CN108853004A - A method of preparing metronidazole vagina gel - Google Patents
A method of preparing metronidazole vagina gel Download PDFInfo
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- CN108853004A CN108853004A CN201810821519.4A CN201810821519A CN108853004A CN 108853004 A CN108853004 A CN 108853004A CN 201810821519 A CN201810821519 A CN 201810821519A CN 108853004 A CN108853004 A CN 108853004A
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
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- 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
- A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/02—Drugs for genital or sexual disorders; Contraceptives for disorders of the vagina
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
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Abstract
The present invention relates to a kind of methods for preparing metronidazole vagina gel, and this method comprises the following steps：(1) natrium adetate is mixed with water, adds CARBOPOL 974P, sufficiently carried out vacuum emulsifying after swelling, obtain gel-type vehicle；(2) pH value for adjusting the gel-type vehicle is 4.0~4.5, obtains Blank gel；(3) by methyl p-hydroxybenzoate and propylparaben with mass ratio 2~6:1 mixing is added in propylene glycol, obtains propylene glycol solution；The propylene glycol solution is mixed with water, be added metronidazole sufficiently dissolve, then with the Blank gel be sufficiently mixed to get.Scheme provided by the invention is optimized to metronidazole vagina Process for preparing hydrogels, raw material order of addition and hybrid mode is prepared, especially the common carbomer940 of the prior art is replaced with CARBOPOL 974P, pharmaceutical effectiveness performance does not subtract after ensuring to replace auxiliary material, and safety is higher.
Description
Technical field
The present invention relates to gynecopathy therapeutic and related drugs field, and in particular to a kind of metronidazole vagina gel for preparing
Method.
Background technique
Bacterial vaginitis (BV) is a kind of mixed infection by vagina Gartner bacterium and some anaerobic bacterias, leads to intravaginal
Microecological balance imbalance, caused vaginal fluid increases, and leukorrhea has fish bad smell and the scorching hot syndrome of pruritus vulvue.It can divide
For haemophilus property vaginitis, Corynebacterium vaginitis, anaerobic bacteria vaginosis inflammation, Gardnerella Vaginalis Vaginitis etc..
The most frequently used drug of the metronidazole as bacterial vaginosis BV, clinical acceptance level are very high；《U.S.'s disease control in 2010
Vaginitis treatment guide in center processed》It is drafted with Chinese Medical Association《Bacterial vaginosis BV diagnosis and treatment guide (draft)》Preferred option is equal
For metronidazole；But oral or ejection preparation side effect is big, is easy to produce anaphylactic shock and the nervous system disease, patient tolerability
Difference.The preparation that external application is made can then make drug mainly in the local action of medication, and pharmacokinetic study shows solidifying using vagina
Patient's metronidazole serum-concentration of glue preparation is only the 2% of oral preparation, Small side effects, and curative effect is better than oral preparation, Huan Zhenai
It is greatly improved by property.
However, existing metronidazole external preparation is easy to happen microbial contamination, and safety in storage and use process
Property is not ideal enough.
Summary of the invention
It is an object of the invention to overcome the deficiencies of existing technologies, a kind of method for preparing metronidazole vagina gel is provided.
Scheme provided by the invention is excellent to metronidazole vagina Process for preparing hydrogels, raw material order of addition and hybrid mode progress is prepared
Change, especially replace the common carbomer940 of the prior art with CARBOPOL 974P, it is ensured that pharmaceutical effectiveness performance after replacement auxiliary material
Do not subtract, and safety is higher." P " in CARBOPOL 974P or carbomer940 of the present invention refers to that the auxiliary material is orally available
Auxiliary material.
Specifically, method provided by the invention includes the following steps：
(1) natrium adetate is mixed with water, adds CARBOPOL 974P, sufficiently carry out vacuum emulsifying after swelling,
Obtain gel-type vehicle；
(2) pH value for adjusting the gel-type vehicle is 4.0~4.5, obtains Blank gel；
(3) by methyl p-hydroxybenzoate and propylparaben with mass ratio 2~6:Propylene glycol is added in 1 mixing
In, obtain propylene glycol solution；The propylene glycol solution is mixed with water, be added metronidazole sufficiently dissolve, then with the Blank gel
Be sufficiently mixed to get.
The present invention replaces the common carbomer940 of the prior art with CARBOPOL 974P, and is sufficiently swollen, due to
Carbomer940 is that the technique of benzene as the solvent used produces, and is easy output dissolvent residual, benzene toxicity is carcinogenic greatly, and 974p is then
It is to be produced with non-toluene solvent technique；Formula provided by the invention not only more meets the requirement of pharmacopeia and relevant regulations, Er Qietong
Cross the synergistic effect with other components, it can be ensured that in the case that gel transdermal absorbent properties and curative effect performance do not subtract, safety
Property is higher.
The pH value of the gel-type vehicle is adjusted in method needs provided by the invention.Specifically, the present invention selects
PH value is adjusted after obtaining gel-type vehicle, being preferably added to sodium hydroxide makes pH value reach 4.0~4.5, obtains Blank gel, can
When ensuring to stir containing each component and Blank gel homogeneous, optimal stable state is kept, so that it is guaranteed that final product is by long-term
Still there is good antibacterial effect and excellent Transdermal absorption performance after placement.
The present invention by largely practice discovery, by metronidazole, methyl p-hydroxybenzoate, propylparaben and
Propylene glycol shares, and the mass ratio of methyl hydroxybenzoate and propylparaben uses card in above-mentioned particular range
When wave nurse 974P, it can be ensured that in the case that gel transdermal absorbent properties and curative effect performance do not subtract, safety is higher.
In order to ensure each component sufficiently dissolves, especially ensuring that can be evenly dispersed when each component is mixed with gel-type vehicle,
When the present invention preferably mixes methyl p-hydroxybenzoate and propylparaben in addition propylene glycol, it is heated to 45~55
DEG C sufficiently dissolution.The present invention further preferably mixes the propylene glycol solution with 45~55 DEG C of water, be added after metronidazole 45~
It is dissolved at 55 DEG C.
On the basis of carrying out preferred to preparation process, it is excellent that the present invention further carries out specific aim to the dosage of each component
Change, so that it is guaranteed that products therefrom has good comprehensive performance.
As a preferred solution of the present invention, described method includes following steps：
(1) 1~5 part of natrium adetate is mixed with water, adds 80~120 parts of CARBOPOL 974Ps, is sufficiently swollen laggard
Row vacuum emulsifying, obtains gel-type vehicle；
(2) it is 4.0~4.5 that sodium hydroxide is added in the gel-type vehicle and adjusts pH value, obtains Blank gel；
(2) 2~6 parts of methyl p-hydroxybenzoates and 0.5~1.5 part of propylparaben are added 130~160 parts
In propylene glycol, propylene glycol solution is dissolved by heating to obtain；The propylene glycol solution is mixed with water, adds 35~40 parts of metronidazoles,
Sufficiently dissolve to obtain mixed solution；The mixed solution is mixed with the Blank gel, homogeneous stirring to get.
Further preferably the method includes following specific steps by the present invention：
(1) 2~3 parts of natrium adetates are mixed with water, adds 95~105 parts of CARBOPOL 974Ps, is sufficiently swollen laggard
Row vacuum emulsifying, obtains gel-type vehicle；
(2) it is 4.0~4.5 that sodium hydroxide is added in the gel-type vehicle and adjusts pH value, obtains Blank gel；
(3) 3.5~4.5 parts of methyl p-hydroxybenzoates and 0.5~1.5 part of propylparaben are added 140~
In 150 parts of propylene glycol, propylene glycol solution is dissolved by heating to obtain；The propylene glycol solution is mixed with water, adds 37~38 parts of first
Nitre azoles sufficiently dissolves to obtain mixed solution；The mixed solution is mixed with the Blank gel, homogeneous stirring to get.
Water is all used in above steps, the total amount of water used in preferably each step of the present invention is 1~10 part, more preferably each step
The total amount of rapid water used is 4~6 parts.
The metronidazole vagina gel that the present invention protects the method to be prepared simultaneously.
Method provided by the invention is to preparing metronidazole vagina Process for preparing hydrogels, raw material order of addition and hybrid mode
It optimizes, especially replaces the common carbomer940 of the prior art with CARBOPOL 974P, it is ensured that skin is saturating after replacement auxiliary material
The property crossed and pharmaceutical effectiveness performance do not subtract, and safety is higher.Since the technique that carbomer940 is benzene as the solvent used is given birth to
It produces, is easy output dissolvent residual, benzene toxicity is carcinogenic greatly, and 974p is produced with non-toluene solvent technique；The present invention provides
Formula not only more meet the requirement of pharmacopeia and relevant regulations, but also pass through the synergistic effect with other components, it can be ensured that solidifying
In the case that glue curative effect performance does not subtract, there is higher safety.
Specific embodiment
The following examples are used to illustrate the present invention, but are not intended to limit the scope of the present invention..
Embodiment 1
A kind of method for preparing metronidazole vagina gel is present embodiments provided, specially：
(1) 44g water is taken to dissolve 40g natrium adetate, 1.6kg CARBOPOL 974P is added in dispersion after dissolving completely, by material
It is added in vacuum homogeneous emulsifying machine, revolving speed controls 20r/min, stirs 4h, and temperature control is 40 DEG C during this, obtains gel base
Matter；
(2) sodium hydroxide is added in the gel-type vehicle, adjusting pH value is about 4.0, controls revolving speed 20r/min, stirring
30min obtains Blank gel；
(2) 64g methyl p-hydroxybenzoate and 16g propylparaben are added in 2.4kg propylene glycol, are heated molten
Solve propylene glycol solution；30g water is taken, is heated to 50 DEG C, the propylene glycol solution is added, adds 600g metronidazole, at 50 DEG C
Lower dissolution, obtains mixed solution；It after the mixed solution is cooled to 40 DEG C, is mixed with the Blank gel, vacuum homogeneous is added
In mulser, 2g water is added, stirs 2.5h, controls revolving speed 20r/min, temperature control is 40 DEG C during this, is obtained with finished product.
Embodiment 2
A kind of method for preparing metronidazole vagina gel is present embodiments provided, specially：
(1) 37.4g water is taken to dissolve 32g natrium adetate, 1.52kg CARBOPOL 974P is added in dispersion after dissolving completely, by object
Material is added in vacuum homogeneous emulsifying machine, and revolving speed controls 20r/min, stirs 4h, and temperature control is 40 DEG C during this, obtains gel
Matrix；
(2) sodium hydroxide is added in the gel-type vehicle, adjusting pH value is about 4.0, controls revolving speed 20r/min, stirring
30min obtains Blank gel；
(2) 56g methyl p-hydroxybenzoate and 16g propylparaben are added in 2.24kg propylene glycol, heating
Dissolve to obtain propylene glycol solution；25.6g water is taken, is heated to 50 DEG C, the propylene glycol solution is added, adds 592g metronidazole,
It is dissolved at 50 DEG C, obtains mixed solution；It after the mixed solution is cooled to 40 DEG C, is mixed with the Blank gel, vacuum is added
In homogeneous emulsifying machine, 2g water is added, stirs 2.5h, controls revolving speed 20r/min, temperature control is 40 DEG C during this, must be made into
Product.
Embodiment 3
A kind of method for preparing metronidazole vagina gel is present embodiments provided, specially：
(1) 56.2g water is taken to dissolve 48g natrium adetate, 1.68kg CARBOPOL 974P is added in dispersion after dissolving completely, by object
Material is added in vacuum homogeneous emulsifying machine, and revolving speed controls 20r/min, stirs 4h, and temperature control is 40 DEG C during this, obtains gel
Matrix；
(2) sodium hydroxide is added in the gel-type vehicle, adjusting pH value is about 4.0, controls revolving speed 20r/min, stirring
30min obtains Blank gel；
(2) 72g methyl p-hydroxybenzoate and 16g propylparaben are added in 2.4kg propylene glycol, are heated molten
Solve propylene glycol solution；38.4g water is taken, is heated to 50 DEG C, the propylene glycol solution is added, 608g metronidazole is added, 50
It is dissolved at DEG C, obtains mixed solution；It after the mixed solution is cooled to 40 DEG C, is mixed with the Blank gel, it is equal that vacuum is added
In matter mulser, 2g water is added, stirs 2.5h, controls revolving speed 20r/min, temperature control is 40 DEG C during this, is obtained with finished product.
Embodiment 4
A kind of method for preparing metronidazole vagina gel is present embodiments provided, compared with Example 1, difference is only that：
Methyl p-hydroxybenzoate and propylparaben are mixed and are added in propylene glycol, normal-temperature dissolution obtains propylene glycol solution；It will
The propylene glycol solution is mixed with normal-temperature water, is dissolved at normal temperature after metronidazole is added.
Embodiment 5
A kind of method for preparing metronidazole vagina gel is present embodiments provided, compared with Example 1, difference is only that：
The CARBOPOL 974P is replaced with carbomer940.
Embodiment 6
A kind of method for preparing metronidazole vagina gel is present embodiments provided, compared with Example 1, difference is only that：
Step (1) uncomfortable pH value reenters sodium hydroxide adjusting after step (3) mixes the mixed solution with the gel-type vehicle
PH value is 4.0.
Experimental example
1~6 the method for Example vaginal jellies being prepared and the metronidazole vagina gel original of listing grind sample
Product (lot number GDDL and lot number KAAU) are tested using artificial skin film according to following in vitro transdermal test method：
It (1) is 0.6cm by release area2Artificial skin film be fixed on Transdermal absorption instrument release pond one end, it is described artificial
The rough surface of skin membrane takes Metrogel test sample 0.15g to be spread evenly across the thick of the artificial skin film towards release pond
On matte；
(2) temperature for adjusting water in transdermal tester heat insulation trough is constant at 32 DEG C, and opens magnetic agitation；It is released described
It puts pond to be fixed on reception tank, 0.9% sodium chloride solution of 5ml is added in reception tank as receiving liquid, it is ensured that the artificial skin
The one side of the uncoated test sample of skin is contacted with the receiving liquid；It is fixed respectively at 0.5,1,2,3,4,5,6,7,8,9,10,12 hour
When sample 1ml, while the receiving liquid of equivalent equality of temperature is added；
(3) it after resulting reception sample filtering will be sampled, takes 50 μ l to inject high performance liquid chromatograph respectively, separately takes metronidazole
The solution of 6 μ g/ml is made for the transdermal measurement of artificial skin film, external standard method with receiving liquid dilution in appropriate reference substance
Metronidazole present in receiving liquid；Wherein, use octadecylsilane chemically bonded silica for filler, with volume ratio for 80：20 water-
Methanol is mobile phase, Detection wavelength 320nm；
(4) the Percutaneous permeability Q of drug is calculated according to following formula：Qn=(A sample/A to) × C is right × and V+ ∑ qi to be to calculate
The accumulative transit dose of test sample.Wherein, Qn be different moments add up transit dose (μ g), A sample be receiving liquid peak area, A to for pair
According to the peak area of product solution, for C to the concentration (μ g/ml) for reference substance solution, V corresponds to the volume of receiving liquid, and qi is that i-th is real
The transit dose of survey；
With the time (h) for abscissa, transit dose (μ g) is ordinate, carries out linear fit, calculates whether metronidazole meets
Zero order kinetics release rule such as meets the transdermal rule of zero level, compares the slope from triturate and former triturate.
The instrument used in the present embodiment includes：High performance liquid chromatograph：Shimadzu LC-20AT；Transdermal absorption instrument：Model
TT-6, Tianjin Zheng Tong Science and Technology Ltd.；Refiner：FSH-2, Jie Ruier Electrical Appliances Co., Ltd of Jintan City.
Wherein, the product data that embodiment 1 provides are as shown in table 1.
Table 1：Drug accumulation transit dose measurement result table (n=6)
| Sample time | 0.5h | 1h | 2h | 3h | 4h | 5h | 6h | 8h | 9h | 10h | 12h |
| Min(μg) | 0.4 | 1.0 | 3.1 | 8.0 | 12.2 | 17.2 | 21.7 | 28.9 | 37.4 | 42.4 | 65.9 |
| Max(μg) | 2.2 | 13.3 | 13.5 | 20.6 | 27.0 | 33.9 | 42.0 | 46.6 | 53.0 | 60.3 | 86.4 |
| AV(μg) | 1.2 | 4.9 | 7.5 | 13.1 | 18.7 | 24.2 | 30.3 | 36.9 | 43.9 | 50.4 | 74.4 |
| RSD% | 64% | 89% | 52% | 37% | 30% | 27% | 24% | 18% | 15% | 14% | 11% |
Through detecting, with the time (h) for abscissa, transit dose (μ g) is ordinate, carries out linear fit, and each embodiment provides
Gel and commercially available original grind the R of product2Value is all larger than 0.98, meets the transdermal rule of zero level；And it is produced obtained by various embodiments of the present invention
The slope of product and the slope of commercial product are close, illustrate that vaginal jellies transmitance provided by the invention is suitable with commercial product.This
It invents in each embodiment provided, Examples 1 to 3 effect is preferable, and 1 effect of embodiment is best.
Although above having used general explanation, specific embodiment and test, the present invention is made to retouch in detail
It states, but on the basis of the present invention, it can be made some modifications or improvements, this is apparent to those skilled in the art
's.Therefore, these modifications or improvements without departing from theon the basis of the spirit of the present invention, belong to claimed
Range.
Claims (9)
1. a kind of method for preparing metronidazole vagina gel, which is characterized in that include the following steps：
(1) natrium adetate is mixed with water, adds CARBOPOL 974P, sufficiently carried out vacuum emulsifying after swelling, obtain solidifying
Gel matrix；
(2) pH value for adjusting the gel-type vehicle is 4.0~4.5, obtains Blank gel；
(3) by methyl p-hydroxybenzoate and propylparaben with mass ratio 2~6:1 mixing is added in propylene glycol, obtains
Propylene glycol solution；The propylene glycol solution is mixed with water, metronidazole is added and sufficiently dissolves, then is sufficiently mixed with the Blank gel
Close to get.
2. the method according to claim 1, wherein by methyl p-hydroxybenzoate and propylparaben
With mass ratio 3.5~4.5:1 mixing is added in propylene glycol.
3. the method according to claim 1, wherein the metronidazole, methyl p-hydroxybenzoate and to hydroxyl
The mass ratio of yl benzoic acid propyl ester is 35~40：2~6:1.
4. according to the method described in claim 3, it is characterized in that, the metronidazole, methyl p-hydroxybenzoate and to hydroxyl
The mass ratio of yl benzoic acid propyl ester is 37~38：3.5~4.5：1.
5. method described in any one according to claim 1~4, which is characterized in that by methyl p-hydroxybenzoate and to hydroxyl
The mixing of yl benzoic acid propyl ester is added in propylene glycol, is heated to 45~55 DEG C of sufficiently dissolutions, obtains propylene glycol solution；
The propylene glycol solution is mixed with 45~55 DEG C of water, is dissolved at 45~55 DEG C after metronidazole is added.
6. the method according to claim 1, wherein being added in the gel-type vehicle when preparing gel-type vehicle
Sodium hydroxide, adjusting pH value is 4.0~4.5.
7. being comprised the following specific steps that according to the method described in claim 1, its spy is：
(1) 1~5 part of natrium adetate is mixed with water, adds 80~120 parts of CARBOPOL 974Ps, sufficiently carried out after swelling true
Empty emulsifying, obtains gel-type vehicle；
(2) it is 4.0~4.5 that sodium hydroxide is added in the gel-type vehicle and adjusts pH value, obtains Blank gel；
(2) 2~6 parts of methyl p-hydroxybenzoates and 0.5~1.5 part of propylparaben are added 130~160 parts the third two
In alcohol, propylene glycol solution is dissolved by heating to obtain；The propylene glycol solution is mixed with water, adds 35~40 parts of metronidazoles, sufficiently
Dissolve to obtain mixed solution；The mixed solution is mixed with the Blank gel, homogeneous stirring to get；
The total amount of water used in each step is 1~10 part.
8. being comprised the following specific steps that according to the method described in claim 7, its spy is：
(1) 2~3 parts of natrium adetates are mixed with water, adds 95~105 parts of CARBOPOL 974Ps, sufficiently carried out after swelling true
Empty emulsifying, obtains gel-type vehicle；
(2) it is 4.0~4.5 that sodium hydroxide is added in the gel-type vehicle and adjusts pH value, obtains Blank gel；
(3) 3.5~4.5 parts of methyl p-hydroxybenzoates and 0.5~1.5 part of propylparaben are added 140~150 parts
In propylene glycol, propylene glycol solution is dissolved by heating to obtain；The propylene glycol solution is mixed with water, adds 37~38 parts of metronidazoles,
Sufficiently dissolve to obtain mixed solution；The mixed solution is mixed with the Blank gel, homogeneous stirring to get；
The total amount of water used in each step is 4~6 parts.
9. the metronidazole vagina gel that claim 1~8 any one the method is prepared.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| 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 |
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| RO91013A2 (en) * | 1984-12-08 | 1987-02-27 | Intreprinderea De Produse Cosmetice"Nivea",Ro | VAGINAL GEL |
| CN104546689A (en) * | 2015-01-07 | 2015-04-29 | 北京紫光制药有限公司 | Medicine composition containing metronidazole |
| CN104922151A (en) * | 2015-07-22 | 2015-09-23 | 赵立 | Externally applied hydrogel preparation for women and preparing method thereof |
| WO2017117650A1 (en) * | 2016-01-10 | 2017-07-13 | Smilesonica Inc | Viscosity and stability modified ultrasound gel |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| 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 |
| WO2021036294A1 (en) * | 2019-08-28 | 2021-03-04 | 南京天朗制药有限公司 | Vaginal acid-base buffer gel and preparation method |
| CN110575431B (en) * | 2019-08-28 | 2021-08-03 | 南京天朗制药有限公司 | Vaginal acid-base buffer gel and preparation method thereof |
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