CN102240260A - Medicament for treating colpoxerosis and preparation method thereof - Google Patents
Medicament for treating colpoxerosis and preparation method thereof Download PDFInfo
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- CN102240260A CN102240260A CN 201110127574 CN201110127574A CN102240260A CN 102240260 A CN102240260 A CN 102240260A CN 201110127574 CN201110127574 CN 201110127574 CN 201110127574 A CN201110127574 A CN 201110127574A CN 102240260 A CN102240260 A CN 102240260A
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- rebamipide
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- 238000002360 preparation method Methods 0.000 title claims abstract description 12
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- Medicinal Preparation (AREA)
Abstract
The invention discloses a medicament for treating colpoxerosis and a preparation method thereof. 1,000 grams of gel is prepared from the following raw materials by weight: 10 to 20 grams of Rebamipide, 5 to 8 grams of Carbomer, 4 to 5 grams of sodium hyaluronate, 200 to 500 grams of polyethylene glycol 400, 1 to 2 grams of Edetate disodium, 18 to 22 grams of polysorbate 80, 1 to 10 grams of lactic acid, 1 to 3 grams of low polylactic acid, a proper amount of sodium hydroxide and the balance of water. The preparation method comprises the following steps of: (1) taking the Rebamipide for later use; (2) adding the polyethylene glycol 400 and the polysorbate 80 into the Rebamipide in the step (1) to obtain medicinal liquid for later use; (3) adding water into the Edetate disodium for later use; (4) mixing the polyethylene glycol 400 and the low polylactic acid uniformly by adding water; (5) adding the Carbomer and the sodium hyaluronate into the step (4) to form a gel matrix for later use; and (6) adding the lactic acid into the medicinal liquid to obtain the gel preparation. After the medicament for treating colpoxerosis is used for a period of time through vaginal administration, the colpoxerosis can be cured, so that the defects of the known technique can be overcome.
Description
Technical field
The present invention relates to medicine, is a kind of medicine for the treatment of vaginal dryness disease and preparation method thereof.
Background technology
Vaginal dryness disease is that the glycoprotein diacrisis in vagina epithelium tissue and the mucosal tissue causes common sympton: dry and astringent, scorching hot, no secretions etc., and all kinds of gynaecopathias of easy infection.Because vaginal dryness is a kind of commonly encountered diseases, therefore, the technical scheme that those skilled in the art's research always for many years provides is to adopt the vaginal lubrication relief of symptoms.Though, this class lubricating fluid has many kinds, but, these lubricating fluids only are that vagina surface is lubricated, and therefore, these lubricants are without any therapeutical effect, can't improve the situation of the glycoprotein diacrisis in vagina epithelium tissue and the mucosal tissue, and these lubricants need life-time service, and these lubricants of life-time service also have deficiencies such as pollution, bacterial infection and injury organ.
Summary of the invention
The objective of the invention is, a kind of medicine for the treatment of vaginal dryness disease and preparation method thereof is provided, it uses certain time limit to reach and cures dry and astringent disease by vagina administration, thereby overcomes the deficiency of known technology.
The present invention for achieving the above object, realize by following scheme: a kind of medicine for the treatment of vaginal dryness disease, the gel of every 1000g is made by the raw material of following weight ratio: rebamipide 10-20g, carbomer 5-8g, hyaluronic acid sodium 4-5g, PEG400 200-500g, disodium edetate 1-2g, polyoxyethylene sorbitan monoleate 18-22g, lactic acid 1-10g, lact-acid oligomer 1-3g, sodium hydroxide is an amount of, and surplus is a water.
A kind of medicine for the treatment of vaginal dryness disease of the present invention, the gel of every 1000g is made by the raw material of following weight ratio: rebamipide 15g, carbomer 8g; Hyaluronic acid sodium 5g, PEG400 300g, disodium edetate 2g, polyoxyethylene sorbitan monoleate 20g, lactic acid 3g, lact-acid oligomer 2g, sodium hydroxide is an amount of, and surplus is a water.
A kind of medicine for the treatment of vaginal dryness disease of the present invention, the gel of every 1000g is made by the raw material of following weight ratio: rebamipide 20g, carbomer 5g; Hyaluronic acid sodium 4g, PEG400 500g, disodium edetate 2g, polyoxyethylene sorbitan monoleate 20g, lactic acid 2g, lact-acid oligomer 1g, sodium hydroxide is an amount of, and surplus is a water.
A kind of preparation method for the treatment of the medicine of vaginal dryness disease of the present invention comprises the steps:
1. it is standby to 0.5-10um to get rebamipide 10-20g porphyrize by weight;
2. by weight taking polyethylene glycol 400 200-500g 20% with polyoxyethylene sorbitan monoleate 18-22g mixing after add in the medicine of step in 1. and be ground to evenly, it is standby to obtain pharmaceutical liquid;
3. get disodium edetate 1-2g by weight, add the water heating for dissolving of 100-120g, standby;
4. 80% and lact-acid oligomer 1-3g by weight taking polyethylene glycol 400 200-500g adds entry 330-640g mixing;
5. get carbomer 5-8g, hyaluronic acid sodium 4-5g by weight and slowly join in the mixture of step in 4. and fully stir, make its swelling, adding an amount of sodium hydroxide solution adjust pH after being uniformly dispersed again is 3-5, and stirring, it is standby to form gel-type vehicle;
6. the pharmaceutical liquid of step in 2. slowly added in the step gel-type vehicle 5., after stirring, make medicinal liquid evenly spread in the gel-type vehicle after, join in above-mentioned medicinal liquid and the gel-type vehicle by weight extracting lactic acid 1-10g again, adjust pH obtains the gel preparation product to 3-5.
Medicine vagina administration of the present invention, the part can obtain higher drug level, directly acts on the goblet cell of vaginal mucosa and vaginal epithelial cell, and targeting is strong, evident in efficacy and drug safety height; Easy to use, good absorbing; Has good moisture-keeping function; Smooth property is good; Have that adhesiveness is good, the characteristics of good fluidity, can bring into play therapeutical effect immediately after the administration, release is fast; But the holdup time of gel prolong drug makes lasting medicine, and can regulate the pH value of vagina, makes vagina be in a kind of sour environment, avoids destroying the microenvironment balance of vagina.
Medicine of the present invention owing to be at the pathogeny of vaginal dryness disease and the technical scheme of physiological characteristics proposition, therefore, have good therapeutical effect, and has no side effect, and stingless excitation, cure rate reach about 80-90%.
Because vaginal dryness disease is that its epithelial tissue and mucosal tissue cause unusually, and the effect of medicine of the present invention is to repair the vaginal mucosa tissue.Pharmacodynamics test shows that medicine of the present invention can obviously increase the secretion of the mucoprotein mucoitin of vagina, has promoted form, growth, differentiation and the secretory function of goblet cell.The clinical statistics data shows: medicine of the present invention is administered once every day, and each 5g inserts intravaginal, per 21 days is a course of treatment, uses 1 drug withdrawal course of treatment 7 days, experimenter 121 people, using the obvious effective rate of 1 course of treatment is 100%, use 2 courses of treatment, transference cure persons such as vagina is slightly dry and astringent, burning sensation, dyspareunia are 92.6%, use 3 courses of treatment, recovering the normal secretory function person of vagina is 89.8%, drug safety height of the present invention, nonirritant can life-time service.
The pharmacodynamics test of medicine of the present invention is reported as follows:
1, experiment purpose
Adopt surgical removal doe bilateral ovaries, be intended to set up the rabbit vaginal dryness disease model that to simulate climacteric nature pathological process, detect the variation of the rebamipide treatment mucoprotein Muc-5ae in front and back.
2, medicine
2.1 experiment medicine
The medicine of treatment vaginal dryness disease, content of dispersion is 2%, lot number is respectively 20101007, is provided by the Shandong Prov. Medical Apparatus ﹠ Instrument Research Inst.
The component of the medicine of treatment vaginal dryness disease: rebamipide 20g, carbomer 5g, hyaluronic acid sodium 5g, propylene glycol 500g, disodium edetate 1g, polyoxyethylene sorbitan monoleate 20g, lactic acid 2g, lact-acid oligomer 3g, sodium hydroxide is an amount of, adds water to 1000g.Add in the example
Matched group: medical chitose (20 mg/ml), lot number 20100803, it wins the production of biological product company limited by Shanghai.
The Muc-5ac monoclonal antibody is produced by company of China fir Golden Bridge in Beijing.SABC result adopts the Tongji Medical Institute's thousand screen image HMIAS-2000 of company image analysis system analyses.
3, animal: Japan large ear rabbit
3.1 source: purchase anti-medical limited company animal center in the Shandong, Shandong.Credit number: the SCXK(Shandong) 2,010 0002.
3.2 body weight: 2.0-2.5kg
3.3 sex: female (unpregnancy), healthy no disease.
3.4 number of animals: 128
3.5 zoopery room environmental: 20~24 ℃ of temperature; Humidity 40%~70%; The cage tool, Fengqiao Purifying Equipment Factory, xin District, Suzhou, credit number: SCXK (Soviet Union) 2002-0034.
3.6 feed resource: Shandong Province's Experimental Animal Center, the moving word 200001001 of raising in Shandong
4, route of administration: transvaginal administration
5, method
5.1 experiment grouping
Animal is divided into 4 groups at random by body weight, the normal control group, medicine group 2%, the chitosan of the dry and astringent disease group of modeling, treatment vaginal dryness disease contrast the glue group, 32 every group with fixed attention.
5.2 experiment modeling
Except that the normal control group, all the other 3 groups of modelings in the following manner.The preceding 12 h fasting water of rabbit art.Hind leg thigh outside muscle iodophor disinfection, ketaject injection 30 mg/kg body constitution amount intramuscular anesthesias.Get dorsal position, extremity open and are fixing.The hypogastric region agent of shedding is shedded, iodophor disinfection, and the shop aseptic towel is single, successively cuts through median abdominal incision and enters the abdominal cavity, and the excision bilateral ovaries is sent histological examination, and operation technique all carries out under aseptic condition, spay, postoperative is sewed up each layer of stomach wall continuously.Equal intravenous drip normal saline 100 mL in the art, in add penicillin pin 400,000 U, postoperative is intramuscular injection penicillium sp rope pin 400,000 U for three days on end, prevention infection.Feed with conventional feed for every.Avoid to contain nursings such as the higher Semen sojae atricolor of plant estrogen, Rhizoma Dioscoreae.
5.3 administration
According to the rabbit vagina volume, the medicine group 2% and the chitosan group vagina administration amount of treatment vaginal dryness disease are 1.0g, inject in two groups of rabbit vaginas with administrator, make animal keep the high low level of buttocks passive quiet 3 minutes after the administration.Weekly 21 days phases, be administered once every day, successive administration 21 days.Treat 3 cycles.Observe after the drug withdrawal.
5.4 specimen sampling and detection
Laboratory animal is checked by same people.Review time, place, brightness of illumination and temperature are identical.In (1) the 1st cycle, after administration the 7th, 14,21 day, get 4 rabbits every group of each time point respectively; The 21st day time point in the 2nd cycle got 4 rabbits; The 21st day time point in the 3rd cycle got 4 rabbits; (2) after the drug withdrawal the 7th, 14,21 day, get 4 rabbits at each time point respectively; Behind air tap inserting method execution animal, get the vaginal mucosa tissue, conventional paraformaldehyde is fixed, and specimens paraffin embedding slices adopts the dyeing of Muc-5ac monoclonal antibody immunity group.
5.5 graphical analysis and statistical procedures
Use the HMIAS-2000 image analysis system, under 400 times of visuals field, 5 visuals field of every section picked at random are detected conjunctival epithelium Muc-5ac immunohistochemical staining positive reaction thing, measure positive reaction thing average gray value.The Muc-5ac positive expression at most color depth, gray value is little, on the contrary then gray value is big.Muc-5ac positive expression coloring site is the kytoplasm of goblet cell, dyes to be pale brown color fine particulate.Use SAS 8.1 statistical packages, to the capable variance analysis of objective sign numerical value before and after each group treatment.
6, experimental result
Each group treatment back Muc-5ac monoclonal antibody immunity groupization
The analysis of dyeing gray value (x ± s)
Muc-5ac monoclonal antibody immunity group dyeing vagina topical treatment 7 days, 14 days, 21 days, 42 days, 63 days, the medicine group 2% of treatment vaginal dryness disease compares with chitosan group and the dry and astringent disease group of modeling, the painted gray value of Muc-5ac monoclonal antibody immunity groupization obviously reduces, its difference has utmost point significance meaning (P<0.01), obviously increase promptly for the Muc-5ac secretory volume of the medicine group of treatment vaginal dryness disease, secretory volume increases.After the medicine that adopts treatment vaginal dryness disease is described, vaginal epithelial cell increases obviously mucoprotein secretory volume, treat 21 days continuously after, mucoprotein (Muc-5ac) secretory volume reaches 89.1% of normal value, observe 21 days after the drug withdrawal, mucoprotein secretory volume remains on this scope always.The chitosan matched group can improve mucoprotein secretory volume slightly, and it is poor that therapeutic effect is treated the medicine of vaginal dryness disease, mainly based on outside lubrication.
7, conclusion
Experimental result shows, the medicine group of treatment vaginal dryness disease is compared with vaginal dryness modeling group (not administration group), the medicine group of treatment vaginal dryness disease can obviously increase the secretion of the mucoprotein Muc-5ae of vagina, form, growth, differentiation and the secretory function of goblet cell have been promoted, treat 3 all after dates, the secretory volume of mucoprotein Muc-5ae reaches 89.1% of normal value, observes 21 days after the drug withdrawal, and mucoprotein secretory volume remains on this scope always.The chitosan group promotes that the excretory effect of mucoprotein Muc-5ae is relatively poor; The medicine of therefore treating vaginal dryness disease is the pharmaceutical preparation of a kind of comparatively ideal treatment vaginal dryness disease obvious results.
The medicine irritation test report of treatment vaginal dryness disease of the present invention is as follows:
1, experiment purpose
After observing the medicine rabbit vagina single of auspicious treatment vaginal dryness disease and multiple dosing whether vaginal mucosa is produced irritant reaction, for data for clinical drug use provides foundation.
2, medicine
2.1 title: the medicine of 2% treatment vaginal dryness disease: the milky translucent gels, lot number 20100902 is provided by the Shandong Prov. Medical Apparatus ﹠ Instrument Research Inst.
2.2 blank substrate: water white transparency, lot number: 20100902, provide by the Shandong Prov. Medical Apparatus ﹠ Instrument Research Inst.
3, animal: rabbit
3.1 source: purchase anti-medical limited company animal center in the Shandong, Shandong.Credit number: the SCXK(Shandong) 2,008 0002.
3.2 body weight: 1.5~2.0 kg
3.3 sex: female
3.4 number of animals: 32
3.5 zoopery room environmental: temperature 20-24 ℃; Humidity 40%-70%; The cage tool, Fengqiao Purifying Equipment Factory, xin District, Suzhou, credit number: SCXK (Soviet Union) 2002-0034.
3.6 feed resource: Shandong Province's Experimental Animal Center, the moving word 200001001 of raising in Shandong
4. route of administration: vagina administration
5. method
5.1 single-dose
Get 16 rabbit and be divided into two groups at random, be respectively the medicine group and the blank matrix group of treatment vaginal dryness disease, 8 every group by body weight.According to the rabbit vagina volume, get the medicine group and the blank matrix group of 1.0g treatment vaginal dryness disease, inject with administrator and respectively organize in the rabbit vagina, make animal keep the high low level of buttocks passive quiet 3 minutes after the administration.Put to death zootomy in 24 hours after the administration, observe the medication local mucous membrane and have or not irritant reaction such as hyperemia, redness.
5.2 multiple dosing
Get 16 rabbit and be divided into two groups at random, be respectively the medicine group and the blank matrix group of treatment vaginal dryness disease, 8 every group by body weight.According to the rabbit vagina volume, get the medicine group and the blank matrix group of 1.0g treatment vaginal dryness disease, inject with administrator and respectively organize in the rabbit vagina, make animal keep the high low level of buttocks passive quiet 3 minutes after the administration.Once a day, successive administration is 7 days.Put to death zootomy in 24 hours after the last administration, get vagina and vertically cut to observe and have or not irritant reaction such as hyperemia, redness, mucosal ulcer and abnormal secretion thing.
6. result
The gross anatomy perusal: the single vagina administration, dissected animal in 24 hours behind the medicine, the perusal vaginal mucosa is not seen irritative responses such as obvious hyperemia, edema, does not see notable difference with blank matrix group.Multiple dosing group, successive administration were dissected rabbit vagina mucosa perusal vaginal mucosa and are not seen irritant reaction such as obvious hyperemia, edema, mucosal ulcer and abnormal secretion thing after 1 week, relatively showed no obvious abnormalities with blank matrix group.Pathological examination: epithelium is not seen and is obviously thickened and hypertrophy, does not see morphological changes such as obvious degeneration, necrosis yet.No obvious blood vessel hyperplasia, hyperemia in the mucosa are compared Non Apparent Abnormality with blank matrix group.
7. conclusion
The medicine single and the repeatedly rabbit vagina administration of 2% treatment vaginal dryness disease, animal generally in order, unusual performance such as no restlessness after the administration, dissect the vagina perusal and do not see stimulations such as obvious hyperemia, redness, mucosal ulcer and abnormal secretion thing, histopathologic examination: epithelium is not seen and is obviously thickened and hypertrophy, does not see morphological changes such as obvious degeneration, necrosis yet.No obvious blood vessel hyperplasia, hyperemia in the mucosa are compared Non Apparent Abnormality with blank matrix group.
The specific embodiment
Embodiment:
The medicine of treatment vaginal dryness disease of the present invention, this medicine is a gel, and every 1000g gel is made by the raw material of following weight ratio: rebamipide 10-20g, carbomer 5-8g, hyaluronic acid sodium 4-5g, PEG400 200-500g, disodium edetate 1-2g, polyoxyethylene sorbitan monoleate 18-22g, lactic acid 1-10g, lact-acid oligomer 1-3g, sodium hydroxide is an amount of, and surplus is a water.
PEG400 in the medicine material of the present invention can adopt ethanol, ethylene glycol, propylene glycol or glycerol to substitute.
Medicine of the present invention can have multiple compound mode:
1, rebamipide 15g, carbomer 8g, hyaluronic acid sodium 5g, ethylene glycol 300g, disodium edetate 2g, polyoxyethylene sorbitan monoleate 20g, lactic acid 3g, lact-acid oligomer 2g, sodium hydroxide is an amount of, adds water to 1000g.
2, rebamipide 20g, carbomer 5g, hyaluronic acid sodium 4g, PEG400 500g, disodium edetate 2g, polyoxyethylene sorbitan monoleate 20g, lactic acid 2g, lact-acid oligomer 1g, sodium hydroxide is an amount of, adds water to 1000g.
3, rebamipide 17g, carbomer 8g, hyaluronic acid sodium 5g, glycerol 450g, disodium edetate 1.5g, polyoxyethylene sorbitan monoleate 20g, lactic acid 10g, lact-acid oligomer 1g, sodium hydroxide is an amount of, adds water to 1000g.
4, rebamipide 10g, carbomer 7g, hyaluronic acid sodium 4g, ethanol 500g, disodium edetate 2g, polyoxyethylene sorbitan monoleate 18g, lactic acid 1g, lact-acid oligomer 2g, sodium hydroxide is an amount of, adds water to 1000g.
5, rebamipide 18g, carbomer 5g, hyaluronic acid sodium 4.5g, ethanol 350g, disodium edetate 1g, Polysorbate 22g, lactic acid 8g, lact-acid oligomer 1.5g, sodium hydroxide is an amount of, adds water to 1000g.
6, rebamipide 19g, carbomer 6g, hyaluronic acid sodium 5g, ethanol 460g, disodium edetate 2g, polyoxyethylene sorbitan monoleate 21g, lactic acid 9g, lact-acid oligomer 1g, sodium hydroxide is an amount of, adds water to 1000g.
7, rebamipide 12g, carbomer 5g, hyaluronic acid sodium 7g, ethylene glycol 200g, disodium edetate 2g, polyoxyethylene sorbitan monoleate 20g, lactic acid 7g, lact-acid oligomer 1g, sodium hydroxide is an amount of, adds water to 1000g.
8, rebamipide 14g, carbomer 6.5g, hyaluronic acid sodium 4.5g, glycerol 260g, disodium edetate 1.5g, polyoxyethylene sorbitan monoleate 19.5g, lactic acid 6g, lact-acid oligomer 1.5g, sodium hydroxide is an amount of, adds water to 1000g.
9, rebamipide 20g, carbomer 5g, hyaluronic acid sodium 5g, propylene glycol 500g,, disodium edetate 1g, polyoxyethylene sorbitan monoleate 20g, lactic acid 2g, lact-acid oligomer 3g, sodium hydroxide is an amount of, adds water to 1000g.
The sodium hydroxide that uses in the above-mentioned component is used for adjust pH, transfers to 3-5 for suitable with pH value.
The embodiment of above-mentioned various components all can make according to following method:
1. it is standby to 0.5-10um to get rebamipide 10-20g porphyrize by weight;
2. by weight taking polyethylene glycol 400 200-500g 20% with polyoxyethylene sorbitan monoleate 18-22g mixing after add in the medicine of step in 1. and be ground to evenly, it is standby to obtain pharmaceutical liquid;
3. get disodium edetate 1-2g by weight, add the water heating for dissolving of 100-120g, standby;
4. 80% and lact-acid oligomer 1-3g by weight taking polyethylene glycol 400 200-500g adds entry 330-640g mixing;
5. get carbomer 5-8g, hyaluronic acid sodium 4-5g by weight and slowly join in the mixture of step in 4. and fully stir, make its swelling, adding an amount of sodium hydroxide solution adjust pH after being uniformly dispersed again is 3-5, and stirring, it is standby to form gel-type vehicle;
6. the pharmaceutical liquid of step in 2. slowly added in the step gel-type vehicle 5., after stirring, make medicinal liquid evenly spread in the gel-type vehicle after, join in above-mentioned medicinal liquid and the gel-type vehicle by weight extracting lactic acid 1-10g again, adjust pH obtains the gel preparation product to 3-5.
Claims (4)
1. medicine for the treatment of vaginal dryness disease, it is characterized in that: this medicine is a gel, and the gel of every 1000g is made by the raw material of following weight ratio: rebamipide 10-20g, carbomer 5-8g, hyaluronic acid sodium 4-5g, PEG400 200-500g, disodium edetate 1-2g, polyoxyethylene sorbitan monoleate 18-22g, lactic acid 1-10g, lact-acid oligomer 1-3g, sodium hydroxide is an amount of, and surplus is a water.
2. a kind of medicine for the treatment of vaginal dryness disease according to claim 1, it is characterized in that: the gel of every 1000g is made by the raw material of following weight ratio: rebamipide 15g, carbomer 8g; Hyaluronic acid sodium 5g, PEG400 300g, disodium edetate 2g, polyoxyethylene sorbitan monoleate 20g, lactic acid 3g, lact-acid oligomer 2g, sodium hydroxide is an amount of, and surplus is a water.
3. a kind of medicine for the treatment of vaginal dryness disease according to claim 1, it is characterized in that: the gel of every 1000g is made by the raw material of following weight ratio: rebamipide 20g, carbomer 5g; Hyaluronic acid sodium 4g, PEG400 500g, disodium edetate 2g, polyoxyethylene sorbitan monoleate 20g, lactic acid 2g, lact-acid oligomer 1g, sodium hydroxide is an amount of, and surplus is a water.
4. each described a kind of preparation method for the treatment of the medicine of vaginal dryness disease of claim 1-3 is characterized in that: comprise the steps:
1. it is standby to 0.5-10um to get rebamipide 10-20g porphyrize by weight;
2. by weight taking polyethylene glycol 400 200-500g 20% with polyoxyethylene sorbitan monoleate 18-22g mixing after add in the medicine of step in 1. and be ground to evenly, it is standby to obtain pharmaceutical liquid;
3. get disodium edetate 1-2g by weight, add the water heating for dissolving of 100-120g, standby;
4. 80% and lact-acid oligomer 1-3g by weight taking polyethylene glycol 400 200-500g adds entry 330-640g mixing;
5. get carbomer 5-8g, hyaluronic acid sodium 4-5g by weight and slowly join in the mixture of step in 4. and fully stir, make its swelling, adding an amount of sodium hydroxide solution adjust pH after being uniformly dispersed again is 3-5, and stirring, it is standby to form gel-type vehicle;
6. the pharmaceutical liquid of step in 2. slowly added in the step gel-type vehicle 5., after stirring, make medicinal liquid evenly spread in the gel-type vehicle after, join in above-mentioned medicinal liquid and the gel-type vehicle by weight extracting lactic acid 1-10g again, adjust pH obtains the gel preparation product to 3-5.
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CN104771790A (en) * | 2014-01-13 | 2015-07-15 | 成都英诺新科技有限公司 | Midwifery gel preparation method |
CN105982989A (en) * | 2015-01-27 | 2016-10-05 | 深圳市佳泰药业股份有限公司 | Sanitary lotion and preparation method thereof |
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