CN101721395A - Water soluble gel containing xylitol and application thereof in medicine for treating cervical erosion - Google Patents

Abstract

The invention relates to water soluble gel containing xylitol and carrying out internal administration through the local vagina and an application thereof in preventing and treating a uterine cervix disease named as cervical erosion.

Description

The water-soluable gel and the purposes on treatment cervical erosion medicine thereof that contain xylitol

Technical field

The present invention relates to a kind of medicine of the women's of treatment cervicitis, specifically is the water-soluable gel that contains xylitol, comprises the collocation method and the application of this medicine.

Background technology

The knowledge of xylitol

Xylitol is a kind of sugar alcohol of pentitol type, and it has 5 carbon atoms and 5 hydroxyls.Xylitol belongs to polyhydric alcohol, and polyhydric alcohol is not a sugar on the stricti jurise.But they are relevant with sugar on biochemistry, because produced by sugar, and can be converted into sugar.In addition, some chemical handbook are defined as the carbohydrate of crystallization, sweet taste with sugar, and it is the category that covers xylitol.

The mankind have just known xylitol the nineties from 19th-century at least organic chemistry.Before more than 100 years, German and French researcher has at first chemically been produced xylitol.During nineteen thirties, finally determined the characteristic of xylitol and it has been purified.Although from chemical aspect, xylitol has quite long history, and it is considered to a kind of in several sweet carbohydrates for a long time.But during the Second World War owing to the shortage of sugar, a lot of countries increase xylitol interest.Studied its noninsulin dependent performance up to researcher, its biological characteristics just obtains understanding, up to nineteen seventies, a lot of countries are just with the sweeting agents of xylitol as diabetics, with parenteral alimentation promptly by blood vessel directly give with nutrition or treatment islets of langerhans disposition go into a coma relevant.Just begin in odontology, to use xylitol during nineteen seventies.The chewing gum of xylitol has at first appearred containing in Finland in 1975, and it is used to control dental caries.

Internal and international authority estimates its toxicity, thinks that its toxicity is so low, to such an extent as to for acceptable daily intaking amount without any restriction.Referring to translate (English) sieve R.C. " 796 pages of xylitol of pharmaceutic adjuvant handbook (original work the 4th edition) that Chemical Industry Press publishes by Zheng Jun democracy.

The knowledge of cervical erosion

Cervical erosion is the modal a kind of pathological changes of gynecological clinic, show as that cervix uteri collar extension circumferential surface takes on a red color and coarse, smooth different with the pale red of normal cervix, portio vaginalis, rotten to the corn district is not all to be true erosion, because of its surface is covered by neck tube inner membrance columnar epithelium, what seen is neck tube internal film tissue because the neck tube intimal epithelium has only the monolayer cylindrical cell, therefore between in the matter redness of blood vessel just show.

Cervical erosion can be divided into two big classes by its mechanism.

(1) physiological erosion

These so-called erosions are relevant with estrogenic variation in fact.Owing to be subjected to the parent effect of estrogen, neck tube inner membrance columnar epithelium is displaced to beyond the collar extension, after the birth when neonate, neonate body inner estrogen reduces gradually, the swelling of neck tube mucosa is gone down, is dwindled, and the displacement inner membrance is returned in the neck tube, and squama column intersection also enters in the neck tube thereupon like this.Have the secretion estrogen function to the adolescence ovary, neck tube inner membrance lower bound begins again to move down, and part adolescence women neck tube inner membrance can be displaced to outside the collar extension again.The gestation first tire neck tube inner membrance columnar epithelium hypertrophy, a matter congestion and edema, membrane volume increases in the neck tube, causes the neck tube inner membrance and prolapses again and be displaced to outside the cervix uteri collar extension, has so just formed so-called physiological erosion.Because ovary produces estrogen decrease so that disappears, the squamous epithelial cancer of atrophy of neck tube inner membrance and collar extension ectocervical is retracted in the neck tube together after menopause.These all belong to the physiological change.Therefore, at all ages and classes the physiological erosion that the displacement of cervical canal inner membrance causes can appear.The also corresponding occurrence positions of the transfer of cervix uteri columnar epithelium and squamous epithelial cancer intersection moves like this.

(2) true erosion

The period of duration women is more common in [pathology] this erosion.Because the cervix uteri vagina strips off because of inflammation or damage near the squamous epithelial cancer of collar extension, belongs to true erosion.Covered by the columnar epithelium of neck tube inner membrance to outgrowth but true erosion is very fast, the surface takes on a red color.This claims primary healing, also claims the gland erosion.Later this columnar epithelium squamaization is gradually substituted by squamous epithelial cancer, is called secondary healing.The squamous epithelial cancer of repairing can be from rotten to the corn edge, former squamous epithelial cancer that pre-exists or residual squamous epithelial cancer regeneration, but more be to form by squama by columnar epithelial cell.When the surface of this cervical tissue was covered by stratified squamous epithelium again, the mucomembranous surface of ectocervical returned to original smooth and be pale red again.This new life's or the squamous epithelial cancer of change giving birth to participates in the cervical mucosa squamous and the columnar epithelium connecting band has promptly been formed transitional zone or zone of transformation, the predilection site that is regarded as tumor owing to herein squamous or columnar epithelium active growth.Except transitional zone, dispersive squama island can also be present in the neck tube columnar epithelium.

[clinical symptoms] cervical erosion is the modal pathological changes that occurs together of cervix uteri chronic inflammation, and its symptom can have leucorrhoea grow in quantity with the cervix uteri chronic inflammation, is sanguinous leukorrhea sometimes, and waist and sacrum pain and pelvic cavity portion bearing down can be arranged during serious symptom.

Visible cervix uteri had erosion in various degree when [diagnosis] checked.Big I according to rotten to the corn area is divided into three degree; Refer to that slightly rotten to the corn face is less than 1/3 of whole cervix uteri area; Moderate refers to that rotten to the corn face accounts for the 1/3-2/3 of whole cervix uteri area; Severe refers to that rotten to the corn face accounts for more than 2/3 of whole cervix uteri area.Depth degree according to rotten to the corn face can be divided into simple type, granular pattern and emulsus type 3 types.Should represent the rotten to the corn area and the depth simultaneously during diagnosis cervical erosion.Cervical erosion and Cervical intraepithelial neoplasia change or early cervical carcinoma are from being difficult to differentiate that the palpus routine be done the cervical scraping smear cytolgical examination, does biopsy in case of necessity to clarify a diagnosis in appearance.

[control] when avoiding giving a birth or apparatus damage cervix uteri, finds that laceration of cervix should in time sew up puerperal; Gynecologial examination regularly gives active treatment when finding the cervix uteri inflammation.

Treatment cervical erosion can adopt naturopathy, Drug therapy and operative treatment based on topical therapeutic, and the most commonly used with naturopathy.

1, naturopathy is with various physical methods cervical erosion face epithelium to be destroyed, and makes it downright bad, comes off, and the squamous epithelial cancer by new life is covered later on, generally needs 3-4 week, and the dark person of pathological changes needs 6-8 week, and cervix uteri transfers to smooth.Physiotherapy at present commonly used is electric rubbing hot medicated compress, is frozen gradually recently, Therapeutic Method such as laser, infrared ray, microwave substitute.Various physiotherapys are similar, and treatment time is selected in the clean back of menstruation 3-7 and carries out in day.Various edeitis person taboos are arranged.There is vaginal secretions to increase after the treatment, a large amount of water sample discharge opeings are very arranged.Postoperative 1-2 can have a little vaginal hemorrhage during the week decrustation.In wound surface not (postoperative 4-8 week) taboo bath in a tub, sexual intercourse and vaginadouche etc. between healing stage fully as yet.Postoperative is wanted periodic review, observes the wound healing situation and has or not neck tube narrow.

2, Drug therapy can be divided into two kinds of part and systemic administrations.Topical medications is used for the less and more shallow case of inflammatory infiltration of rotten to the corn area.Common in the past local application of silver nitrate or chromic acid corrosion, now few using.Antibiotic suppository has certain curative effect.Whole body therapeutic is applicable to endocervicitis, its cervical canal smooth in appearance, the person that has the purulent secretion in the neck tube.Endocervicitis local application weak curative effect, palpus row whole body therapeutic is got cervical secretions and can be done to cultivate and medicament sensitivity test, so that select corresponding anti-infectives for use.

3, operative treatment extensively and especially deeply particularly adds up neck tube when dark when cervical erosion, can consider to do conization.Referring to edit " cervix diseases " that the People's Health Publisher publishes by Shi Yifu

Summary of the invention

With respect to electricity press, physiotherapys such as freezing, laser, microwave and LEEP cutter, treatment cervical erosion is to destroy erosion to organize cervix uteri oral pillar columnar epithelium, what grow then organizes squamous epithelial cancer; Organize cervix uteri oral pillar columnar epithelium and partial smearing Albothyl (policresulen) concentrated solution, silver nitrate or chromic acid also are the chemical attack erosions, what grow then organizes squamous epithelial cancer.

The purpose of this invention is to provide a kind of new product that is different from physical damage therapy and chemical attack therapy for treating cervical erosion, be ready to accept, do not have new wound, do not have misery in treatment cervicitis especially patients of cervical ruin, and use more conveniently, expense still less.

Another object of the present invention is can be used as naturopathy auxiliary, adopt that electricity is pressed, after freezing, laser, microwave and the treatment of LEEP cutter, in order to promote to repair, can adopt the local use of product of the present invention, can make wound healing faster, make the healing stage in average 4-8 week behind the naturopathy be reduced to 2-4 week.And the sense of discomfort behind the naturopathy is obviously alleviated.

The inventor turns to xylitol with sight, is based on following document and personal experiment.Translated by Zheng Jun democracy, " 796 pages of xylitol chapters and sections of pharmaceutic adjuvant handbook (original work the 4th edition), mention xylitol has certain special antibacterial and bactericidal effect to (English) sieve R.C. that Chemical Industry Press publishes, especially to common putrefactive microorganisms.The disclosed experiment of Chinese invention patent (application number 200810089039.X) that the inventor submits to shows that xylitol sodium chloride liquid (5% xylitol, 0.9% sodium chloride) flushing more can reduce pollution than simple normal saline flushing, promotes wound healing.The Chinese invention patent (application number 200810084624.0) that the inventor submits to is mentioned the purposes of xylitol on cervical erosion, but mentions big, many, the trivial operations of waste of xylitol amount that irrigation needs in the literary composition.For cervical erosion, it is generally acknowledged that medically the physiological erosion need not treat, and Symptomatic true erosion should be treated and with examining check.The inventor thinks that the true erosion of cervical erosion has symptom to be because be associated with in various degree cervix uteri inflammation, and under the situation of or transfusion unsatisfactory curative effect oral at antibiotic, local application is comparatively ideal mode.Xylitol can directly be utilized by human body cell, and antibacterial can not decompose and utilize xylitol, and this point is different from glucose.Xylitol is executed and is spread on the local rotten to the corn place of cervix uteri, can provide energy for human body cell, keeps the normal function of human body cell, can suppress the breeding of common microorganism again, antibacterial hungry to death.

The inventor is through consulting document and testing repeatedly, and the best carrier of determining to use xylitol is a water-soluable gel.This is because xylitol is water miscible, and water-soluable gel helps xylitol and discharges, and enters tissue; Water-soluable gel is easy to coating, no greasy feeling, and energy absorptive tissue transudate makes rotten to the corn slough drain by vagina, does not hinder Mucocutaneous normal function.The water-soluable gel substrate here is meant bio-adhesiveness or mucoadhesive carrier, specifically is carbomer, sodium polyacrylate, sodium alginate, hydroxypropyl cellulose, pectin, xyloglucan etc.According to the present invention, except bio-adhesiveness or mucoadhesive carrier, this medicament also can contain optional composition, as antiseptic and antibacterial, absorption enhancer, thickening agent, antioxidant, acidity regulator etc.Antiseptic and antibacterial can select that ethylparaben, methyl ester, propyl ester and butyl ester, benzoic acid, benzylalcohol, chloroethene are fixed for use, triclosan, Benzalkonii Chloridum etc.Absorption enhancer can be selected Oleum menthae for use.Acidity regulator can be selected triethanolamine, sodium bicarbonate, diluted sodium hydroxide solution for use when bio-adhesiveness or mucoadhesive carrier vector were carbomer, acidity regulator can be selected lactic acid for use when bio-adhesiveness or mucoadhesive carrier vector were sodium polyacrylate or hydroxypropyl cellulose, regulate pH value between 3.5～5.5, close with normal acid vagina environment.

The inventor has also determined gel is imposed on mashed available disposable female cysthus canal drug administration device in place of cervix uteri erosion of the oral mucosa or disposable woman vagina injector.

The inventor expects that at first xylitol is used for the treatment of and prevents cervical erosion, before the inventor proposes this viewpoint and implements, does not see any document or the patent report to this purposes of xylitol as yet.

The specific embodiment

Embodiment 1

Prescription is formed:

Xylitol 100g

Carbomer 4g

Ethylparaben 0.3g

Oleum menthae 1ml

Triethanolamine 0.4ml

Deionized water adds to 1000ml

Preparation process:

Precision takes by weighing carbomer 4g and was scattered in about 600ml pure water swelling 24 hours, adds triethanolamine again and transfers pH value to 4.0～5.0.Other is with an amount of warm dissolved in purified water ethylparaben 0.3g, Oleum menthae 1ml, xylitol 100g, and slowly adding is gone up in the liquid, adds deionized water to 1000ml, stirs evenly and promptly gets transparent xylitol carbomer gel I.

Embodiment 2

Prescription is formed:

Xylitol 50g

Carbomer 5g

Ethylparaben 0.3g

Oleum menthae 1ml

Sodium bicarbonate 0.5g

Deionized water adds to 1000ml

Preparation process:

Precision takes by weighing carbomer 5g and was scattered in about 600ml pure water swelling 24 hours, adds sodium bicarbonate again and transfers pH value to 4.0～5.0.Other is with an amount of warm dissolved in purified water ethylparaben 0.3g, Oleum menthae 1ml, xylitol 50g, and slowly adding is gone up in the liquid, adds deionized water to 1000ml, stirs evenly and promptly gets transparent xylitol carbomer gel II.

Embodiment 3

Prescription is formed:

Xylitol 50g

Cross-linked sodium polyacrylate 400 10g

Ethylparaben 0.3g

Oleum menthae 1ml

Deionized water adds to 1000g

Preparation process:

Get 60 ℃ of deionized water 600ml, cross-linked sodium polyacrylate 400 is spread on liquid level, place 24h, allow its swelling form gel.Other is with an amount of warm dissolved in purified water ethylparaben 0.3g, Oleum menthae 1ml, xylitol 50g, and slowly adding is gone up in the liquid, adds deionized water to 1000ml, stirs evenly and promptly gets transparent xylitol gel III

Embodiment 4

Prescription is formed:

Xylitol 50g

Sodium carboxymethyl cellulose 30g

Ethylparaben 0.3g

Oleum menthae 1ml

Deionized water adds to 1000g

Preparation process:

Get xylitol and mix, add appropriate amount of deionized water and stir to place, allow the abundant swelling of sodium carboxymethyl cellulose, stir evenly gel with sodium carboxymethyl cellulose.Other gets ethylparaben, Oleum menthae in an amount of hot deionized water, places, and is cooled to about 50 ℃, mixes stirring evenly with above-mentioned gel, adds water to capacity at last, stirs evenly and promptly gets transparent xylitol gel IV.

(annotate: Oleum menthae is nonessential.Adding Oleum menthae can increase refrigerant comfortable sensation after the medication, and for the big and dark patient of rotten to the corn face, Oleum menthae stimulates wound, and the initial stage is used the sensation that has pain, but does not influence healing time.)

Clinical effectiveness

For simple patients of cervical ruin, adopt the water-soluable gel part contain xylitol to propel, before sleeping every day once, general 6 to 8 times, clinical symptom disappearance, the cervix uteri epithelium restores fully and recovers.Patients of cervical ruin is gone ahead of the rest behind laser or the micro-wave therapeutic, propels the water-soluable gel that contains xylitol at wound surface, and the wound healing phase obviously shortens, and general two all left and right sides wound healings are compared the normal healing phase (all around to eight weeks) behind laser or the micro-wave therapeutic.Be to use some clinical effectiveness examples that the present invention contains the xylitol water-soluable gel below:

Example one,

Dong so-and-so, women, date of birth in December, 1975.On March 4th, 2008 is because of lower abdomen dull pain, leucorrhoea grow in quantity, and midcycle increases the weight of, and goes to a doctor.Physics (laser) treatment cervical erosion was once done in patient's private prosecution in the year before.

Ultrasound diagnosis is no abnormal.BV(-)。Colposcopy: vulvovaginal (-), cervix uteri moderate erosion (rotten to the corn face account for full cervix uteri area 1/3～2/3)

So allow the patient directly use 3 gram xylitol carbomer gel I in cervix uteri in night once a day, continuous six days.Checked January afterwards, and the demonstration cervix uteri is restored fully, and the patient also feels well, do not have uncomfortable.

Example two,

Suddenly so-and-so, women, in May, 1980 date of birth.On March 11st, 2008 went to a doctor because of, sexual anhedonia hemorrhage with bed.Patient's last menstrual period March 1, ultrasound diagnosis is no abnormal, vulvovaginal (-), liquid base C (-) severe cervical erosion (rotten to the corn face accounts for more than 2/3 of full cervix uteri area)

So allow the patient directly use 3 gram xylitol carbomer gel II in cervix uteri in night once a day, continuous ten days.Checked January afterwards, and the demonstration cervix uteri is restored fully, and the patient also feels well, do not have uncomfortable.

Example three,

Bai, women, in March, 1981 date of birth.On March 11st, 2008 went to a doctor because of flank pain, sexual anhedonia, leucorrhea more.Patient's last menstrual period February 29, ultrasound diagnosis is no abnormal, vulvovaginal (-), and BV (-), liquid base C (-) points out parillomarvirus infections, severe cervical erosion (rotten to the corn face accounts for more than 2/3 of full cervix uteri area)

So the rotten to the corn place of laser calcination enjoins to allow the patient directly use 3 gram xylitol carbomer gel II in cervix uteri in night once a day, continuous ten days more in advance.Stop using menstrual period.Checked January afterwards, and the demonstration cervix uteri is restored fully, and the patient also feels well, do not have uncomfortable.Consider that human papillomavirus easily recurs, advise patient's periodic review.

Example four,

Liu so-and-so, women, in January, 1970 date of birth.On March 18th, 2008 went to a doctor because of pudendum Pruritus, flank pain, leucorrhea more.Patient's last menstrual period March 3, ultrasound diagnosis is no abnormal, the vaginal secretions smear is seen typical spore and pseudohypha, ammonia experiment (+), the prompting vulvovaginal candida infects, and other sees that cervix uteri moderate erosion (rotten to the corn face account for full cervix uteri area 1/3～2/3) at first treats vulvovaginal candida, and Kai Niting (clotrimazole sheet) is used in intravaginal, one week relief patient directly uses 3 gram xylitol carbomer gel II in cervix uteri in night once a day, continuous eight days.Stop using menstrual period.Checked January afterwards, shows the vulvovaginal candida healing, and cervix uteri is restored fully, and it is good that the patient also feels.

Claims (7)

1. xylitol is used to make purposes on the restorative local intravaginal medicament of cervical mucous membrane abrasion epithelial tissue that the cervical erosion place takes place in preparation.

2. purposes as claimed in claim 1 is characterized in that, described local intravaginal medicament contains the xylitol of 1～30 weight %.

3. purposes as claimed in claim 1 is characterized in that, described local intravaginal medicament also contains one or more bio-adhesiveness or mucoadhesive carrier.

4. purposes as claimed in claim 3 is characterized in that, described bio-adhesiveness or mucoadhesive carrier are selected from carbomer, sodium polyacrylate, sodium alginate, hydroxypropyl cellulose, pectin or xyloglucan.

5. purposes as claimed in claim 1 is characterized in that, the form of described local intravaginal medicament is to contain 5～15 weight % xylitol and as the carbomer gel of bio-adhesiveness/mucoadhesive composition.

6. purposes as claimed in claim 1 is characterized in that the pH value of described local intravaginal medicament is between 3.5～5.5.

7. purposes as claimed in claim 1 is characterized in that, described local intravaginal medicament is suitable for delivering medicine to infection site by being furnished with the suitable intravaginal intubate of using means.