CN111973549B - Bioadhesive hydrogel for treating gynecological inflammation - Google Patents

Bioadhesive hydrogel for treating gynecological inflammation Download PDF

Info

Publication number
CN111973549B
CN111973549B CN202010816678.2A CN202010816678A CN111973549B CN 111973549 B CN111973549 B CN 111973549B CN 202010816678 A CN202010816678 A CN 202010816678A CN 111973549 B CN111973549 B CN 111973549B
Authority
CN
China
Prior art keywords
hydrogel
nitric oxide
poloxamer
heparin
inflammation
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.)
Active
Application number
CN202010816678.2A
Other languages
Chinese (zh)
Other versions
CN111973549A (en
Inventor
赵应征
鲁翠涛
姚情
徐荷林
翟媛媛
杜楚楚
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Wenzhou Medical University
Original Assignee
Wenzhou Medical University
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Wenzhou Medical University filed Critical Wenzhou Medical University
Priority to CN202010816678.2A priority Critical patent/CN111973549B/en
Publication of CN111973549A publication Critical patent/CN111973549A/en
Application granted granted Critical
Publication of CN111973549B publication Critical patent/CN111973549B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

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
    • A61K9/0012—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
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/18—Growth factors; Growth regulators
    • A61K38/1808—Epidermal growth factor [EGF] urogastrone
    • 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
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The bioadhesive hydrogel for treating gynecological inflammation comprises a hydrogel matrix and nitric oxide nanobubbles, wherein the nitric oxide nanobubbles are uniformly dispersed in the hydrogel matrix. The hydrogel matrix consists of heparin-poloxamer, chitosan quaternary ammonium salt and epidermal cell growth factor, wherein the mass ratio of the heparin-poloxamer to the chitosan quaternary ammonium salt is 1-5:10, and the molar mass of the epidermal cell growth factor is equal to 50% of that of the heparin-poloxamer. The nanometer nitric oxide bubble consists of yolk phospholipid and poloxamer as bubble membrane material and the yolk phospholipid and poloxamer are coated with nitric oxide gas in the weight ratio of 1 to 25, particle size of 500-900 nm and concentration of 6 x 10 7 ～9×10 7 And each mL. The hydrogel is infused into the genital cavity and is used for treating gynecological genital system inflammation.

Description

Bioadhesive hydrogel for treating gynecological inflammation
Technical Field
The application relates to a medicinal preparation for treating gynecological genital system inflammation, in particular to a bioadhesive hydrogel for treating gynecological genital system inflammation.
Background
Gynecological inflammation of the reproductive system is the most common disease of gynecology, such as colpitis, endometritis and the like, and can occur in all age groups, and the damage of the gynecological inflammation is very serious, such as the influence on the quality of life and the female infertility. After female suffering from gynecological genital system inflammation, symptoms such as leucorrhea increase, pruritus vulvae and the like can appear, and the normal life of female is seriously affected. Women may have a significant impact on fetal development during pregnancy, particularly when they are given birth, and may also transmit disease to the fetus, affecting fetal health.
It is found that nitric oxide has a good therapeutic effect on inflammation. Animal experiments of an inflammation model show that nitric oxide mainly plays an anti-inflammatory role in the early stage of inflammation, and the specific roles comprise: maintaining microcirculation integrity, relaxing vascular smooth muscle, increasing intestinal mucosa blood flow, inhibiting adhesion and accumulation of blood platelet and leukocyte on endothelial cell surface, preventing thrombosis, inhibiting myeloperoxidase activity, protecting epithelial barrier, and promoting epithelial tissue repair. However, in the late stage of inflammation, with the production of superoxide anion oxygen, nitric oxide can be synthesized with anion oxygen to produce peroxynitrite, and the biological oxidability of the nitric oxide can cause damage to normal tissues.
Nitric oxide plays a dual role in the development process of gynecological genital system inflammation, and has the functions of protecting mucous membrane of the genital system and killing sperms to cause infertility. In the environment of the anoxia genital tract, nitric oxide molecules mainly exert anti-inflammatory and protective effects. Methods for supplementing nitric oxide in vivo have been reported to employ nitric oxide donor compounds. Nitric oxide donor compounds fall into two categories: non-enzymatic and enzymatic forms. The non-enzymatic nitric oxide donor compound is mostly from nitro compounds, including nitroprusside, organic or inorganic nitrite and nitrate, nitrosamine, nitrogen mustard, hydrazine, etc., and has small dosage and large toxic and side effects. Whereas enzymatic nitric oxide donor compounds (e.g. arginine) require the generation of nitric oxide molecules by decomposition of the compound by biological enzymes in the body, etc. The nitric oxide molecules generated by the nitric oxide donor compounds cannot be concentrated in the genital tract to play a role, so that the effect of treating the genital system inflammation by using the nitric oxide donor compounds is poor.
The nitric oxide molecules are in the form of a gas, and nitric oxide gas (NO) is slightly soluble in water, and has a solubility of only 5.6X10 in water at 20 DEG C -3 g/L (equivalent to 0.186 mu mol/L) can not be prepared into common dosage forms, and can play an anti-inflammatory role of the reproductive system.
In situ gels are a class of formulations that, upon administration in solution, undergo a phase transition at the site of administration, from a liquid state to a non-chemically crosslinked semi-solid gel. The gel has good tissue compatibility and long retention time at the administration position; meanwhile, the medicine can be stored, and the medicine is prevented from being influenced by the environment and the like. In situ gels can be classified into temperature-sensitive, pH-sensitive, ion-sensitive, and the like, depending on the mechanism of formation. The in-situ gel is used as a novel drug dosage form, is widely applied to novel drug delivery systems such as slow release, controlled release, pulse release and the like, can be applied to various routes of drug delivery such as skin, eyes, nasal cavities, oral cavities, vaginas, rectum and the like, and becomes a research hot spot in the fields of pharmacy and biotechnology.
While in situ gels have a number of advantages in genital tract administration and topical treatments, nitric oxide is a gas and no research has been reported to efficiently carry nitric oxide gas into in situ gels. Thus, preparing an in situ gel that efficiently carries nitric oxide gas is a limiting bottleneck in developing nitric oxide to treat inflammation of the reproductive system.
Disclosure of Invention
The application aims to overcome the defects of the prior art (namely, lack of in-situ gel for efficiently carrying nitric oxide gas) and provide a medicine gel for local effect of a genital cavity, which provides maximum guarantee for guaranteeing the curative effect of genital system inflammation and meets the requirements of clinical treatment on safety, effectiveness, convenience and economy.
The inventors have found that epidermal growth factor and nitric oxide molecules can produce a synergistic effect in the treatment of inflammation of the reproductive system. The nitrogen monoxide nanobubble formed by wrapping nitrogen monoxide gas with egg yolk phospholipid and poloxamer as bubble membrane material can convert the nitrogen monoxide gas into liquid. Heparin-poloxamer not only has good temperature-sensitive hydrogel property, but also has high affinity of yolk phospholipids and high carrying capacity of epidermal cell growth factors. Both the heparin-poloxamer and the chitosan have the functions of resisting bacteria, diminishing inflammation, improving immunity, stopping bleeding, relieving pain, promoting repair and regeneration of damaged tissues, inhibiting scar formation and the like. However, how to organically combine the beneficial factors of nitric oxide, epidermal cell growth factor, heparin-poloxamer and chitosan and exert the synergistic treatment effect of the inflammation of the reproductive system is not reported.
Through a large number of experiments, the inventor obtains a bioadhesive hydrogel capable of locally acting in a genital tract to treat gynecological inflammation, wherein the hydrogel comprises a hydrogel matrix and nitric oxide nanobubbles, and the nitric oxide nanobubbles are uniformly dispersed in the hydrogel matrix.
The hydrogel matrix consists of heparin-poloxamer, chitosan quaternary ammonium salt and epidermal cell growth factor, wherein the mass ratio of the heparin-poloxamer to the chitosan quaternary ammonium salt is 1-5:10, and the molar mass of the epidermal cell growth factor is equal to 50% of that of the heparin-poloxamer.
The preferable mass ratio of the heparin-poloxamer to the chitosan quaternary ammonium salt in the hydrogel matrix is 2-3:10.
The hydrogel matrix is further added with the following components: sugar, electrolyte salt, amino acid, pH buffer and antioxidant.
The nitric oxide nanobubble is composed of a vesicle formed by wrapping nitric oxide gas by taking egg yolk phospholipid and poloxamer as a bubble membrane material.
The particle size of the nitric oxide nanobubble is 500-900 nm.
The concentration of the nitric oxide nanobubble in the nitric oxide in-situ hydrogel is 6 multiplied by 10 7 ～9×10 7 And each mL.
The preparation method of the bioadhesive hydrogel for treating gynecological inflammation is characterized by comprising the following steps:
a: dispersing heparin-poloxamer and chitosan quaternary ammonium salt in 6 times of 8 ℃ water for injection, placing the mixture in a refrigerator at 4-8 ℃ for overnight, slowly dissolving, adding epidermal cell growth factor, and uniformly mixing to form hydrogel matrix solution;
b: mixing yolk phospholipids and poloxamer in a mass ratio of 1:25, dissolving in anhydrous tertiary butanol with a mass of 10 times of 65 ℃, slowly cooling to solidify the solution, standing overnight at-10 ℃, freeze-drying to obtain loose freeze-dried powder, transferring into a bottle with a plug, filling nitric oxide gas to saturation, adding into water for injection with a mass of 5 times of the freeze-dried powder, and uniformly mixing to form a nitric oxide nano bubble solution;
c: adding the nitric oxide nanobubble solution prepared in the step b into the hydrogel matrix solution prepared in the step a at 10 ℃ until the concentration of the nitric oxide nanobubbles in the hydrogel is 6 multiplied by 10 7 ～9×10 7 Mixing with small amount of water at a ratio of one mL, and sealing and preserving at 10deg.C;
d: the bioadhesive hydrogel solution for treating gynecological inflammation prepared in the step c is exposed to the environment of 30-37 ℃ to rapidly gel to form semisolid hydrogel.
The preparation method of the bioadhesive hydrogel for treating gynecological genital system inflammation is characterized by comprising the following steps: the hydrogel matrix is further added with: sugar, electrolyte salt, amino acid, pH buffer and antioxidant.
The hydrogel is infused into genital tract, and can be used for treating gynecological inflammation.
The bioadhesive hydrogel for treating gynecological inflammation has the following advantages: (1) the beneficial components of nitric oxide, epidermal cell growth factor, heparin-poloxamer and chitosan are organically combined to play a synergistic treatment role of the inflammation of the reproductive system; (2) has the functions of biological adhesion and slow release and long-acting, and has good affinity and biocompatibility on epithelial mucosa of genital cavity; (3) no nitric oxide donor compound is used, and adverse reaction and toxic and side effects on body tissues caused by the nitric oxide donor compound are avoided; (4) convenient to use, and immediately takes a gel state after being poured into the genital cavity, thereby realizing the purpose of long-acting treatment of gynecological genital system inflammation.
Detailed Description
Hereinafter, specific embodiments of the present application will be described in detail. It should be noted that the technical features or combinations of technical features described in the following embodiments should not be regarded as being isolated, and they may be combined with each other to achieve a better technical effect.
Example 1 preparation of bioadhesive hydrogels for the treatment of gynecological inflammation
The bioadhesive hydrogels of the experimental group were prepared according to the component ratios of table 1, specifically comprising the following steps:
a: dispersing heparin-poloxamer and chitosan quaternary ammonium salt in 6 times of 8 ℃ injection water, placing the mixture in a refrigerator at 4-8 ℃ for overnight, slowly dissolving, adding epidermal cell growth factor with the molar mass equal to 50% of that of the heparin-poloxamer, and uniformly mixing to form hydrogel matrix solution;
b: mixing yolk phospholipids and poloxamer in a mass ratio of 1:25, dissolving in anhydrous tertiary butanol with a mass of 10 times of 65 ℃, slowly cooling to solidify the solution, standing overnight at-10 ℃, freeze-drying to obtain loose freeze-dried powder, transferring into a bottle with a plug, filling nitric oxide gas to saturation, adding into water for injection with a mass of 5 times of the freeze-dried powder, and uniformly mixing to form a nitric oxide nano bubble solution;
c: adding the nitric oxide nanobubble solution prepared in the step b into the hydrogel matrix solution prepared in the step a at 10 ℃, adjusting the concentration of the nitric oxide nanobubbles in the hydrogel according to the design of the table 1, mixing the nitric oxide nanobubbles with the hydrogel, preparing the nitric oxide in-situ hydrogel solution, and preserving the nitric oxide in a sealed environment at 10 ℃ to obtain the bioadhesive hydrogel.
Hydrogels of the control group were prepared according to the component ratios of table 1 with reference to the experimental group. Each experimental group is configured according to the components and proportions within the scope of the claims of the present application, and each control group is a component lacking or having a component mass percentage that is outside the scope of the claims of the present application.
Table 1 composition of bioadhesive hydrogels of experimental and control groups
Note that: "v" represents the concentration and method of the experimental group of example 1;"/" indicates that the term is absent; * Representing that the component is replaced by a component in brackets; TGF-alpha represents transforming growth factor-alpha; NO represents nitric oxide gas; o (O) 2 Represents oxygen; n (N) 2 Representing nitrogen.
Example 2 application Effect of bioadhesive hydrogels for treating gynecological inflammation
(1) Establishment of animal model of genital inflammation
Reference [ construction of animal model of rat genital tract inflammation. Journal of Sichuan physiological science, 2007, 29 (001): 1-3, constructing a rat vaginitis animal model by using phenol cement. The method is briefly described as follows: bilateral rat ovaries were excised, oestradiol benzoate and hydrocortisone were injected to cause pseudo estrus and general immune dysfunction, then 0.1mL of phenol cement was injected into the vagina of each rat, 3 times a day apart, vulva changes were observed and recorded daily, after 15 th day of postoperative weighing, the eyeballs were bled, and the total number of white blood cells was determined by microscopic counting. When the total number of white blood cells of the rat is obviously increased, the vaginal orifice is red and swollen with pus outflow, and the modeling is determined to be successful.
(2) Effect of each group of hydrogels in treating vaginitis
Rats with successful vaginitis modeling are selected, the rats are equally divided into a plurality of groups according to the design of a table 1, 100 mu L of hydrogel is infused into the vagina in 1, 3, 5, 7 and 9 days, the vulva change is recorded in 14 days of conventional feeding, blood is taken from eyeballs, the total number of white blood cells is measured by a microscopic counting method, the neck is broken, the vagina tissue is taken for pathological examination. The pathophysiological condition of the vagina, especially whether the epithelial cells of the mucous membrane of the vagina are denatured and necrotized, whether ulcers are formed in the vagina or not, and the like are observed through histological staining, and the effect of each group of hydrogel on treating vaginitis is evaluated.
The evaluation results of the groups are shown in Table 2, and the total scores of the application effects of the hydrogels of the groups are given by integrating the evaluation indexes.
Table 2 effects of bioadhesive hydrogels in experimental and control groups for the treatment of vaginitis
As can be seen from the experimental results in Table 2, the bioadhesive hydrogel of the experimental group has good therapeutic effect on vaginitis, particularly the experimental group 6 has normal rat vulva morphology, the total number of white blood cells is close to the normal value, the epithelial cells of the vaginal mucosa are close to the normal value, and the therapeutic effect on vaginitis is good. Compared with the experimental group, the hydrogel of the control group has obviously poorer treatment effect on vaginitis, in particular to the control groups 1, 2, 3, 14 and 15, the rat vulva has obviously red and swollen, the total number of white blood cells is obviously increased, the epithelial cells of the vaginal mucosa are denatured and necrotized, the vagina has obvious ulcer, and the treatment effect on vaginitis is poor.
The experimental results in table 2 prove that any component and condition in the technical protection scheme of the application are mutually synergistic and indispensable, and the lack of any component and condition in the technical protection scheme of the application can obviously influence the treatment effect of the inflammation of the reproductive system. The bioadhesive hydrogel organically combines the beneficial factors of nitric oxide, epidermal cell growth factor, heparin-poloxamer and chitosan, plays a role in synergic treatment of gynecological genital system inflammation, and has good application prospect.
The foregoing detailed description is directed to embodiments of the application which are not intended to limit the scope of the application, but rather to cover all modifications and variations within the scope of the application. Further, various modifications, additions and substitutions in other forms and details may be made by those skilled in the art within the scope and spirit of the application as disclosed in the accompanying claims. Of course, such modifications, additions and substitutions are intended to be included within the scope of the application as set forth in the accompanying claims.

Claims (8)

1. A bioadhesive hydrogel for treating inflammation of the gynaecological reproductive system, characterized in that: the hydrogel bagThe nitric oxide nano-bubbles are uniformly dispersed in the hydrogel matrix; the hydrogel matrix consists of heparin-poloxamer, chitosan quaternary ammonium salt and epidermal cell growth factor, wherein the mass ratio of the heparin-poloxamer to the chitosan quaternary ammonium salt is 1-5:10, and the molar mass of the epidermal cell growth factor is equal to 50% of that of the heparin-poloxamer; the nitric oxide nanobubble is composed of a vesicle formed by wrapping nitric oxide gas by taking egg yolk phospholipid and poloxamer as bubble membrane materials, wherein the mass ratio of the egg yolk phospholipid to the poloxamer is 1:25; the particle size range of the nitric oxide nanobubble is 500-900 nm; the concentration of the nitric oxide nanobubble in the nitric oxide in-situ hydrogel is 6 multiplied by 10 7 ～9×10 7 individual/mL; the hydrogel is infused into genital cavity and is used for treating gynecological genital system inflammation.
2. The hydrogel of claim 1, characterized in that: the mass ratio of the heparin-poloxamer to the chitosan quaternary ammonium salt in the hydrogel matrix is 2-3:10, and the molar mass of the epidermal cell growth factor is equal to 50% of that of the heparin-poloxamer.
3. The hydrogel of claim 1, characterized in that: the hydrogel matrix is further added with: sugar, electrolyte salt, amino acid, pH buffer and antioxidant.
4. The hydrogel of claim 1, characterized in that: the particle size of the nitric oxide nanobubble is 700nm.
5. The hydrogel of claim 1, characterized in that: the concentration of the nitric oxide nanobubble in the nitric oxide in-situ hydrogel is 7.5X10 7 And each mL.
6. A method of preparing the hydrogel of claim 1, comprising: the method comprises the following steps:
a: dispersing heparin-poloxamer and chitosan quaternary ammonium salt in 6 times of 8 ℃ water for injection, placing the mixture in a refrigerator at 4-8 ℃ for overnight, slowly dissolving, adding epidermal cell growth factor, and uniformly mixing to form hydrogel matrix solution;
b: mixing yolk phospholipids and poloxamer in a mass ratio of 1:25, dissolving in anhydrous tertiary butanol with a mass of 10 times of that of 65 ℃, slowly cooling to solidify the solution, standing overnight at-10 ℃, freeze-drying to obtain loose freeze-dried powder, transferring into a bottle with a plug, filling nitric oxide gas to saturation, adding into water for injection with a mass of 5 times of that of the freeze-dried powder, and uniformly mixing to form a nitric oxide nanobubble solution;
c: adding the nitric oxide nanobubble solution prepared in the step b into the hydrogel matrix solution prepared in the step a at 10 ℃ until the concentration of the nitric oxide nanobubbles in the hydrogel is 6 multiplied by 10 7 ～9×10 7 Mixing with small amount of water at a ratio of one mL, and sealing and preserving at 10deg.C;
d: the bioadhesive hydrogel solution for treating gynecological inflammation prepared in the step c is exposed to the environment of 30-37 ℃ to rapidly gel to form semisolid hydrogel.
7. The method for producing a hydrogel according to claim 6, characterized in that: the hydrogel matrix is further added with: sugar, electrolyte salt, amino acid, pH buffer and antioxidant.
8. The method for producing a hydrogel according to claim 6, characterized in that: the hydrogel is infused into genital cavity and is used for treating gynecological genital system inflammation.
CN202010816678.2A 2020-08-06 2020-08-06 Bioadhesive hydrogel for treating gynecological inflammation Active CN111973549B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202010816678.2A CN111973549B (en) 2020-08-06 2020-08-06 Bioadhesive hydrogel for treating gynecological inflammation

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202010816678.2A CN111973549B (en) 2020-08-06 2020-08-06 Bioadhesive hydrogel for treating gynecological inflammation

Publications (2)

Publication Number Publication Date
CN111973549A CN111973549A (en) 2020-11-24
CN111973549B true CN111973549B (en) 2023-08-25

Family

ID=73434414

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202010816678.2A Active CN111973549B (en) 2020-08-06 2020-08-06 Bioadhesive hydrogel for treating gynecological inflammation

Country Status (1)

Country Link
CN (1) CN111973549B (en)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111919835B (en) * 2020-08-06 2022-02-08 温州医科大学 Preservation solution for maintaining activity of red blood cells
CN114558114B (en) * 2022-03-31 2023-10-20 温州医科大学 Emulsion type spray for treating pressure sores

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109276577A (en) * 2018-11-01 2019-01-29 重庆大学 A kind of nitric oxide Nanometer composite hydrogel and its preparation method and application

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8871259B2 (en) * 2012-09-19 2014-10-28 Transdermal Biotechnology, Inc. Techniques and systems for treatment of neuropathic pain and other indications
US20190328660A1 (en) * 2018-04-26 2019-10-31 Zvi Yaniv Nanobubbles in an absorbent material

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109276577A (en) * 2018-11-01 2019-01-29 重庆大学 A kind of nitric oxide Nanometer composite hydrogel and its preparation method and application

Also Published As

Publication number Publication date
CN111973549A (en) 2020-11-24

Similar Documents

Publication Publication Date Title
AU2000250426B2 (en) Systems and methods for topical treatment with nitric oxide
CN111973549B (en) Bioadhesive hydrogel for treating gynecological inflammation
ES2200008T3 (en) FOAMABLE FORMULATION AND FOAM.
ES2482190T3 (en) Use of lactic acid oligomers in the treatment of gynecological infections
BRPI9809725B1 (en) composition and device for treating an injury
ES2664951T3 (en) Compositions comprising low viscosity glycosaminoglycans and use of said composition in chronic cystitis therapy
CN102525884A (en) Thermosensitive in-situ gel preparation for vaginal administration
EA014391B1 (en) Pharmaceutical composition for treating burns and a method for the production thereof
CN111956600B (en) Nitric oxide in situ hydrogel for treating colonitis
WO2017215610A1 (en) Efficient and safe chitosan derivative-based disinfectant and preparation method therefor
CN101972470A (en) In-situ gel composition for eyes
KR0163563B1 (en) Topical drug in combination for treatment of skin lesions
CN101683316B (en) Temperature responsive bio-adhesive in situ gel sustained-release preparation for vagina
Liu et al. A novel nitric oxide-releasing gel for diabetic wounds
CN101972224B (en) Eye in-situ gel
EP3153156A1 (en) Composition based on a stabilized solution of active ingredients
JP7454288B2 (en) Method for preparing a novel veterinary uterine injection
CN111973550B (en) Nitric oxide in situ hydrogel for treating osteoarthritis
WO2019241985A1 (en) Hydrogel, pharmaceutical composition comprising same, and application thereof
CN106309354A (en) Nasal-delivery temperature-sensitive in-situ gel sustained-release preparation comprising ketorolac tromethamine
CN109646671A (en) A kind of growth-factor preparation and its preparation method and application
CN111920761B (en) In situ hydrogel for treating chronic muscle and soft tissue soreness
CN109646392A (en) A kind of gelling agent and its preparation process containing clindamycin phosphate
CN111956812B (en) Pharmaceutical preparation for ultrasonic diagnosis and treatment of gastritis
Grebeniuk et al. Evaluation of the effect of excess and deficiency of serum hydrogen sulfide on the condition of the vaginal wall of intact rats

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
GR01 Patent grant
GR01 Patent grant