl methylcellulose in purified water, add glycerol, sodium hyaluronate and trehalose after swelling, and mix homogeneously; The pH is further adjusted to 4.0-4.5 using lactic acid, and the mixture is further sterilized by moist heat sterilization or filtration sterilization; Step 3: exosome loading; The lyophilized exosomes were reconstituted in sterile buffer and further mixed with the gel matrix gently at low temperature to avoid the formation of bubbles; Step 4: Filling and packaging; Use soft capsule filling equipment to fill the gelatin or plant-derived capsule shells. The encapsulation process must be carried out under a sterile environment. Step 5: Drying and packaging; After filling and packaging, low-temperature drying is further used to remove excess moisture, and aluminum-plastic packaging is used to protect against light and moisture.

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