CN110882211A - Hydroxyphenyl ester gel and preparation method thereof - Google Patents

Hydroxyphenyl ester gel and preparation method thereof Download PDF

Info

Publication number
CN110882211A
CN110882211A CN201911414584.6A CN201911414584A CN110882211A CN 110882211 A CN110882211 A CN 110882211A CN 201911414584 A CN201911414584 A CN 201911414584A CN 110882211 A CN110882211 A CN 110882211A
Authority
CN
China
Prior art keywords
gel
hydroxyphenyl
carbomer
hydroxyphenyl ester
bacteriostatic agent
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
Application number
CN201911414584.6A
Other languages
Chinese (zh)
Inventor
郑招荣
梁灿丽
柳秋月
蔡佳龙
刘金超
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.)
Shenzhen Hansen Standard Biological Engineering Co Ltd
Original Assignee
Shenzhen Hansen Standard Biological Engineering Co Ltd
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 Shenzhen Hansen Standard Biological Engineering Co Ltd filed Critical Shenzhen Hansen Standard Biological Engineering Co Ltd
Priority to CN201911414584.6A priority Critical patent/CN110882211A/en
Publication of CN110882211A publication Critical patent/CN110882211A/en
Pending legal-status Critical Current

Links

Images

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/21Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/216Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acids having aromatic rings, e.g. benactizyne, clofibrate
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/32Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/0012Galenical forms characterised by the site of application
    • A61K9/0034Urogenital system, e.g. vagina, uterus, cervix, penis, scrotum, urethra, bladder; Personal lubricants
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/06Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00Drugs for genital or sexual disorders; Contraceptives
    • A61P15/02Drugs for genital or sexual disorders; Contraceptives for disorders of the vagina
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/02Local antiseptics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04Antibacterial agents

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Communicable Diseases (AREA)
  • Gynecology & Obstetrics (AREA)
  • Reproductive Health (AREA)
  • Oncology (AREA)
  • Engineering & Computer Science (AREA)
  • Endocrinology (AREA)
  • Urology & Nephrology (AREA)
  • Inorganic Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Emergency Medicine (AREA)
  • Cosmetics (AREA)
  • Medicinal Preparation (AREA)
  • Agricultural Chemicals And Associated Chemicals (AREA)

Abstract

The invention discloses a hydroxyphenyl ester gel, and relates to the technical field of medicines. The hydroxyphenyl ester gel contains carbomer, which is beneficial to uniformly dispersing hydroxyphenyl ester bacteriostatic agent in the gel and promoting the bacteriostatic agent to better exert the drug effect; citric acid helps to promote the dissolution and dispersion of carbomer to form a uniform suspension; the functional oligosaccharide component has proliferation and growth promoting effects on lactobacillus and epithelial cells, and helps to accelerate recovery of damaged parts; the acidity regulator can adjust the pH value of the gel, ensure that the parabens gel is not rejected and irritated, and improve the use experience of patients; the technical scheme can play a role in synergy under the combined action of all components, so that the sterilizing substance in the hydroxyphenyl ester gel is stable, has good antibacterial and bactericidal effects and biocompatibility, is free of irritation and better in use experience, and can better play a role in bacteriostasis and sterilization.

Description

Hydroxyphenyl ester gel and preparation method thereof
Technical Field
The invention relates to the technical field of medicines, and in particular relates to a hydroxyphenyl ester gel and a preparation method thereof.
Background
Gels refers to thick liquid or semisolid preparations of the solution, suspension or emulsion type made of a drug and excipients capable of forming a gel. Gels are typically topically applied to the skin and body cavities (e.g., nasal, vaginal, and rectal). The hydrogel matrix gel is mainly applied clinically.
The common aqueous gel matrix is carbomer, which is a high molecular polymer of acrylic acid crosslinked with allyl sucrose or allyl pentaerythritol. The gel containing carbomer has the advantages of excellent adhesiveness, water retention, slow release and the like, can effectively combine bacteriostatic components, and jointly play an ideal treatment role in focal parts, particularly in female genital tract infectious diseases.
The hydroxyphenyl ester substance is used as a common bacteriostatic component in the gel, has various forms, mainly comprises methyl ester, ethyl ester, propyl ester, butyl ester and amyl ester, has strong inhibiting effect on the proliferation and growth of various microorganisms, particularly yeast and mould, and is commonly used in the fields of daily chemical industry, medicine and food industry. The bacteriostatic agent selected in patent CN102861116B is methyl hydroxybenzoate or ethyl hydroxybenzoate, which has higher solubility but weaker bacteriostatic ability than propyl hydroxybenzoate, butyl hydroxybenzoate or amyl hydroxybenzoate. Patent CN108743575A shows that oxybenzone butyl ester does not affect the growth of human cells, is not easy to generate drug resistance, and has strong capacity of resisting Candida albicans infection.
However, the existing gel for treating the female genital tract infectious diseases is easy to pollute clothes due to low viscosity, is easy to dehydrate to cause poor use experience of patients, and is easy to cause disease recurrence due to low bacteriostatic effect.
Disclosure of Invention
The invention aims to solve the technical problem of the prior art and provides a hydroxyphenyl ester gel with good antibacterial effect, no irritation and stable property and a preparation method thereof.
In order to solve the above problems, the present invention proposes the following technical solutions:
in a first aspect, an embodiment of the present invention provides a hydroxyphenyl ester gel, which comprises the following components, by mass:
1-6% carbomer;
1-5% functional oligosaccharide;
0.6 to 1.1 percent of citric acid;
1.2 to 2.3 percent of acidity regulator;
7 to 16 percent of humectant;
0.06% -0.25% of hydroxyphenyl bacteriostat;
the balance being purified water.
Preferably, the functional oligosaccharide is at least one of isomaltooligosaccharide, fructooligosaccharide, galactooligosaccharide, raffinose, stachyose and xylooligosaccharide.
Preferably, the acidity regulator is triethanolamine or sodium hydroxide.
Preferably, the humectant is 1, 3-propanediol and/or glycerol.
Preferably, the hydroxyphenyl bacteriostatic agent is propyl hydroxyphenyl, butyl hydroxyphenyl or amyl hydroxyphenyl.
Preferably, the pH of the hydroxyphenyl ester gel is 3.8 to 4.5.
In a second aspect, an embodiment of the present invention provides a method for preparing the hydroxyphenyl ester gel, which includes the following steps:
s1, dissolving the citric acid in 2/3-4/5 volumes of purified water according to a proportion, adding the carbomer after completely dissolving, fully mixing, and swelling for more than 4 hours to obtain a carbomer matrix;
s2, fully dissolving the functional oligosaccharide in 1/6-1/5 volume of purified water to obtain a functional oligosaccharide solution;
s3, dissolving the hydroxyphenyl ester bacteriostatic agent in the acidity regulator, adding the humectant, and fully and uniformly mixing to obtain a bacteriostatic agent solution;
and S4, mixing the carbomer matrix, the functional oligosaccharide solution, the bacteriostatic agent solution and the residual volume of purified water to obtain a mixture, and performing vacuum degassing for more than 30min after the mixture is completely and uniformly dispersed to form transparent or semitransparent homogeneous gel without flocculent foreign matters, thus obtaining the hydroxyphenyl ester gel.
Compared with the prior art, the invention can achieve the following technical effects:
according to the hydroxyphenyl ester gel provided by the invention, carbomer is added, so that the gel has a rheological regulation effect, the hydroxyphenyl ester bacteriostatic agent can be uniformly dispersed in the gel, and the drug effect can be better exerted; citric acid helps to promote the dissolution and dispersion of carbomer to form a uniform suspension; the functional oligosaccharide component has the functions of promoting the proliferation and the growth of the lactobacillus and epithelial cells, and the concentration range of the functional oligosaccharide selected by the invention is the optimal concentration for the growth of the lactobacillus, which is beneficial to the proliferation and the growth of the lactobacillus by using the functional oligosaccharide as a carbon source; the acidity regulator is used for regulating the pH value of the gel, so that the parabens gel at the use part is not rejected and stimulated, and the use experience of a patient is improved; the technical scheme has the advantages that the components can play a role in synergy under the combined action, so that the hydroxyphenyl ester gel has long-term stable performance, has good antibacterial and bactericidal effects and biocompatibility, and has excellent use experience for patients.
The preparation method of the hydroxyphenyl ester gel provided by the invention comprises the following steps:
(1) the hydroxyphenyl ester bacteriostatic agent is dissolved by the acidity regulator to form a homogeneous solution, and then the homogeneous solution is stirred and mixed with the carbomer gel matrix, so that the hydroxyphenyl ester bacteriostatic agent can be uniformly dispersed in the gel matrix, and the bacteriostatic effect of the hydroxyphenyl ester bacteriostatic agent can be exerted to the maximum extent.
(2) The hydroxyphenyl ester bacteriostatic agent is neutral, non-irritant, almost non-toxic, has the strongest bacteriostatic action at the pH of 3-6, has the most stable property, ensures that the final pH value of the gel is 3.8-4.5 by using the acid-base regulator, has the pH value range consistent with the normal pH value range of the female genital tract, and can ensure the bacteriostatic effect of the hydroxyphenyl ester bacteriostatic agent and not destroy the microecology of the female vagina when being used for treating the female genital tract infection.
(3) The hydroxyphenyl ester gel prepared by the preparation method of hydroxyphenyl ester gel provided by the invention has stable chemical property, and can be stored for two years or even longer under the condition of normal temperature; the biocompatibility evaluation is good, the cytotoxicity is graded as 1 grade, sensitization is not caused, and the vaginal mucosa is not stimulated.
Drawings
In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings needed to be used in the description of the embodiments are briefly introduced below, and it is obvious that the drawings in the following description are some embodiments of the present invention, and it is obvious for those skilled in the art to obtain other drawings based on these drawings without creative efforts.
Fig. 1 is a graph showing the bacteriostatic results of the paraben gel containing butylparaben or propylparaben on bacteria according to the embodiment of the present invention;
FIG. 2 is a diagram showing the bacteriostatic results of different concentrations of butylparaben on Candida albicans in the paraben gel of the present invention;
fig. 3 is a graph showing the bacteriostatic results of staphylococcus aureus caused by different concentrations of butylparaben in the paraben gel provided by the embodiment of the invention;
fig. 4 is a graph showing the bacteriostatic results of the oxybenzone butyl esters gel containing different concentrations on escherichia coli.
Detailed Description
The technical solutions in the embodiments will be described clearly and completely with reference to the accompanying drawings in the embodiments of the present invention, wherein like reference numerals represent like elements in the drawings. It is apparent that the embodiments to be described below are only a part of the embodiments of the present invention, and not all of them. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
The embodiment of the invention provides a hydroxyphenyl ester gel which comprises the following components in percentage by mass:
1-6% carbomer;
1-5% functional oligosaccharide;
0.6 to 1.1 percent of citric acid;
1.2 to 2.3 percent of acidity regulator;
7 to 16 percent of humectant;
0.06% -0.25% of hydroxyphenyl bacteriostat;
the balance being purified water.
In one embodiment, the carbomer is carbomer 940.
In one embodiment, the carbomer is carbomer 980.
The preparation method has the advantages that the rheological control effect of the carbomer is utilized, the carbomer is added into the hydroxyphenyl ester gel, so that the hydroxyphenyl ester bacteriostatic agent is favorably and uniformly dispersed in the gel, and the drug effect of the hydroxyphenyl ester bacteriostatic agent on the using part is better exerted.
In other embodiments, the functional oligosaccharide is at least one of isomaltooligosaccharide, fructooligosaccharide, galactooligosaccharide, raffinose, stachyose, and xylooligosaccharide.
The functional oligosaccharide used in the embodiment has the functions of promoting proliferation and growth of dominant bacteria in the vagina, such as lactobacillus and epithelial cells, is beneficial to the proliferation and growth of the lactobacillus by using the functional oligosaccharide as a carbon source, accelerates the restoration of flora and the repair of inflammation at the use part, and improves the treatment effect.
For example, in one embodiment, the functional oligosaccharide is a mixture of fructooligosaccharides and galactooligosaccharides.
In one embodiment, the functional oligosaccharide is stachyose.
In one embodiment, the functional oligosaccharide is xylo-oligosaccharide.
In one embodiment, the acidity regulator is triethanolamine.
In one embodiment, the acidity regulator is a 10% sodium hydroxide solution.
The acidity regulator is helpful for regulating the pH value of the hydroxyphenyl ester gel, so that the pH value is the same as or close to that of the using part, and the hydroxyphenyl ester gel has better biocompatibility. For example, the normal pH of the female genital tract is in the range of 3.8 to 4.5, and the pH of the hydroxyphenyl gel provided in this embodiment is in the range of 3.8 to 4.5. The pH value range is consistent with the normal pH value range of female genital tracts, and the microecology of female vaginas is not damaged.
In one embodiment, the humectant is 1, 3-propanediol.
In one embodiment, the paraben bacteriostatic agent is propyl paraben, butyl paraben or amyl paraben.
In one embodiment, the hydroxyphenyl bacteriostatic agent is hydroxyphenyl amyl ester.
The embodiment of the invention also provides a preparation method of the hydroxyphenyl ester gel, which comprises the following steps:
s1, dissolving the citric acid in 2/3 volume of purified water according to a proportion, adding the carbomer after completely dissolving, fully mixing, and swelling for more than 4 hours to obtain a carbomer matrix;
s2, fully dissolving the functional oligosaccharide in 1/5 volume of purified water to obtain a functional oligosaccharide solution;
s3, dissolving the hydroxyphenyl ester bacteriostatic agent in the acidity regulator, adding the humectant, and fully and uniformly mixing to obtain a bacteriostatic agent solution;
and S4, mixing the carbomer matrix, the functional oligosaccharide solution, the bacteriostatic agent solution and the residual volume of purified water to obtain a mixture, and performing vacuum degassing for more than 30min after the mixture is completely and uniformly dispersed to form transparent or semitransparent homogeneous gel without flocculent foreign matters, thus obtaining the hydroxyphenyl ester gel.
Example 1
The embodiment of the invention provides a hydroxyphenyl ester gel which comprises the following raw materials in percentage by mass:
carbomer 940, 2%;
isomaltose hypgather, 2%;
1% of citric acid;
triethanolamine, 2%;
10% of glycerol;
0.25% of propyl hydroxybenzoate;
the balance being purified water.
The embodiment of the invention also provides a preparation method of the hydroxyphenyl ester gel, which comprises the following steps:
1. weighing/weighing
(1) Weighing of purified water
Three portions of purified water, namely 596g of purified water, 146g of purified water and 87g of purified water are respectively put into 3 clean containers for standby.
(2) Weighing of raw materials
Weighing 20.0g of carbomer, 20.0g of isomaltooligosaccharide, 10.0g of citric acid, 20.0g of triethanolamine, 100.0g of glycerol and 2.5g of butyl hydroxybenzoate, and respectively filling the weighed materials into 6 clean containers for later use.
2. Preparation of component A
Slowly pouring citric acid into the first part of purified water, adding carbomer after complete dissolution, adding carbomer for multiple times, stirring at room temperature until complete dissolution, standing at room temperature for swelling for more than 4h after complete dissolution to obtain carbomer gel matrix, and recording as component A for later use. The process avoids caking.
3. Preparation of component B
And adding the isomaltooligosaccharide into the second part of purified water, stirring at room temperature, and completely dissolving to obtain an isomaltooligosaccharide solution, which is marked as component B for later use.
4. Preparation of component C
Slowly pouring the propyl hydroxybenzoate into triethanolamine, dissolving completely, adding glycerol, and mixing to obtain propyl hydroxybenzoate antibacterial solution, as component C.
5. Stirring the mixture
(1) Pouring the component A and the component B into a stirring tank in sequence, and setting the revolution speed of the stirring tank to be 35 revolutions per minute, the rotation speed to be 35 revolutions per minute and the stirring time to be 15 minutes to fully and uniformly mix the components A and B;
(2) adding the component C, washing residual liquid in the container with third part of purified water, pouring all the washing liquid into the stirring tank, closing the upper cover of the stirring tank, setting the stirring time to be 45 minutes, and continuing stirring to completely mix the components.
6. Degassing of gases
And opening a vacuum pump of the stirring tank and continuously stirring, degassing for 1h, closing the vacuum pump and stopping stirring after degassing is finished, and opening an upper cover of the stirring tank to obtain transparent or semitransparent homogeneous gel, namely the hydroxyphenyl gel.
Example 2
The embodiment of the invention provides a hydroxyphenyl ester gel which comprises the following raw materials in percentage by mass: carbomer 980, 4%
5 percent of raffinose
Citric acid, 0.8%
Triethanolamine, 1.6%
1, 3-propanediol, 8%
Propyl hydroxybenzoate, 0.15%
The balance being purified water.
The preparation method is the same as example 1.
Example 3
The embodiment of the invention provides a hydroxyphenyl ester gel which comprises the following raw materials in percentage by mass: carbomer 940, 1%
1 percent of fructo-oligosaccharide
Citric acid, 0.7%
Triethanolamine, 1.5%
Glycerol, 14%
Hydroxyphenyl amyl ester, 0.08%
The balance being purified water.
The preparation method is the same as example 1.
Example 4
The embodiment of the invention provides a hydroxyphenyl ester gel which comprises the following raw materials in percentage by mass:
carbomer 980, 1%
Xylo-oligosaccharide, 2%
Citric acid, 0.9%
Triethanolamine, 1.2%
Glycerol, 16%
0.2 percent of butyl hydroxybenzoate
The balance being purified water.
The preparation method is the same as example 1.
Example 5
The embodiment of the invention provides a hydroxyphenyl ester gel which comprises the following raw materials in percentage by mass:
carbomer 940, 2%
Xylo-oligosaccharide, 2%
Citric acid, 0.9%
Triethanolamine, 1.7%
Glycerol, 13%
Propyl hydroxybenzoate, 0.1%
The balance being purified water.
The preparation method is the same as example 1.
Example 6
The embodiment of the invention provides a hydroxyphenyl ester gel, which is different from the embodiment 5 in that the hydroxyphenyl ester bacteriostatic agent is butyl hydroxybenzoate.
Sterilization Effect verification 1
1. Criterion for judging bactericidal effect
The sterilization experiment evaluation standard is that the sterilization rate is more than or equal to 90 percent, and the sterilization is judged to have the sterilization effect; actually, in order to ensure the effectiveness of the hydroxyphenyl ester gel, the judgment standard of the bactericidal effect is shown in table 1:
TABLE 1 Sterilization Effect judgment Standard Table
Figure BDA0002350862210000081
2. Test materials and methods
(1) The formula of the Sabouraud's agar culture medium is as follows:
10g of peptone, 40g of glucose, 15g of agar powder, 50-100 mg of chloramphenicol and 500mL of purified water; is used for enrichment culture of candida albicans.
(2) General broth agar medium formula:
5g of peptone, 1.5g of beef extract powder, 2.5g of sodium chloride, 7.5g of agar powder and 500mL of purified water; is used for enrichment culture of staphylococcus aureus and escherichia coli.
(3) Preparation of a culture medium:
a. weighing the raw materials according to the culture medium formulas in the step (1) and the step (2) for later use;
b. weighing a proper amount of purified water in a clean beaker, pouring the purified water into the clean beaker, continuously stirring the mixture on a magnetic stirrer until the mixture is completely dissolved, adding the purified water to a constant volume of 500mL, subpackaging the mixture in two conical flasks, and autoclaving the mixture together with a clean culture dish for pouring a flat plate at 121 ℃ for 15-30 min.
c. After the sterilization is finished, transferring the culture medium and the culture dishes into a super clean bench, opening a ventilation system, subpackaging proper culture mediums in each culture dish when the temperature of the culture medium is reduced to 45-55 ℃, and cooling for later use.
(4) Preparation of physiological saline:
weighing 9g of sodium chloride in a beaker, dissolving a proper amount of purified water, adding purified water to a constant volume of 1000mL, and carrying out autoclaving at 121 ℃ for 15-30 min for later use to obtain a bacterial liquid diluent.
(5) Preparation of test bacterial solution
Taking out the original strain liquid, activating overnight, adjusting the OD600nm value of the strain liquid to 1.0 by Candida albicans, wherein the strain concentration is about 3 × 107cfu/mL, diluting by 60 times with physiological saline to prepare a bacterial suspension for later use; the adjusted staphylococcus aureus/escherichia coli bacterial liquid OD600nm value was 1.0, and the bacterial concentration was about 3 × 10 at this time8cfu/mL, and preparing a bacterial suspension for later use after being diluted by 30 times by using physiological saline.
3. Test grouping
Groups were made according to the different contents of the plates, and the specific contents of each group are shown in Table 2. The blank group is a culture medium, the negative group is a culture medium containing normal saline or 4% citric acid, the positive group is a culture medium containing bacterial suspension and normal saline or 4% citric acid, and the experimental group is a culture medium containing bacterial suspension and the hydroxyphenyl gel provided by the invention.
It should be noted that, in table 2, the 0.1% of the hydroxypropyl paraben gel in experimental groups 1.1-1.3 is the paraben gel provided in example 5 of the present invention; 0.1 percent of oxybenzene butyl ester gel in the experimental group 2.1-2.3 is the oxybenzene ester gel provided by the embodiment 6 of the invention;
TABLE 2 is the bacteriostatic test table of butyl and propyl hydroxybenzene esters
Figure BDA0002350862210000101
4. Test procedure
(1) The hydroxyphenyl ester gel agents used in the experimental groups 1.1-1.2 and 2.1-2.2 are liquefied by 3 times of citric acid, the hydroxyphenyl ester gel agents used in the experimental groups 1.3 and 2.3 are added with normal saline according to the volume ratio of 2:1, 540 mu L of the hydroxyphenyl ester gel agents are respectively mixed with 60 mu L of test bacterial liquid for 30min, and corresponding gel bacterial suspension is obtained.
(2) 200 mu L of gel bacterial suspension is respectively taken according to the grouping conditions in the table 2 and is dripped on the surface of a culture medium flat plate, the gel bacterial suspension is evenly coated by a coating rod, 2 parallel groups are arranged in each test group, the group and the date are marked, and the gel bacterial suspension is cultured for more than 16h in a constant-temperature bacteria incubator at 37 ℃.
(3) The growth of Candida albicans, Staphylococcus aureus and Escherichia coli in each group was observed, counted and analyzed.
5. Statistical and analysis of test results
(1) The statistical method comprises the following steps:
the test results were calculated according to the following formula:
Figure BDA0002350862210000111
Figure BDA0002350862210000112
Figure BDA0002350862210000113
(2) the test results, as shown in fig. 1 and table 3:
TABLE 3 test results
Figure BDA0002350862210000114
Figure BDA0002350862210000121
From the results shown in fig. 1 and table 3, it can be seen that when the amount of the paraben bacteriostatic agent is 0.1%, in combination with other components, 0.1% of the paraben and 0.1% of the paraben have very significant inhibitory effects on the growth of candida albicans, staphylococcus aureus and escherichia coli, and the bacteriostatic effect is substantially 100%. The propyl hydroxybenzoate and butyl hydroxybenzoate in the gel have ideal bacteriostatic effect, so both can be the preferred paraben bacteriostatic agent.
Sterilization effect verification 2
1. The judgment criteria of the bactericidal effect are shown in Table 1.
2. Test materials and methods see Sterilization verification 1
3. Test grouping
The minimum inhibitory concentration of the hydroxyphenyl ester gel provided by the embodiment of the invention is respectively tested, butyl hydroxybenzoate is used as a hydroxyphenyl ester bacteriostatic agent, the inhibitory effect of different concentrations of butyl hydroxybenzoate is tested, and the content of the rest components is shown in the embodiment 5. Groups were made according to the different contents of the plates, and the specific contents of each group are shown in tables 4-6.
3.1. Minimum inhibitory concentration test group of butyl hydroxybenzoate to candida albicans
TABLE 4 shows the bacteriostasis test table of hydroxyl-benzene butyl ester with different concentrations to candida albicans
Figure BDA0002350862210000122
Figure BDA0002350862210000131
3.2. Minimum inhibitory concentration test group of butyl hydroxybenzoate to staphylococcus aureus
TABLE 5 bacteriostatic test table for Staphylococcus aureus with butyl hydroxybenzoate of different concentrations
Figure BDA0002350862210000132
3.3. Minimum inhibitory concentration test group of butyl hydroxybenzoate to escherichia coli
TABLE 6 is the bacteriostatic test table of oxybutyl ester with different concentrations for Escherichia coli
Figure BDA0002350862210000133
Figure BDA0002350862210000141
4. Test procedure
(1) The hydroxyphenyl ester gel provided by the experimental groups 3.1-3.5 and 4.1-4.3 is liquefied by using citric acid with the volume being 3 times that of the hydroxyphenyl ester gel provided by the experimental groups 5.1-5.3, physiological saline is added into the hydroxyphenyl ester gel provided by the experimental groups 5.1-5.3 according to the volume ratio of 2:1, 540 mu L of the hydroxyphenyl ester gel is mixed with 60 mu L of test bacterium liquid respectively, and the corresponding gel bacterium suspension is prepared.
(2) And (3) dropwise adding 200 mu L of gel bacterial suspension to the surface of a culture medium flat plate, uniformly coating the gel bacterial suspension by using a coating rod, setting 2 parallel groups in each test group, marking the groups and dates, and culturing for more than 16h in a constant-temperature bacteria incubator at 37 ℃.
(3) And observing, counting and analyzing the growth conditions of candida albicans, staphylococcus aureus and escherichia coli.
5. Statistical and analysis of test results
(1) See bactericidal Effect verification 1 for statistical methods
(2) The test results are shown in FIGS. 2 to 4 and tables 7 to 9:
TABLE 7 analysis of minimum inhibitory concentration of butylparaben against Candida albicans
Figure BDA0002350862210000142
Figure BDA0002350862210000151
TABLE 8 minimum inhibitory concentration analysis of oxybenzoyl butyl ester on Staphylococcus aureus
Test group Average growth rate
Blank group 2 0
Negative group 2 0
Negative group 4 0
Positive group 2 100%
Positive group 5 100%
Experimental group 4.1 0
Experimental group 4.2 0
Experimental group 4.3 0
TABLE 9 minimum inhibitory concentration analysis of oxybenzoyl butyl ester on E.coli
Test group Average growth rate
Blank group 2 0
Negative group 2 0
Negative group 4 0
Positive group 3 100%
Positive group 6 100%
Experimental group 5.1 0
Experimental group 5.2 0
Experimental group 5.3 0
As can be seen from FIGS. 2 to 4 and tables 7 to 9: under the condition that other conditions are completely consistent, compared with a positive group, the hydroxyphenyl ester gel provided by the embodiment of the invention has a dose-dependent inhibition effect on the growth of candida albicans, namely, the higher the concentration of butyl hydroxybenzoate is, the stronger the inhibition capacity on the proliferation and growth of colonies is, but when the concentration of butyl hydroxybenzoate is more than 0.06%, the hydroxyphenyl ester gel can completely inhibit the proliferation and growth of candida albicans, and the higher dose has no difference in bacteriostasis effect, but rather leads to the increase of production cost. And staphylococcus aureus and escherichia coli are more sensitive to butylparaben, so that the concentration range of butylparaben is reduced to 0.04-0.08% in the minimum inhibitory concentration test of butylparaben to staphylococcus aureus/escherichia coli. It was found that a gel of the paraben type containing 0.04% of butylparaben was sufficient to completely inhibit the proliferation of Staphylococcus aureus and Escherichia coli.
In conclusion, the minimum inhibitory concentration of the hydroxyphenyl bacteriostatic agent in the hydroxyphenyl gel provided by the invention is about 0.06%, so that the proliferation and growth of candida albicans, staphylococcus aureus and escherichia coli can be completely and effectively inhibited, and the broad-spectrum antibacterial property is strong.
In the above embodiments, the descriptions of the respective embodiments have respective emphasis, and for parts that are not described in detail in a certain embodiment, reference may be made to related descriptions of other embodiments.
While the invention has been described with reference to specific embodiments thereof, it will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the spirit and scope of the invention as defined by the appended claims. Therefore, the protection scope of the present invention shall be subject to the protection scope of the claims.

Claims (7)

1. The hydroxyphenyl gel is characterized by comprising the following components in percentage by mass:
1-6% carbomer;
1-5% functional oligosaccharide;
0.6 to 1.1 percent of citric acid;
1.2 to 2.3 percent of acidity regulator;
7 to 16 percent of humectant;
0.06% -0.25% of hydroxyphenyl bacteriostat;
the balance being purified water.
2. The hydroxyphenyl gel of claim 1, wherein the functional oligosaccharide is at least one of isomaltooligosaccharide, fructooligosaccharide, galactooligosaccharide, raffinose, stachyose and xylooligosaccharide.
3. The paraben gel of claim 1, wherein said acidity regulator is triethanolamine or sodium hydroxide.
4. The hydroxyphenyl gel of claim 1 in which the humectant is 1, 3-propanediol and/or glycerin.
5. The paraben gel of claim 1 wherein said paraben bacteriostatic agent is propyl paraben, butyl paraben, or amyl paraben.
6. The hydroxyphenyl ester gel of claim 1, wherein the hydroxyphenyl ester gel has a pH of from 3.8 to 4.5.
7. A method for preparing the hydroxyphenyl gel of any one of claims 1 to 6, which comprises the steps of:
s1, dissolving the citric acid in 2/3-4/5 volumes of purified water according to a proportion, adding the carbomer after completely dissolving, fully mixing, and swelling for more than 4 hours to obtain a carbomer matrix;
s2, fully dissolving the functional oligosaccharide in 1/6-1/5 volume of purified water to obtain a functional oligosaccharide solution;
s3, dissolving the hydroxyphenyl ester bacteriostatic agent in the acidity regulator, adding the humectant, and fully and uniformly mixing to obtain a bacteriostatic agent solution;
and S4, mixing the carbomer matrix, the functional oligosaccharide solution, the bacteriostatic agent solution and the residual volume of purified water to obtain a mixture, and performing vacuum degassing for more than 30min after the mixture is completely and uniformly dispersed to form transparent or semitransparent homogeneous gel without flocculent foreign matters, thus obtaining the hydroxyphenyl ester gel.
CN201911414584.6A 2019-12-31 2019-12-31 Hydroxyphenyl ester gel and preparation method thereof Pending CN110882211A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201911414584.6A CN110882211A (en) 2019-12-31 2019-12-31 Hydroxyphenyl ester gel and preparation method thereof

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201911414584.6A CN110882211A (en) 2019-12-31 2019-12-31 Hydroxyphenyl ester gel and preparation method thereof

Publications (1)

Publication Number Publication Date
CN110882211A true CN110882211A (en) 2020-03-17

Family

ID=69753487

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201911414584.6A Pending CN110882211A (en) 2019-12-31 2019-12-31 Hydroxyphenyl ester gel and preparation method thereof

Country Status (1)

Country Link
CN (1) CN110882211A (en)

Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101773516A (en) * 2009-11-26 2010-07-14 上海华拓医药科技发展股份有限公司 Acidic buffer gel preparation for vaginas and preparation method and application thereof
WO2012031186A1 (en) * 2010-09-03 2012-03-08 Wisconsin Pharmacal Company, Llc. Prebiotic suppositories
CN103313700A (en) * 2010-10-21 2013-09-18 高德美国际公司 Topical gel composition
WO2015018134A1 (en) * 2013-08-09 2015-02-12 南京泛成生物化工有限公司 Exfoliating gel and preparation method thereof
CN104382998A (en) * 2014-11-25 2015-03-04 成都顺发消洗科技有限公司 Carbomer gel and preparation method thereof
CN108452293A (en) * 2018-04-12 2018-08-28 广西达庆生物科技有限公司 A kind of gynaecology's gel and preparation method thereof
CN110575431A (en) * 2019-08-28 2019-12-17 南京天朗制药有限公司 Vaginal acid-base buffer gel and preparation method thereof
CN112773860A (en) * 2021-01-18 2021-05-11 澳邦制药(横琴)有限公司 Wanying ointment and preparation method thereof

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101773516A (en) * 2009-11-26 2010-07-14 上海华拓医药科技发展股份有限公司 Acidic buffer gel preparation for vaginas and preparation method and application thereof
WO2012031186A1 (en) * 2010-09-03 2012-03-08 Wisconsin Pharmacal Company, Llc. Prebiotic suppositories
CN103313700A (en) * 2010-10-21 2013-09-18 高德美国际公司 Topical gel composition
WO2015018134A1 (en) * 2013-08-09 2015-02-12 南京泛成生物化工有限公司 Exfoliating gel and preparation method thereof
CN104382998A (en) * 2014-11-25 2015-03-04 成都顺发消洗科技有限公司 Carbomer gel and preparation method thereof
CN108452293A (en) * 2018-04-12 2018-08-28 广西达庆生物科技有限公司 A kind of gynaecology's gel and preparation method thereof
CN110575431A (en) * 2019-08-28 2019-12-17 南京天朗制药有限公司 Vaginal acid-base buffer gel and preparation method thereof
CN112773860A (en) * 2021-01-18 2021-05-11 澳邦制药(横琴)有限公司 Wanying ointment and preparation method thereof

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
鄢海燕等: "《高职高专"十三五"规划教材 药剂学 第2版》", 31 January 2018, 江苏科学技术出版社 *

Similar Documents

Publication Publication Date Title
US8586549B2 (en) Composition and method for modulating and maintaining vaginal bacterial flora and vaginal acidity
CN100457084C (en) Nanometer silver type external use antibiotic gel for female external use and its prepn. method
CN112190542B (en) Aqueous in-situ gel ophthalmic preparation for treating xerophthalmia
CN113730433B (en) Gynecological gel for treating colpitis and preparation method and application thereof
CN105919926A (en) Carbomer cervical gel and preparation method thereof
CN114652748A (en) Preparation method and application of medical gynecological lotion containing stem cell bacteriostatic factors
CN111973801B (en) Hydrogel for anti-inflammatory repair and preparation method thereof
CN103655601B (en) A kind of composition for Intravesical instillation
CN111991417A (en) Hypochlorous acid gel with physiological responsiveness and application thereof in skin wound surface
CN109512851B (en) Preparation method of medical antibacterial midwifery gel
CN110882211A (en) Hydroxyphenyl ester gel and preparation method thereof
CA3061270C (en) Bladder instillation composition containing chondroitin sulfate (20 mg/ml), hyaluronic acid (16 mg/ml), and a phosphate buffer (ph 6.1 to 7.9) with increased storage stability for treating cystitis
CN109078069B (en) Vaginal mucosa antibacterial gel and preparation method thereof
CN113209202A (en) Bacteriostatic gynecological lotion and preparation method thereof
RU2354392C1 (en) Remedy for treating bacterial vaginosis and method of bacterial vaginosis treatment
CN108066278B (en) Gynecological gel containing chitosan oligosaccharide and preparation method thereof
WO2017193509A1 (en) Bionic gynecological lotion and preparation method therefor
CN103520091A (en) Acidic buffer temperature-sensitive gel preparation for vagina as well as preparation method and application thereof
CN109745300B (en) Physical contraceptive gel film-forming agent without spermicide
CN111329846A (en) Vaginal sterilization adhesive film and preparation method thereof
RU2286800C1 (en) Antibacterial filler for female absorbent articles, method for production and uses thereof
CN111759852A (en) Pharmaceutical composition for vagina, pharmaceutical preparation, preparation method and application thereof
CN111617099A (en) Nonreactive high-cell affinity colitis restoration agent and application method thereof
CN111888430B (en) Composite antibacterial gel and preparation method and application thereof
CN114533679B (en) Sulfachlorpyridazine sustained-release nano colloidal particle 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
RJ01 Rejection of invention patent application after publication

Application publication date: 20200317

RJ01 Rejection of invention patent application after publication