CN104771790A - Midwifery gel preparation method - Google Patents

Abstract

The present invention discloses a new midwifery gel preparation method, which is designed by referring bionics and comprises three parts such as a drawing mucilage, a gel skeleton, and gel microspheres. According to the present invention, the drawing mucilage refers a organism lubricating liquid, adopts sodium hyaluronate as a main component, is added with carbopol so as to increase skin affinity, and is added with hydroxyethyl cellulose so as to adjust viscosity; the whole formula is similar to the formula of the lubricating liquid in the human body, and the same viscosity, the same drawing ability and the same skin affinity are provided; the network skeleton gel provides strong compressibility and strong film-forming property for the system, such that about 30 kPa pressure is generated to squeeze the gel so as to form the flowing elastic viscous film with a thickness of about 0.24 [mu]m when the fetus enters the birth canal; and the system is added with 50-100 nm sodium alginate gel microspheres, such that the original interlayer sliding friction of the gel is changed into the rolling friction so as to reduce the sliding friction, effectively reduce the static friction, such that the residence time is reduced, the injury and the pain during parturient uterine contraction are reduced, and the delivery time is shortened.

Description

A kind of preparation method of practise midwifery gel

Technical field

The present invention relates to the preparation method of practise midwifery gel, belong to biochemical field of medicaments.

Background technology

The vaginal delivery of baby is a complicated process, woman produces medical research and proves, give a birth by three aspect factor decisions such as childbirth thing (fetus, amniotic membrane, Placenta Hominis), birth canal (being made up of bone parts and soft tissue pipeline) and childbirth power, woman produces medical research and shows, promote that the power of giving a birth is uterine contraction and gravity, and the power of suppression childbirth is the tension force of orifice of uterus and birth canal.

The childbirth of people baby is divided into 3 stages: opening phase, the phase of giving birth to and rear term.The normal labor persistent period average out to of primipara 12 hours, and the normal labor persistent period average out to 8 hours of multipara.Compared with primipara, the average childbirth persistent period shorter reason of multipara is that the tension force of birth canal reduces, because the soft tissue pipeline of multipara (inner soft tissue conduit (uterus section---cervical canal---soft tissue attachment tube (vagina and vulva))) is thinning through previous vaginal delivery.Therefore, the give a birth main theory of mechanics of relevant people is: the tension force of birth canal (open birth canal, stretch birth canal and make the thinning required power of birth canal) is considered to the power of important obstruction childbirth.

The misery of puerpera in spontaneous labor process is unmodifiable objective fact, due to puerpera give a birth time misery and fear, birth process is often made to be full of all multi-risk Systems, not only can cause huge injury to puerpera's health, also baby can be made several because difficult labour, anoxia and cause brain injury, even also can cause mother or baby's death, therefore, a lot of puerpera selects laparotomy ventrotomy when giving a birth, but because laparotomy ventrotomy exists certain risk, what be not only unfavorable for after parturient childbirth is multiple extensive, nor is beneficial to the growth of baby.

World Health Organization (WHO) (WHO) repeatedly writes articles and appeals to encourage spontaneous labor, reduce non-adaptive card Cesarean esction, the warning line of cesarean delivery rate controls below 15% by suggestion, WHO recent statistics in 2010 announce 2007 ?the Sampling Investigation Report of Asia nine state childbirth options in 2008, point out that Chinese cesarean delivery rate reaches 46.2%, Individual hospitals even reaches 68%, wherein reach 11% without Medical indication Cesarean esction ratio, become one of country that cesarean delivery rate is the highest in the world, the warning line of cesarean delivery rate is fixed on 15% by World Health Organization's suggestion, and China is far apart apart from this target.

Alleviate the misery of puerpera in spontaneous labor, be not only love, be more conducive to reduce the Cesarean esction without indication, be more conducive to preventing hazard event when giving a birth from occurring, such as puerpera's health excessively injures, baby's injury, even jeopardizes mother and baby's life.

In veterinary, the childbirth mechanical meaning of the frictional force between childbirth thing and birth canal is aware of many decades.Using lubricant to birth canal is standard method [2] in veterinary assisted birth to reduce friction, and for the commercially available acquisition of lubricant of this object.In animal childbirth, relatively large amounts of lubrication can be used.Can use the aqueous compositions of liquid thus, it is used as the amniotic fluid of lubricate or the substitute of allantoic fluid in useful animal.

One between the childbirth of animal and the childbirth of people is not both substantially: when people's term labor, the effect of amniotic fluid is with lubrication birth canal without significant correlation, and may increase caused frictional force on the contrary.Amniotic fluid (as hydrous matter) itself does not have significant lubricant effect in people.At present, in people, vaginal delivery major part is only carried out with head position, and wherein due to the blocking of head, the discharge of amniotic fluid is thought inessential in the progress of labor.Vernix caseosa (unique greasing substance of childbirth thing) major part no longer exists about expected date of confinement, and correct in a word only have very little effect.Therefore, amniotic fluid or amniotic fluid substitute is used not to be for reducing friction and making people's vaginal delivery be easy to enough suitable method to lubricate birth canal before the vaginal delivery of people or in its process.

The childbirth of puerpera is exactly the problem of frictional force in essence.Because uterine contraction is intermittent behavior, the process that therefore whole birth process is actually static friction---dynamic friction---between static friction constantly transforms mutually, we between idle period call: residence time (dwell time).Formula f=μ N(f according to frictional force in physics is birth process friction, and μ is coefficient of friction, the normal pressure of N suffered by birth process).Formula that is quiet in physics, kinetic force of friction is identical, and difference is coefficientoffrictionμ, and confficient of static friction is greater than the coefficient of kinetic friction in general.Therefore the continuous conversion of sound friction, also can allow product produce the continuous sensation of deepening of pain.

United States Patent (USP) 3,814,797 disclose moisture lubricating composition, it is based on (A) potassium metaphosphate, (B) alginic acid, carboxymethyl cellulose, carboxymethyl starch and salt thereof, and the sodium salt of (C) weak acid, such as sodium carbonate or sodium phosphate;

United States Patent (USP) 3,971,848 disclose the lubricant compositions for mucosa, and it contains the mixture of fucoidin and alginate, said composition can optionally mix with carboxymethyl cellulose, sodium polyacrylate, sodium polyphosphate potassium, poly(ethylene oxide) etc., and for making childbirth easy;

United States Patent (USP) 4,267,168 disclose a kind of liquid biocidal composition, and it can be used as abluent, surface disinfectant or vaginal lubricant.Said composition comprises lauryl diglycollic amide, propylene glycol, glycerol, poly-pectic acid sodium and silver ion;

JP46,024,256 disclose a kind of lubricant compositions, and it is made up of polyacrylate substantially, and can be used as promotion property uterine luminal fluid in veterinary;

JP45,000,153 and JP4,500,012 disclose a kind of in veterinary for promoting the lubrication chaste tree compositions of giving a birth, it comprises the salt of alginic acid or ester and arabic gum;

JP46,034,991 disclose and a kind ofly comprise the lubricant compositions that polycyclic oxygen second in a liquid burns powder, described liquid by concentration be the organic solvent of >80%, hydroxypropyl cellulose, sodium sulfate and detergent form.In kind medical science, said composition can carry out the taking-up using to contribute to fetus after dilution;

PCT/EP03/0054 to disclose on physiology the purposes of organic substance without a doubt for the preparation of the compositions of the alkali metal salt not containing Metaphosphoric acid, and described compositions is used as lubricant in the vaginal delivery of women.To be referred on suitable physiology many examples of organic substance without a doubt.The target of this invention is, by power that is that recognize in the medical science that makes with lubricator to reduce in people to give a birth, important, that hinder childbirth, and the frictional force namely between childbirth thing and birth canal;

International publication W02006/050951(China Patent Publication No. CN101087587A) disclose a kind of people of making and give a birth and be easy to have the gel combination of good adhesion character and lubrication, containing Carbomer polyacrylic acid, water-soluble cellulose class thickening agent, wetting agent and water etc.;

China Patent Publication No. CN102228720A discloses a kind of childbirth with lubricator, is made up of water, sodium chloride, propylene glycol, glycerol, natrosol and xanthan gum.

But, unfortunately, on the one hand, flow out from birth canal because puerpera has the physiological fluid such as amniotic fluid, blood in the progress of labor, often weaken the lubricant effect of lubricant compositions, although the soft tissue pipeline of puerpera is convenient to clean for water miscible lubricant, but for natural, there is the better affine of the composition of greasy property, physiological fluid can not be made to weaken its lubricant effect, and therefore, the lubricant effect of the compositions that technique scheme provides is not good enough; And on the other hand, the feelings of reality are heavy is, because puerpera and fetus immune level is in the progress of labor very low, birth canal can be hemorrhage and often carry out perineal incision art, very likely increases the chance of local and systemic infection in birth process, therefore, making practise midwifery lubricant not only have efficient lubricant effect, not only safety but also have anti-microbial property, be very important, but antibiotics chemical substance uses at practise midwifery lubricant, often unfavorable to baby, or even danger close.

Amniotic fluid due to puerpera mainly contains normal saline and minute quantity mucin is formed, and its viscosity, skin-friendly are nowhere near, in whole birth process, also effectively cannot reduce frictional force, and can be absorbed by birth canal very soon.Therefore can think that the frictional force of spontaneous labor process meets " solid friction " model.Add practise midwifery gel again and there are 3 kinds of models later simultaneously: form lubricating film under stress because viscosity component and gel skeleton exist, solid friction is changed into fluid friction (or fluid friction); Due to the existence of gel micro-ball, one layer or more spheroid can be filled at contact surface, solid friction is transformed into rolling friction or pivoting friction.Therefore can show that adding of gel not only effectively can reduce frictional force from theory, reduce the residence time of conversion between sound friction, can also reduce or get rid of that injured soft tissue attachment tube is thinning, infringement at the bottom of basin bone, vaginal tear, injury of perineum, rectal injury, uterine rupture, the risk of losing blood, and restriction or prevention long-term damage, such as: urinary incontinence, fecal incontinence, sexual dysfunction and mental maladjustment.The stripping of artificial Placenta Hominis can also be contributed to by gel of the present invention.

Solid friction

Two solid face rub mutually, captivation mutual between surface of solids atom, molecule (energy requirement of chemical bond restructuring, glue power) and the rough surface between them cause mutual between the resistance that blocks.If the Material selec-tion of two solid face is improper or the mutual very large words of applied pressure between them, so solid friction will cause wearing and tearing.When do not make with lubricator or lubricant failure can cause solid friction.

Fluid friction

Fluid between fluid in friction-producing layer relative to each other moves.The flow resistance of this inside is described to viscosity.Viscosity in daily life is " thickness ".Therefore, water is " thin ", have lower viscosity, and Mel is " thick ", has higher viscosity.The fluid that viscosity is lower, it is larger that it is convenient to motion.(except the superfluid) of all real fluids has certain crushing resistance, therefore, is viscosity, but does not have the fluid of anti-shearing stress to be called as a desirable fluid or noncohesive fluid.

$\mathrm{\τ}=\mathrm{\η}\frac{\mathrm{du}}{\mathrm{dz}}$

Rolling friction

If an object in one plane rolls, so it can be subject to rolling friction.If the frictional force between the object rolled and plane equals other all resultant moment of putting on this object, so its motion is a pure rolling movement [1], the part of wherein not sliding.

Due to pure rolling movement object and contact surface geo-stationary, this point does not have displacement in the direction of the force, so force of rolling friction does not do work.

Pivoting friction

The frictional force that ball produces when its axle perpendicular to a plane rotates is called as pivoting friction, its moment T(τ with rotational motion) relevant:

$N=\frac{T}{F_N}\mathrm{incm}$

Summary of the invention

The invention discloses a kind of brand-new preparation method of practise midwifery gel.The present invention with reference to bionic design, have wire drawing mucus, gel skeleton and gel micro-ball 3 part form, concrete formula, technique are as described below.

Formula:

Viscosity, stringiness material: other mucopolysaccharide materials such as hyaluronic acid;

Fibrous skeleton: hydroxypropyl cellulose class;

Water-soluble thickener, pro-skin, vagina are used: Carmomer;

Diluent: single charge ion solution such as NaCl, KCl;

PH stabilizing agent: acetate buffer salt;

PH adjusting agent: NaOH, KOH, lactic acid, acetic acid;

Wetting agent: propylene glycol, glycerol;

Preparation technology:

1) wire drawing mucus configures: the NaCl solution adding 5L10% in reactor 1.Slowly be sprinkled into 300g hyaluronic acid, stir 10min at 100 rpm, open vacuum, add purified water 20L while stirring, after 5min, rotating speed is increased to 200rpm Keep agitation 15min, de-bubble.At room temperature store, (stirring remains on 50rpm and do not stop) for subsequent use

2) configuration of water-based thickener: be slowly sprinkled into 200g Carmomer directly in reactor 1, stirs 10min under 75rpm, opens vacuum duration subsequently and stirs 15min, de-bubble.Rotating speed is increased to 150rpm, add 10%NaOH regulate pH to 5.5 ?5.6. Keep agitation store for subsequent use.

3) gel skeleton configuration: add 20kg propylene glycol in reactor 2, be slowly sprinkled into 4.5kg hydroxyethyl-cellulose, and be made into suspension under 75rpm, opens froth in vacuum.

50L water is added suspension, and slow height rotating speed, to 150rpm, stirs 50min and stores for subsequent use.

4) gel micro-ball preparation: 150g alginic acid is added in 5L water, obtains the liquid that concentration is 3%.

After 25kg dry ice being added nano grinder pulverizing, use ultrasonic sprayer to spray into the drop of diameter within 10 μm with the speed of 75ml/min, pulverize with dry ice mix and blend, until obtain the ice pellets that particle diameter is about 50nm

After having sprayed under vacuum conditions, improve temperature Zhi ?20～?10 DEG C, make dry ice directly biochemical, take away, obtain the ice crystal of diameter at 50nm.

In reactor 3, configure the CaCl2 solution of 4% concentration, maintain the temperature at 35 DEG C, stir under keeping 150rpm.

To in reactor 3, directly spray into nanometer ice crystal, the rapid calcification of CaCl2 solution obtain diameter 50 ?the suspension of gel micro-ball of 100nm, the stirring remaining on 100rpm is stand-by.

5) configuration of gel micro-ball agent

The gel micro-ball obtained directly is added the mucus in reactor 1, stirs at 100 rpm and form microsphere suspension.Open froth in vacuum

Microsphere suspension is added in reactor 2, under 75rpm, stir 30min, and open froth in vacuum.

By mixed liquor overnight storage at stopping being stirred in 25 DEG C.Hydroxyethyl-cellulose in the solution crosslinked association forms network structure, is locked in gel, stablizes the suspension of microsphere and sedimentation, gathering do not occur.

Accompanying drawing explanation

Fig. 1 is grain size distribution, and abscissa is particle diameter (exponentially distributing), and vertical coordinate is light intensity.

Fig. 2 is 8000 times of electron micrographs

Fig. 3 is 20000 times of electron micrographs

Fig. 4 is friction resistance curve figure, and abscissa is displacement, and vertical coordinate is frictional force

Fig. 5 is friction resistance curve figure stiction partial enlarged drawing, and abscissa is displacement, and vertical coordinate is frictional force

Specific implementation method

Embodiment 1

Formula 1

Propylene glycol: 200g/L

Hydroxyethyl-cellulose: 45g/L

Carmomer 940:2g/L

Hyaluronic acid: 3g/L(molecular weight is about 50w)

Purified water: supply 1L

NaOH:10%(mass concentration) regulate pH to 5.5 ?5.6

Acetate buffer salt: the acetate buffer solution (acetic acid of 4.8ml0.2mol/l adds the sodium acetate of 45.2ml0.2mol/l) of 1.6%, pH about 5.6

Preparation technology:

Mucus configures:

A wire drawing mucus configures: the Nacl solution adding 5L10% in reactor 1.Slowly be sprinkled into 300g hyaluronic acid, stir 10min at 100 rpm, open vacuum, add purified water 20L while stirring, after 5min, rotating speed is increased to 200rpm Keep agitation 15min, de-bubble.At room temperature store, (stirring remains on 50rpm and do not stop) for subsequent use

The configuration of B water-based thickener: be slowly sprinkled into 200g Carmomer directly in reactor 1, stirs 10min under 75rpm, opens vacuum duration subsequently and stirs 15min, de-bubble.

Rotating speed is increased to 150rpm, add 10%NaOH regulate pH to 5.5 ?5.6. Keep agitation store for subsequent use

Gel skeleton configures:

C framework configures: in reactor 2, add 20kg propylene glycol, be slowly sprinkled into 4.5kg hydroxyethyl-cellulose, and be made into suspension under 75rpm, opens froth in vacuum.

50L water is added suspension, and slow height rotating speed, to 150rpm, stirs 50min and stores for subsequent use.

Prepared by gel micro-ball:

Prepared by D gel micro-ball: be added in 5L water by 150g alginic acid, obtain the liquid that concentration is 3%.

After 25kg dry ice being added nano grinder pulverizing, use ultrasonic sprayer to spray into the drop of diameter within 10 μm with the speed of 75ml/min, pulverize with dry ice mix and blend, until obtain the ice pellets that particle diameter is about 50nm

After having sprayed under vacuum conditions, improve temperature Zhi ?20～?10 DEG C, make dry ice directly biochemical, take away, obtain the ice crystal of diameter at 50nm.

In reactor 3, configure the CaCl2 solution of 4% concentration, maintain the temperature at 35 DEG C, stir under keeping 150rpm.

To in reactor 3, directly spray into nanometer ice crystal, the rapid calcification of CaCl2 solution obtain diameter 50 ?the suspension of gel micro-ball of 100nm, the stirring remaining on 100rpm is stand-by.

The configuration of gel micro-ball agent:

The gel micro-ball obtained directly is added the mucus in reactor 1, stirs at 100 rpm and form microsphere suspension.Open froth in vacuum

Microsphere suspension is added in reactor 2, under 75rpm, stir 30min, and open froth in vacuum.

By mixed liquor overnight storage at stopping being stirred in 25 DEG C.Hydroxyethyl-cellulose in the solution crosslinked association forms network structure, is locked in gel, stablizes the suspension of microsphere and sedimentation, gathering do not occur.

Embodiment 2

Formula 2

Propylene glycol: 200g/L

Hydroxyethyl-cellulose: 45g/L

Carmomer 980:2g/L

Hyaluronic acid: 3g/L(molecular weight is about 15w)

Purified water: supply 1L

NaOH:10%(mass concentration) regulate pH to 5.5 ?5.6

Acetate buffer salt: the acetate buffer solution (acetic acid of 4.8ml0.2mol/l adds the sodium acetate of 45.2ml0.2mol/l) of 1.6%, pH about 5.6

Preparation technology is see embodiment 1.

Experimental example 1 microspherulite diameter measures

Use Malvern ZS90, software: Zetasizer Software7.02, condition determination: retarder thinner: water, Materal RI:1.59, solvent refractive index: 1.330, cycle-index: 3 times, viscosity (cP): 0.8872, absorbed value: 0.010, temperature (DEG C): 25.0, circulating continuancing time (s): 80, sample rate (kcaps): 149.2, measuring position (mm): 4.65, pond: glass cuvette, attenuator: 6.Measurement result is shown in Fig. 1 in table 1 and measurement result curve; In Fig. 1, abscissa is particle diameter (exponentially distributing), and vertical coordinate is light intensity.

Table 1 calcium alginate microsphere particle size distribution

		Diameter (d.nm)	% light intensity	Standard deviation (d.nm)
					Mean diameter: 63.78	Peak 1:	65.99	100.0	13.83
Particle size distribution: 0.002	Peak 2:	0.000	0.0	0.000
					Intercept: 0.965	Peak 3:	0.000	0.0	0.000
Evaluation of result: good

From table 1 result, obtained calcium alginate microsphere mean diameter is 65.99nm, and within the scope of 50 ~ 100nm, particle size distribution PDI:0.002, distribution is very narrow, belongs to narrow point point.This technical maturity is described, the calcium alginate microsphere of 50 ~ 100nm can well be obtained, and it is homogeneous to distribute.

Use ultramicroscope pictures taken, Fig. 2 is 8000 times, and Fig. 3 is 20000 times.

As can be seen from electron micrograph Fig. 2 and Fig. 3, calcium alginate microsphere soccer star rule, rounding, surface compact.From the enlarged drawing of 20000X can estimate (with scale estimation) particle diameter about 60 ?70nm, coincide with the measurement result of laser particle analyzer.

The measuring of experimental example 2 lubricity

The FT1 high accuracy friction coefficient instrument of Britain Lloyd is adopted to simulate, evaluate the lubricant effect of gel herein.By literature search, we recognize some key parameters.

The key parameter of table 2 birth canal simulation

The stages of labor persistent period	13h	Uterine contraction frequency	120s/ time
				The uterine contraction persistent period	70 ~ 90s/ time	Residence time
Birth canal temperature	37℃	Bony pelvis gradient	60°
				Bispinous diameter	10cm	Anteroposterior diameter of midpelvis	11.5cm
Soft birth canal length	7～10cm	Birth canal pressure	30kPa
				Newborn skin water content	74.5%	Soft birth canal moisture content of skin	69.4%
Fetus body is long	50cm	Translational speed

In actual measurement process adopt 25 DEG C, relative humidity be 25 ?35% environment.Use fresh pig birth canal skin to cover at flaggy upper surface, use little porcine skin illiteracy at the lower surface of slide block, make moisture content of skin control 70%, slide block increases counterweight, produce the normal pressure of 30kPa, with the speed moving slider of 3 ?8cm/h, draw out as lower curve is shown in Fig. 4.

Dotted line is amniotic fluid matched group (replacing amniotic fluid with 11ml normal saline), and solid line is gel group, smears 4ml gel.Represent between mesozone that kinetic force of friction is interval.From Fig. 4, obviously can find out that the use of gel decreases kinetic force of friction.

Also find in actual measurement process under the pressure of 30kPa gel formed between two-layer skin thickness about 0.24 μm lubricating layer (adopt Filmetrics company F3 ?CS ?UV coherent light Instrument measuring).And along with the increase amniotic fluid matched group pressure of pressure often increases 10kPa, force of sliding friction increases 1.5N, and the coefficient of sliding friction is 0.15.Gel sample group pressure often increases 10kPa, and force of sliding friction increases 0.5N, and the coefficient of sliding friction is 0.05.Coefficient of friction reduces obviously, sees Fig. 5.

As can be seen from Figure 5, there is significantly quiet, kinetic force of friction conversion process in amniotic fluid matched group, figure shows as after frictional force raises fast and fall after rise to force of sliding friction.The conversion process that gel sample group does not then have obvious sound to rub.

Experimental example 3 zoopery

1, local irritation test

This test example test group test sample is that the embodiment of the present invention 1,2 makes gained obstetric canal lubrication composition gel by oneself, matched group test sample HappyChildBirth company gel.

Test method: get healthy mice 48, female, be divided into test group, matched group complete vagina group and damaged vagina group at random, totally 6 groups, often organize 8; Test group and matched group complete vagina group be difference even application test sample 1.0g in the vaginal orifice of each animal to intravaginal; Test group and the damaged vagina treated animal of matched group, within first 12 hours, insert vagina respectively with the circular file of the blunt circle in front end in administration, pass in and out 5 times, friction causes vagina damaged, degree of injury should be consistent, and gives test sample respectively more afterwards by method described in complete vagina group; Each group of every day is administered once, continuous 7 days, after not secondary administration 24 hours, and whether have hyperemia, erythema, edema or secretions etc., put to death animal, win vagina, use physiology salt if observing animal skin of vulva

Water rinses rear perusal administration place vaginal mucosa well with or without irritant reaction symptoms such as hyperemia, erythema and edema, carries out stimulation evaluation methodology: local irritation reaction standards of grading and evaluation criterion are as table 3,4.

Table 3 local irritation reaction standards of grading

Erythema	Score value	Edema	Score value	Secretions	Score value
						Without erythema	0	Without edema	0	Without secretions	0
Micro-erythema	1	Micro-edema	1	Differential secretion	1
						Slight erythema	2	Mild edema	2	Slight secretions	2
Moderate erythema	3	Intermediate edema	3	Poisoning secretions	3
						Severe erythema	4	Severe edema	4	A large amount of secretions	4

Table 4 local irritation evaluation criterion

Score value	Evaluate
		0	Nonirritant
1～3	Microstimulation
		4～6	Slight zest
7～9	Poisoning zest
		10～12	Obvious irritation

Table 5 local irritation evaluation result

As known from Table 5, the gel described by the embodiment of the present invention 1,2 combines damaged vagina group evaluation result at complete vagina and is nonirritant, and matched group combines damaged vagina group evaluation result at complete vagina and is microstimulation.

2, vagina local anaphylaxis test

This test example test group test sample is that the embodiment of the present invention 1,2 makes gained obstetric canal lubrication composition gel by oneself, matched group test sample HappyChildBirth company gel.

Test method: get Cavia porcellus 120, female, body weight 250 ~ 300g, after laboratory is fed and is conformed for 3 days,

Be divided into test group and matched group at random, often organize 40, respectively once induced respectively at other medicine of Cavia porcellus vagina 1.5cm place coating 1.0g respective sets at the 0th, 7 and 14 day, within after sensitization 1,24 hour, observe each group of whole body and pudendum anaphylaxis situation; 28th day, again each treated animal is induced as stated above, then in 24,48h observes Cavia porcellus systemic anaphylaxis situation, put to death animal subsequently, vagina is cut, after normal saline flushing in vertical face, observe vaginal mucosa anaphylaxis, mark by table 5 standard, calculate average anaphylaxis score value and sensitization rate (allergic animal number/all animals × 100%), evaluate sensitization degree by table 6.

Evaluation methodology: vagina local anaphylaxis reaction standards of grading and evaluation criterion are as table 6,7, and evaluation result is in table 8.

Table 6 vagina local anaphylaxis reaction standards of grading

Reaction Qiang Du ?congested	Score value	Reaction Qiang Du ?edema	Score value
				Without congested	0	Without edema	0
Mild hyperaemia	1	Mild edema	1

Moderate is congested	2	Intermediate edema	2
				Severe is congested	3	Severe edema	3
Edema is also congested	4

Table 7 vagina local anaphylaxis reaction evaluating standard

Sensitization rate (%)	Classification	Degree of allergic reaction
			0～8	I	Micro-sensitization
9～28	II	Slight sensitization
			29～64	III	Moderate sensitization
65～80	IV	Strong sensitization
			81～100	V	Extremely strong sensitization

Table 8 vagina local anaphylaxis evaluation result

3, fetal toxicity test

This test example test group test sample is that the embodiment of the present invention 1,2 makes gained obstetric canal lubrication composition gel by oneself, matched group test sample HappyChildBirth company gel.

Test and evaluation methodology: with reference to once cherishing the method in document study on tributyltin chloride on cultured mouse embryos in vitro toxicity research one literary composition such as, Chen Feng, carry out the evaluation of fetal toxicity test and result thereof.

It should be noted that, the final concentration of this test example test group and matched group culture fluid is equivalent in high molecular polymer, and concentration is 0.50mg/mL, 1.00mg/mL, 3.00mg/mL, and under each concentration, test group and matched group all use 15 embryos.

Result of the test: mice embryonic toxicity test result is as table 9.

Table 9 mice embryonic toxicity test result

As seen from the results in Table 9, inventive gel Mouse Embryo Development situation and test sample HappyChildBirth company at various concentrations gel embryo's independent aspects data closely, statistically a little more than test sample.

Show with crossing above-mentioned three treated animal tests, gel of the present invention has the safety a little more than import commercially available product.

Claims (2)

1. a practise midwifery gel, comprises propylene glycol: 200g/L, hydroxyethyl-cellulose: 45g/L; Carmomer 940 or Carmomer 980:2g/L; Hyaluronic acid: 3g/L(molecular weight is about 50w); Purified water: supply 1L; NaOH:10%(mass concentration) regulate pH to 5.5-5.6; Acetate buffer salt: the acetate buffer solution (acetic acid of 4.8ml0.2mol/l adds the sodium acetate of 45.2ml0.2mol/l) of 1.6%, pH about 5.6.

2. a preparation method for practise midwifery gel, its step is as follows:

1) wire drawing mucus configures: the NaCl solution adding 5L10% in reactor 1, is slowly sprinkled into 300g hyaluronic acid, stirs 10min at 100 rpm, open vacuum, add purified water 20L while stirring, after 5min, rotating speed is increased to 200rpm Keep agitation 15min, de-bubble; At room temperature store, for subsequent use, stirring remains on 50rpm and does not stop;

2) configuration of water-based thickener: be slowly sprinkled into 200g Carmomer directly in reactor 1, stirs 10min under 75rpm, opens vacuum duration subsequently and stirs 15min, de-bubble; Rotating speed is increased to 150rpm, and add 10%NaOH and regulate pH to 5.5-5.6, Keep agitation stores for subsequent use;

3) skeleton configuration: add 20kg propylene glycol in reactor 2, be slowly sprinkled into 4.5kg hydroxyethyl-cellulose, and be made into suspension under 75rpm, opens froth in vacuum; 50L water is added suspension, and slow height rotating speed, to 150rpm, stirs 50min and stores for subsequent use;

4) gel micro-ball preparation: 150g alginic acid is added in 5L water, obtains the liquid that concentration is 3%; After 25kg dry ice being added nano grinder pulverizing, use ultrasonic sprayer to spray into the drop of diameter within 10 μm with the speed of 75ml/min, pulverize with dry ice mix and blend, until obtain the ice pellets that particle diameter is about 50nm; After having sprayed under vacuum conditions, temperature is improved to-20----10 DEG C, make dry ice directly biochemical, take away, obtain the ice crystal of diameter at 50nm; In reactor 3, configure the CaCl2 solution of 4% concentration, maintain the temperature at 35 DEG C, stir under keeping 150rpm; To in reactor 3, directly spray into nanometer ice crystal, obtain the suspension of diameter at the gel micro-ball of 50-100nm in the rapid calcification of CaCl2 solution, the stirring remaining on 100rpm is stand-by; The configuration of gel micro-ball agent; The gel micro-ball obtained directly is added the mucus in reactor 1, stirs at 100 rpm and form microsphere suspension; Open froth in vacuum; Microsphere suspension is added in reactor 2, under 75rpm, stir 30min, and open froth in vacuum; By mixed liquor overnight storage at stopping being stirred in 25 DEG C; Hydroxyethyl-cellulose in the solution crosslinked association forms network structure, is locked in gel, stablizes the suspension of microsphere and sedimentation, gathering do not occur.