CN102688182B - Vagina pH buffer antibacterial gel and preparation method thereof - Google Patents

Abstract

The invention provides vagina pH buffer antibacterial gel, a preparation method thereof, and a using method thereof. The gel mainly comprises the components of polycarbophil, carbomer, ethylenediamine tetraacetic acid disodium, chitosan, glycerol, triethanolamine, methyl parahydroxybenzoats and deionized water. By using the weak acidity of polycarbophil and the antibacterial performance of chitosan, the gel can eliminate the source of recurrence of vagina inflammatory diseases and recovers the self-cleaning ability of the vagina. The gel is free from antigen performance, allergy and irritation, and convenient to use, and tissue reaction is avoided.

Description

A kind of vaginal pH buffering antibacterial gel and preparation method thereof

Technical field

The present invention relates to a kind of vaginal pH buffering antibacterial gel and preparation method thereof.

Background technology

All vaginitiss are all by certain pathogen, such as the infection such as trichomonal vaginitis, Candida albicans, streptococcus cause.But in normal situation, vaginal pH is in 3.8-4.4, can suppress the Growth and Reproduction of these pathogens, namely has self-purification function, even thereby infected above-mentioned these pathogens, can not cause inflammation yet.But in case vaginal environment is destroyed, pH value is unbalance, these pathogens will amount reproduction, causes inflammation.Thereby, the treatment vaginitis, must balance in environment, recover the pH value of vagina, fundamentally eliminate the living environment of pathogen.But, current treatment is to rely on merely Drug therapy mostly, no matter is oral antibiotic, or suppository class vaginal suppository class, or vaginal lotion class, if use separately, can kill pathogenic bacterium, but this treatment is " curing the symptoms, not the disease ", although inflammation has been alleviated, but in case discontinue medication, remaining pathogen will soon amount reproduction, makes the inflammation recurrence.The part patient is because vaginal symptoms is eased or eliminates after treatment, and disease is not yet thoroughly cured, and when the pH value of vagina changed, vaginitis will recur again.

Existing colpitic method or the medicine of being used for the treatment of, easily produce drug resistance and be symptomatic treatment.Fundamentally do not solve the root of vaginitis recurrence.Vaginitis easily recurrence largely goes on the market because the destruction of the unbalance and intravaginal environment of pH value.

Polycarbophil has more stable faintly acid and, to the good adhesion of mucosa, makes gel preparation for intravaginal, can make the intravaginal pH value be in normal level, makes to cause the antibacterial of inflammation to lose the environment of growth, effectively prevention of inflammation recurrence.Polycarbophil is applied to the luxuriant and rich with fragrance gel of the clinical fragrant plant that the grand production of Hainan emperor is arranged at present, main component be Polycarbophil, only for the buffering and the balance vagina PH value, do not add antimicrobial component, still need to coordinate with antibiotic and antifungal drug treatment, medicine is repeatedly treated and must be brought drug resistance and larger side effect.

Summary of the invention

The invention provides a kind of vaginal pH buffering antibacterial gel and preparation method thereof.

PH value buffering antibacterial gel of the present invention comprises following component, by weight percentage:

Described chitosan is water-soluble chitosan.

Polycarbophil used in the present invention is produced by U.S. promise reputation company (Noveon.Inc), and its model is AA-1.

Utilize the anti-microbial property of Polycarbophil faintly acid and chitosan to solve the easily root of recurrence of colpitis, recover the vagina self-purification function.

Chitosan is a kind of natural bioactive material, the natural biological antibacterial, has no drug resistance, and it is worthy of note especially in solution after dissolving and contains amino (NH ²⁺), these amino passing through in conjunction with the negatron anti-bacteria.

Carbomer is produced by Nanjing WeiEr chemical engineering Co., Ltd, and its physico-chemical parameter meets No. 428401st, the accurate word (2005) of Soviet Union's medicine.

No. 428401st, the accurate word (2005) of table 1 Soviet Union's medicine

The pH value of vaginal pH buffering antibacterial gel of the present invention is 3.8-4.4, has powerful pH buffer capacity, can help the intravaginal environment to recover rapidly the pH balance.The present invention has acid formula, is conducive to promote the vagina self purification, and the rejection condition pathogenic bacterium reduce diseased plant group's assembly.Vaginal pH buffering antibacterial gel of the present invention is a kind of bioadhesive gel of high-moisture based on Polycarbophil, hydrophilic and water insoluble.But this gel tight adhesion, on the vaginal epithelial cell surface, forms the moistening film of one deck, for vaginal mucosa is supplemented large quantity of moisture.Safeguard that vagina is natural moist, protection vaginal walls elasticity.Polycarbophil of the present invention can form hydrogen bond with the mucin of vagina epithelium tissue, produce stronger mucus gel networks, thereby tight adhesion is in the vaginal wall epithelial cell.The normal vaginal epithelial cell update cycle is 3 days, and when the vaginal epithelial cell apoptosis came off, this gel just can come off thereupon, useful effect 72 hours.Chitosan used in the present invention belongs to non-stripping property antibacterial, and can not induce and produce the drug resistance bacterium, pure natural biological product, degradable is nontoxic, non-stimulated, have no drug resistance.

The preparation method of vaginal pH buffering antibacterial gel of the present invention comprises the steps:

(1) by proportioning, take Polycarbophil and carbomer, add in the glycerol taken by proportioning, dispersed with stirring to pasty state obtains the glycerol pasty liquid;

(2) by proportioning, take chitosan, add in deionized water, add disodiumedetate, methyl parahydroxybenzoate, stir and make each components dissolved, obtain chitosan solution;

(3) chitosan solution is added in the glycerol pasty liquid, stir, with triethanolamine solution, its pH is adjusted to 3.8-4.4, obtain the gel of Polycarbophil and chitosan;

(4) stop stirring discharging;

(5) fill;

(6) aseptic process.

PH value buffering antibacterial gel of the present invention has following advantage:

1. adjusting vaginal pH: make vagina recover normal acid-base value.Environment in repairing.

2. no antigen: for the polysaccharide composition, without protein, without immunoreation;

3. without irritated, non-stimulated: Polycarbophil is safe to human body;

4. easy to use: sterile product coordinates vaginal administration device to use;

5. inorganization reaction.

The specific embodiment

Embodiment 1

Above-mentioned percent is percetage by weight.

By proportioning, take Polycarbophil and carbomer, add in the glycerol taken by proportioning, dispersed with stirring to pasty state obtains the glycerol pasty liquid; By proportioning, take carboxymethyl chitosan, add in deionized water, add disodiumedetate, stir and make each components dissolved to clarification, obtain the carboxymethyl chitosan sugar juice; The carboxymethyl chitosan sugar juice is added in the glycerol pasty liquid, stir, with triethanolamine solution, its pH is adjusted to 3.8-4.4, obtain the gel of Polycarbophil and carboxymethyl chitosan; Stop stirring discharging; Fill; After aseptic process, obtain pH value buffering antibacterial gel of the present invention.

Embodiment 2

By proportioning, take Polycarbophil and carbomer, add in the glycerol taken by proportioning, dispersed with stirring to pasty state obtains the glycerol pasty liquid; By proportioning, take carboxymethyl chitosan, add in deionized water, add EDTA-2na, stir and make each components dissolved to clarification, obtain the carboxymethyl chitosan sugar juice; The carboxymethyl chitosan sugar juice is added in the glycerol pasty liquid, stir, with triethanolamine solution, its pH is adjusted to 3.8-4.4, obtain the gel of Polycarbophil and carboxymethyl chitosan; Stop stirring discharging; Fill; After aseptic process, obtain pH value buffering antibacterial gel of the present invention.

Embodiment 3

Above-mentioned percent is percetage by weight.

By proportioning, take Polycarbophil and carbomer, add in the glycerol taken by proportioning, dispersed with stirring to pasty state obtains the glycerol pasty liquid; By proportioning, take chitosan, add in deionized water, add EDTA-2na, stir and make each components dissolved to clarification, obtain chitosan solution; Chitosan solution is added in the glycerol pasty liquid, stir, with triethanolamine solution, its pH is adjusted to 3.8-4.4, obtain the gel of Polycarbophil and chitosan; Stop stirring discharging; Fill; After aseptic process, obtain vagina PH value buffering antibacterial gel of the present invention.Anti-(pressing down) bacterium rate detects

According to GB15979-2002, three embodiment of the present invention are resisted to the test of (pressing down) bacterium, three result of the tests are referring to table 2-4, vaginal pH buffering antibacterial gel of the present invention effect 2 minutes, 5 minutes, 10 minutes, 20 minutes and staphylococcus aureus, escherichia coli and Candida albicans, its killing rate all is greater than 50%, and product has antibacterial action.

Table 2 embodiment 1 bacteriostatic experiment result

Table 3 embodiment 2 bacteriostatic experiment results

Table 4 embodiment 3 bacteriostatic experiment results

Local irritation detects

Purpose: estimate pH value buffering antibacterial gel zest

Method: act on rabbit vagina with pH value buffering antibacterial gel (hereinafter to be referred as gel), observe its zest complete to rabbit and damaged vaginal mucosa.

Test material: pH value buffering antibacterial gel sample (lot number 20110104), 3g/ prop up

Contrast: carbomer gel (not containing Polycarbophil and chitosan) (irritant test)

Experimental animal: 24 of white big ear rabbits.

Get 24 of healthy white rabbit, female, be divided at random 4 groups of gel group, contrast complete vagina group and damaged vagina groups, 6 every group.Gel group and the complete vagina group of contrast, in the vagina 2cm place of each animal, use the syringe with the gavage syringe needle slowly to inject respectively gel 1g, carbomer gel 1g.Gel group and the damaged vagina group of contrast, inserted vagina 2cm with the circular file of the blunt circle of front end respectively in first 12 hours in administration, passes in and out 5 times, and friction causes the vagina breakage, and degree of injury should be consistent.Afterwards more as stated above respectively at animal vagina injection testing gel and carbomer gel.Observed in every 30 minutes once, complementary testing gel and carbomer gel.Guarantee that contact 4 hours every day at least with vaginal mucosa.

Continuous 7 days.

After 7 days, observe the animal pudendum and have or not hyperemia, erythema, edema or secretions etc.

Put to death animal, win vagina, have or not the irritative response symptoms such as hyperemia, erythema and edema with the clean rear perusal mucosa of normal saline flushing.Carry out the zest evaluation.Afterwards with 10% formalin fix, dehydration, waxdip, embedding, section, HE dyeing, under light microscopic, carry out pathological examination.

The irritation test viewing duration, the complete vagina group of gel and damaged vagina group diet, activity are all normal, without the phenomena of mortality.Mucomembranous surface is smooth, without edema, petechia, ulcer or abnormal response.Damaged group has an animal a small amount of secretions, vaginal mucosa irritation reaction to be arranged referring to table 5-7, and its average product score value was respectively 0 minute and 0.17 minute.With matched group, compare no significant difference.

Table 5 embodiment 1 vaginal mucosa irritation result of the test

Table 6 embodiment 2 vaginal mucosa irritation result of the tests

Table 7 embodiment 3 vaginal mucosa irritation result of the tests

Annotate: 0 without erythema, edema, secretions

1 very slight erythema, edema (almost can not discover), secretions

2 slight erythema, edema (exposed region is apparently higher than neighboring area), slight secretions

3 is poisoning to severe erythema, edema (protruding about 1mm), moderate secretions

The serious erythema of 4-6, edema (protrusion is greater than 1mm), a large amount of secretions

Testing result: during irritation test, gel treated animal diet, activity are all normal, and without the phenomena of mortality, animal vaginal mucosa smooth surface is glossy, without edema, petechia, ulcer or paraplasm, vaginal mucosa irritation reaction and matched group comparing difference nonsignificance; The pathological examination result, the complete vagina group of gel, damaged vagina treated animal inner membrance are complete, and epithelium is high column, comes off and inflammatory cells in a large number without downright bad, and the minority animal inner membrance of damaged vagina group is the doll shape.There is limitation incomplete, above-mentioned two groups and corresponding matched group comparing difference nonsignificance.

Conclusion: gel is to the vaginal mucosa nonirritant.

Sensitization detects

Purpose: estimate pH value buffering antibacterial gel zest and anaphylaxis

Method: the Buehler method acts on the Cavia porcellus vagina, observes its anaphylaxis.

Experiment material: pH value buffering antibacterial gel embodiment 1 sample, 3g/ prop up; Embodiment 2 samples, 3g/ prop up; Embodiment 3 samples, 3g/ prop up.

Positive control (hypersensitive test) DNFB (chemical pure) Shanghai reagent one factory, be mixed with 1% and 0.1% solution with acetone

Experimental animal: 80 of healthy guinea pigs, female, body weight 250～300g,

Test method: sensitization test (Buehler method);

Get 30 of Cavia porcelluss, female, after the laboratory nursing conformed in 3 days, be divided at random 3 groups, at the 0th, 7,14 days, use respectively the syringe with the gavage syringe needle, inject gel 1g, carbomer gel and positive group 1%2,4-dinitrochlorobenzene 0.2ml for the Cavia porcellus vagina and give once to induce, 1,24 hours, observe 3 groups of whole bodies and pudendum anaphylaxis situation.The 28th day, give experimental group booster dose 0.5g, repeat process of the test last time.Then in 24,48 hours, observe Cavia porcellus systemic anaphylaxis situation, put to death subsequently animal, vertical face cuts vagina, with after normal saline flushing, observes the vaginal mucosa anaphylaxis.By the standards of grading scoring, calculate average anaphylaxis score value and sensitization rate (anaphylaxis number of animals/all animals number * 100%).

Sensitivity test is within observing time, and gel treated animal vagina is without symptoms such as hyperemia, edema.The sensitization rate is 0%.Show gel to the Cavia porcellus vagina without sensitization, also have no the serious systemic anaphylaxis such as asthma, astasia or shock.

Result of the test is referring to table 8:

Table 8 local anaphylaxis result of the test

Annotate: sensitization rate 0-8% is without sensitization--weak sensitization

9-28% is slight sensitization

29-64 is moderate sensitization

65-80 is strong sensitization

81-100 is extremely strong sensitization

Testing result: during sensitivity test, gel treated animal vagina is without symptoms of allergic such as erythema or edema, and the sensitization rate is 0%, show gel to the Cavia porcellus vagina without sensitization, also have no the serious systemic anaphylaxis such as asthma, astasia or shock.

Conclusion: gel to vaginal mucosa without sensitization.

Claims (1)

1. a vaginal pH buffering antibacterial gel, is characterized in that comprising following component, by weight percentage:

Polycarbophil 0.8%-2.2%,

Carbomer 0.25%-0.5%,

Disodiumedetate 0.01%-0.03%,

Chitosan 1%-1.5%,

Glycerol 8%-12%,

Triethanolamine 0.31%-0.55%,

Methyl parahydroxybenzoate 0.25%-0.5%,

The deionized water surplus;

Described chitosan is water-soluble chitosan;

The preparation method of described vaginal pH buffering antibacterial gel, comprise the steps:

(1) by proportioning, take Polycarbophil and carbomer, add in the glycerol taken by proportioning, dispersed with stirring to pasty state obtains the glycerol pasty liquid;

(2) by proportioning, take chitosan, add deionized water, disodiumedetate, methyl parahydroxybenzoate, stir and make each components dissolved, obtain chitosan solution;

(3) chitosan solution is added in the glycerol pasty liquid, stir, with triethanolamine solution, its pH is adjusted to 3.8-4.4, obtain the gel of Polycarbophil and chitosan;

(4) stop stirring discharging;

(5) fill;

(6) aseptic process.