CN1470250A

CN1470250A - External-use disinfecting medicinal preparation for women

Info

Publication number: CN1470250A
Application number: CNA021335192A
Authority: CN
Inventors: 陈秀枢
Original assignee: Individual
Current assignee: Individual
Priority date: 2002-07-23
Filing date: 2002-07-23
Publication date: 2004-01-28
Anticipated expiration: 2022-07-23
Also published as: CN1203868C

Abstract

The invention is a female external disinfectant medicament. The components contain the following mian raw materials according to weight percent, and the raw materials are prepared into medicament: hydroxybenzoate ester 2-40%, mandelic acid 3-50%, lacidophihin 10-55% and oligose 8-50%. It is a new compound disinfectant medicament, its antibacterial effect mainly inhibiting the activity of the inner aspiratory enzyme of microbe cell and the electronic transfer enzyme system, and has the effect of destroying the permeation of microbe cell film, its antibacterial character: it has strong action on mildew and yeast mushroom. The mandelic acid has very strong activity of killing the protozoons like trichomonad and toxoplasma. The oligose is a indigestible sugar without any poisonous side effect on human body. The lacidophihin and oligose as micro-ecological regulator has remarkale "the effect of resting and benefiting".

Description

External-use disinfecting medicinal preparation for women

Technical field

The present invention relates to the pharmaceuticals technical field, specifically external-use disinfecting medicinal preparation for women.

Background technology

Vaginitis is the frequently-occurring disease of gynecological, from the classification of nosetiology angle, can be divided into colpitis mycotica, trichomonal vaginitis, bacterial vaginosis (bacterial vaginosis, BV; Be called nonspecific vaginitis in the past, non-specific vaginitis, NSV), senile vaginitis and gonorrhea, syphilis etc., though wherein preceding four class vaginitiss do not have gonorrhea, syphilis so serious on the state of an illness, but sickness rate is very high, the course of disease is long, and being easy to recurrence, also can the trafficability characteristic behavior propagating simultaneously, is to have a strong impact on the able-bodied commonly encountered diseases of numerous women.

Colpitis mycotica, trichomonal vaginitis, bacterial vaginosis and senile vaginitis are four kinds of commonly encountered diseases, and its pathogenetic common inducement is: the decline of vagina local immunity power, micro-ecological bacterial group imbalance, heavy dose or the treatment of prolonged application extensive pedigree antibiotic, use " system kills type " disinfectant, bad hygienic habit irrelevantly and factor such as spread through sex intercourse; On nosetiology, mycotic and trichomonal vaginitis have specific pathogen, and bacterial vaginosis and senile vaginitis mostly are the mixed infection of endogenous obligate anaerobe and facultative anaerobe, promptly, be that vagina often occupies due to the unusual breedings of a certain class in the flora or number class conditioned pathogens, as gardnerella vaginalis (modal conditioned pathogen), mycoplasma, golden Portugal bacterium, escherichia coli etc.; Aspect organic factor, young and middle-aged married women is in premenstrua and trimester of pregnancy, because the vagina estrogen level increases, make the interior glycogen levels of vagina epithelium increase, bring out colpitis mycotica and bacterial vaginosis easily, women after senile vaginitis then is mainly in menopause, because women's ovarian function of this age bracket is degenerated, body inner estrogen level reduces, the partial pH rising of vagina (pH5.8～6.8), thereby the helpfulness flora in the microecology in vaginas flora reduces, the self purification of vagina goes down, and is referred to as atrophic vaginitis again.Therefore, whether closely related factor such as situation of intravaginal estrogen level, glycogen content, pH value and micro-ecological bacterial clump and above-mentioned all kinds of colpitic morbidity be.In addition, above-mentioned four kinds of vaginitiss all have the characteristics of outbreak repeatedly clinically, and, the patient of significant proportion does not have conscious malaise symptoms, but its clinical consequences is quite serious, especially repeatedly outbreak or chronic bacterial vaginosis, very easily concurrent cervicitis, fallopian tube and ovary infection, pelvic inflammatory disease etc. also are the common causes that the women loses fertility.

In sum, vaginitis is to have a strong impact on able-bodied commonly encountered diseases of women and frequently-occurring disease.Because China is populous, and cultural quality is relative with hygienic habit backward, and the sexual behaviour knowledge of Gynecological health and health is relatively deficienter, the influence of traditional culture and constraint in addition, make a large amount of patients in time not obtain medical treatment, actual diseased person's prescription on individual diagnosis rate less than 20～30%.Simultaneously, shortage system, macroscopic microecological balance idea in the guidance of prevention and treatment, application antibiotics blindly and " system is type extremely " disinfectant, consequently vicious cycle that " rises one after another ".In recent years, though numerous scholars and hygiene department have recognized the severe situation of China's abuse of antibiotics, still, solve this phenomenon and need time and a large amount of popular science propaganda education.

At present, domestic prevention of having developed reaches over one hundred kind more than with all kinds of colpitic preparations of treatment, also the reaching of market circulation tens of kinds (wherein not comprising the various conventional antibiotics of using).On the route of administration of product, can be divided into general medication and local application's preparation; The accurate word of medicine is arranged, defend the accurate word that disappears, defend and make up word and the strong word of medicine etc. from the attribute of preparation; On the purposes of product, existing single sick preparation of planting (as the miconazole of antifungal etc.), the preparation (as metronidazole, tinidazole, JIEERYIN etc.) for the treatment of infusorian and bacterial vaginosis is simultaneously also arranged; From the prescription composition of preparation, single composition is arranged, compound preparation is also arranged, wherein mainly be divided into: antifungal drug is (as imidazoles, the polyenoid class), anti-bacterial drug is (as beta-lactam, aminoglycoside, macrolide, quinolones etc.), Chinese medicine is (as Radix Sophorae Flavescentis, Fructus Cnidii, garlicin, Rhizoma Coptidis, Radix Et Rhizoma Rhei, Cortex Pseudolaricis, the Fructus Kochiae, dried Alumen, tens of kinds of Herba Houttuyniae etc.), quaternary ammonium salt surface active agent, acetic acid, propanoic acid, salicylic acid, boric acid, policresulen (policresulen), povidone iodine (providone-iodine) and contain lactobacillus or the compound disinfecting medicament of lactein; On the preparation form of local application, can be divided into suppository, washing liquid, effervescent tablet, capsule, powder, cream, spray etc.

Because vaginitis is the global women's of puzzlement common disease, both just in the highly developed like this country of the U.S., vaginitis is still one of 25 kinds of commonly encountered diseases.Therefore, are one of important topics of medical circle to all kinds of colpitic effective controls.In present afloat all kinds of control agent, metronidazole or tinidazole are the trichomonal vaginitis of generally acknowledging and effective therapeutic agent of bacterial vaginosis, and still, their side effect also receives publicity day by day.Generally speaking, one time the user has 10～20% people to occur feeling sick and parageusia approximately, take for a long time and very easily cause colpitis mycotica and superinfection, wherein, when administration 2 days and 7 days, the concurrent colpitis mycotica of 6～8% and 26% patient is arranged respectively, and nervous system is caused damage, in the part or systemic treatment in pregnancy period, also serious consequences such as habitual abortion, stillborn fetus can appear.Imidazoles (as ketoconazole, econazole, fluconazol, clotrimazole etc.), polyenoid class (as amphotericin B, nystatin etc.) are the active drugs for the treatment of colpitis mycotica at present, but its toxic and side effects and treatment back high relapse rate are also generally acknowledged.

Summary of the invention

The purpose of this invention is to provide a kind of selective antibiotic with microecology and antibacterials and act as basic foundation, the common vaginitis that mycete, infusorian, vaginal flora disorder etc. are brought out has the external-use disinfecting medicinal preparation for women of preventive and therapeutic effect.

The present invention is in conjunction with domestic and international relevant progress, the experimentation and the demonstration of system have been carried out in aspects such as inside and outside bactericidal effect, toxicological safety, stability of formulation, production technology and quality standard at product attribute and functional localization, pathogenic microbes, drawn the present invention, concrete technical scheme is:

Contain following weight percentages in the key component, and be prepared into medicament: hydroxybutyric acid ester 2～40%, mandelic acid 3～50%, lactein 10～55%, oligosaccharide 8～50%.

Described medicament is the above a dosage form of any pharmaceutics, can be spray, washing liquid and effervescent tablet.

When making tablet, also contain following percentage by weight adjuvant in the component: boric acid 50～85%, sodium bicarbonate 10～40%, magnesium stearate 0.5～8% excipient.

The present invention is as the novel disinfectant of a compound type, antibiotic property composition p-Hydroxybenzoate in the Main Ingredients and Appearance, be through being widely used as the material of food preservative decades, prove its no obvious toxic-side effects, its antibacterial action mainly is the activity that suppresses microbial cell internal respiration enzyme and electron transport enzyme system, and the effect of destroy microorganisms membrane permeability arranged, suppress and the effect of killing certain micro-organisms thereby reach, its antimicrobial spectrum characteristics are strong to mycete and yeast-like fungi effect, and it is relative relatively poor, even invalid to the effect of bacillus acidophilus and Anaerobic Bacteria.Mandelic acid system in the prescription is by the natural product that extracts purification in the rosaceous plant leaf of Fructus Persicae, have very strong protozoacide activity such as infusorian, toxoplasma extremely, the effect of lactein is systematically discussed in preamble, and oligosaccharide FOS is the bacillus bifidus multiplicaiton factor of generally acknowledging in the world, it can reach 10～100 times height to the proliferate efficiency of endogenous bacillus bifidus, be to human body indigestion saccharide without any side effects, lactein and oligosaccharide (oligosaccharide) have significantly " supporting the benefit effect " as microecologic regulator.

So, in prevention and all kinds of colpitic methods of treatment and measure, combine with the microecological environment of safeguarding vaginal health with " selective antibiotic ", meet current and future science developing direction, its science also is well grounded with advance.

The mechanism of action of main antibacterials of table 4. and the true product of the present invention

The mechanism of action of this product of effect of main antibacterials commonly used

Change the thin plant interference cell of thin influence influence influence albumen influence thin biological antagonist bifid because of

The synthetic born of the same parents' metabolism jizi for making dumplings of the synthetic matter of the penetrating nucleic acid syncytial virus of after birth internal respiration insects wall

Property becomes the enzyme agent

To the hydroxyl β-sharp good fortune sulfonamides of Nei many Acarasiales of acyl Aminoglycoside almond

Flat (TMP) acid of the plain class class of benzoic acid lactein oligosaccharide amine

Ester

(also

Macrolide quinoline promise ethamine fourth changes thin vancomycin imidazoles

Class ketone alcohol after birth knot

Structure)

To amino cycloserine polyenoid class Tetracyclines

Salicylic acid

Pyrazine acyl bacitracin chloromycetin

Amine

The ground acid of furan west

The in-vitro antibacterial of medicament of the present invention (vagina effervescence) and infusorian effect extremely

1. materials and methods

Tried bacterium (worm) strain: Candida albicans ATCC 10231, the golden bacterium ATCC of Portugal 25923, escherichia coli ATCC 25922 and bacillus acidophilus ATCC 314, with the 3rd～8 generation culture for being tried bacterium; Trichomonal vaginitis clinical strain (3 strain) for after the rejuvenation the 3rd generation culture; Various objectives bacterium and worm strain increase bacterium through liquid meat soup, cultivate suspension for being tried bacterium (worm) strain with the worm strain of logarithmic (log) phase bacteria suspension and 12h; Culture medium method is as described above selected for use.It dissolves that (concentration is: 50 are dissolved in 100ml to effervescent tablet with appropriate solvent and cosolvent, be 25mg/ml), pH is adjusted to 2.5 ± 0.5, and be mixed with the test medicinal liquid, and this medicinal liquid is made four dilution factors of 1,2,4,6 times of dilution, and effect is tried 1,2,4,5 hours four times of bacterium (worm) strain respectively, after removing medicine, tried bacterium and be inoculated in each purpose bacterium test agar flat board, cultivated 48～72h, observed result for 35 ℃; Tried the worm strain and directly used the ultramicroscopic observation mobility, granulating and polypide ulceration rate.Establish positive control (no medicine group) and negative control (blank culture medium) respectively.

2. result: see the following form.

Qualitative sterilization (worm) result of the test of medicament of the present invention (washing liquid)

Tried bacterium (1.5 * 10 ⁶ Cfu/ml), the worm strain (5 * 10 ⁴ Individual/ml) with action time (h)Concentration/contrast Candida albicans staphylococcus aureus escherichia coli bacillus acidophilus's infusorian clinical strain (dilution factor) ATCC 10231 ATCC 25923 ATCC 25922 ATCC314

1 2 4 5 （ h ） 1 2 4 5 （ h ） 1 2 4 5 （ h ） 1 2 4 5 （ h ） 1 2 4 5 （ h ） ×1 100％×2 100％×4 ＋＋--100％×6 ＋＋＋-＋＋＋-＋＋--＋＋＋＋ 100％：48-72h“”“”，“＋”“-”； Worm strain mortality rate is represented with %.Liquid stock solution is pressed embodiment 2 preparations 3. interpretations of result

This dosage form medicinal liquid is tried pathogen in the stock solution of experimental concentration, 2 times of dilutions and 4 times of diluted concentrations to 3 strains and is all possessed inhibition or dissipation effect fully, and trichomonacide is had 100% killing action.

This dosage form medicinal liquid has the bacillus acidophilus in stock solution and 2 times of diluted concentrations and to suppress fully or killing action, but only presents bacteriostatic activity when 4 times and 6 times of diluted concentrations.Explanation is weaker than pathogen to the antibacterial action of lactobacillus.

The microorganism killing test of medicament of the present invention

Medicament stock solution of the present invention was to escherichia coli effect 10 minutes, and average kill ratio is 100%, and to staphylococcus aureus effect 15 minutes, average kill ratio was 99.98%; To Candida albicans effect 15 minutes, average kill ratio was 99.99%.Medicament was deposited in 37 ℃ of incubators after 90 days, and to escherichia coli effect 10 minutes, average kill ratio was 99.99.Meet GB15981-1995 standard (killing rate 〉=99.9%) regulation.

Medicament stock solution of the present invention acts on 15 minutes to the bacillus acidophilus, and average kill ratio is 61.50%; To bacillus bifidus effect 15 minutes, average kill ratio was 65.80%, and the result that examines does not meet GB15981-1995 standard (killing rate 〉=99.9%) regulation.

The above results illustrates that medicinal liquid of the present invention has the selectively killing effect to microorganism.Pathogenic bacterium (staphylococcus aureus, Candida albicans etc.) had significant killing action, and the killing rate of beneficial bacteria in the human body (bacillus acidophilus, bacillus bifidus) is not met GB15981-1995 standard (killing rate 〉=99.9%) regulation, promptly the killing action to beneficial bacteria is invalid.

The acute oral toxicity experiment of medicament of the present invention (spray)

One, material and animal

1, tried thing: washing liquid of the present invention, sample are light brown liquid.

2, animal: Kunming kind white mice, body weight 18-21.5g is provided (the animal quality certification number: No. the 9712nd, the real moving card in Yunnan) by Chinese Academy of Sciences's Kunming zooscopy.

Two, method

1. test basis: " disinfection technology standard " third edition first fascicle 3.4 acute orals poison test.

2. test method:

Mensuration, dosage is established 20000mg/kg, gets 20 animals, and male and female half and half are irritated the preceding animal of stomach

Fasting 12 hours, one time per os is irritated stomach, observes record animal poisoning symptom continuously 14 days

And death condition.

Three, experimental result:

Animal subject is at viewing duration, and not seeing has obvious poisoning symptom, does not see death.

Four, conclusion

Under this experiment condition, tried thing (spray of the present invention) animal subject white mice per os toxicity test is pressed anxious toxicity LD ₅₀The dosage grade scale is judged to be actual nontoxic.

Specific embodiments

Embodiment 1:

Get percentage by weight raw material hydroxybutyric acid ester 8%, mandelic acid 36%, lactein 30%, it is standby that oligosaccharide 26% is hybridly prepared into major ingredient; Reuse boric acid 78%, sodium bicarbonate 20%, magnesium stearate 2% is hybridly prepared into adjuvant; With the major ingredient for preparing and adjuvant by 4: 1 mixed after, make the vagina effervescence tablet with existing method.

Embodiment 2:

Get percentage by weight raw material hydroxybutyric acid ester 25%, mandelic acid 18%, lactein 23%, it is standby that oligosaccharide 34% is hybridly prepared into major ingredient; Water, OP, propylene glycol etc. are prepared into non-ionic surface active agent according to a conventional method as solvent, and the dissolving major ingredient is mixed with the external spraying agent that concentration is 30mg/ml.

Embodiment 3:

Get percentage by weight raw material hydroxybutyric acid ester 21%, mandelic acid 19%, lactein 26%, it is standby that oligosaccharide 34% is hybridly prepared into major ingredient; Water, OP, propylene glycol etc. are prepared into non-ionic surface active agent according to a conventional method as solvent, and the dissolving major ingredient is mixed with the external wash liquid that concentration is 25mg/ml.

Claims

1, a kind of external-use disinfecting medicinal preparation for women is characterized in that containing in the component main material of following weight percentage ratio, and is prepared into medicament: hydroxybutyric acid ester 2～40%, mandelic acid 3～50%, lactein 10～55%, oligosaccharide 8～50%.

2, external-use disinfecting medicinal preparation for women according to claim 1 is characterized in that described medicament is the above a dosage form of any pharmaceutics.

3, external-use disinfecting medicinal preparation for women according to claim 1 also contains following percentage by weight adjuvant: boric acid 50～85%, sodium bicarbonate 10～40%, magnesium stearate 0.5～8% excipient in the component when it is characterized in that making tablet.