CN104771790B - A kind of preparation method of midwifery gel - Google Patents
A kind of preparation method of midwifery gel Download PDFInfo
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- CN104771790B CN104771790B CN201410013147.4A CN201410013147A CN104771790B CN 104771790 B CN104771790 B CN 104771790B CN 201410013147 A CN201410013147 A CN 201410013147A CN 104771790 B CN104771790 B CN 104771790B
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/04—Macromolecular materials
- A61L31/042—Polysaccharides
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/04—Macromolecular materials
- A61L31/048—Macromolecular materials obtained by reactions only involving carbon-to-carbon unsaturated bonds
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L31/145—Hydrogels or hydrocolloids
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Abstract
The invention discloses a kind of new preparation method of midwifery gel.The present invention refers to bionic design, is made up of wire drawing mucus, gel skeleton and the part of gel micro-ball 3.Wire drawing mucus using sodium hyaluronate as principal component, adds Carmomer to improve skin-friendly ability, adds hydroxyethyl cellulose regulation viscosity with reference to organism lubricating fluid.Whole formula is similar to the lubricating fluid in human body, has identical viscosity, identical stringiness and pro-skin ability.Mesh skeleton gel provides very strong compressibility and film forming for system.When fetus enters birth canal, generation about 30kPa pressure, flow elasticity mucous membrane thick extruding gel-forming 0.24um.50 100nm sodium alginate gel microspheres are added in system, gel is had to the interformational sliding friction of script, it is changed into rolling friction, not only reduce sliding friction, stiction can also be effectively reduced, so as to reduce residence time, damage and pain when reducing puerpera's uterine contraction, delivery time is shortened.
Description
Technical field
The present invention relates to the preparation method of midwifery gel, belongs to biochemical field of medicaments.
Background technology
The vaginal delivery of baby is a complicated process, and woman produces medical research and proved, gives a birth by childbirth thing（Fetus, sheep
Film, placenta）, birth canal（It is made up of bone parts and soft tissue pipeline）Determine that woman produces medical research with three aspect factors such as childbirth power
Show, the power for promoting childbirth is uterine contraction and gravity, and the power for suppressing childbirth is the tension force of ostium 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.When the normal labor of primipara continues
Between 12 hours of average out to, and 8 hours of normal labor duration average out to of multipara.Compared with primipara, multipara
The average childbirth duration it is shorter the reason for be birth canal tension force reduce because the soft tissue pipeline of multipara（Internal is soft
Tissue tract（Uterus section --- canal of uterine cervix --- soft tissue attachment tube（Vagina and vulva）））By previous vaginal delivery
It is thinning.Therefore, the main theory of relevant people's childbirth mechanics is：The tension force of birth canal（Open birth canal, stretch birth canal and make birth canal thinning
Required power）It is considered as the power of important obstruction childbirth.
Pain of the puerpera during spontaneous labor is unmodifiable objective fact, due to pain of the puerpera in childbirth
And fear, birth process is full of all multi-risk Systems, huge injury can be not only caused to puerpera's body, can also make baby it is several because
Difficult labour, anoxic and cause brain injury, or even can also cause female or baby dead, therefore, many puerperas selection in childbirth is cut open the belly
Operation, but because laparotomy ventrotomy has certain risk, not only it is unfavorable for multiple extensive after parturient childbirth, nor is beneficial to baby
Growth.
The World Health Organization (WHO) repeatedly writes articles appealing and encourages spontaneous labor, reduces non-adaptive card Cesarean esction, it is proposed that will cut open
For the warning line traffic control of palace yield below 15%, WHO recent statistics in 2010 announce the state's childbirth options of 2007-2008 Asia nine
Sampling Investigation Report, it is indicated that Chinese cesarean delivery rate has reached 46.2%, and Individual hospitals are even up to 68%, wherein without Medical indication
Cesarean esction ratio turns into one of cesarean delivery rate highest country in the world, the World Health Organization suggests cesarean delivery rate up to 11%
Warning line is scheduled on 15%, and China is far apart away from this target.
Mitigate pain of the puerpera in spontaneous labor, be not only to care about, more conducively reduce the Cesarean esction of no indication, more favorably
Hazard event when childbirth is prevented, such as puerpera's body excessively injures, baby's injury, or even jeopardizes mother and baby's life.
In veterinary science, the childbirth mechanical meaning for the frictional force between thing and birth canal of giving a birth has been known for many decades.Apply
It is with lubricator the standard method [2] in veterinary assisted birth to reduce frictional force to birth canal, and lubricant for the purpose
It is commercially available.In animal is given a birth, relatively large amounts of lubrication can be used.It is possible thereby to using the aqueous compositions of liquid, its
It has been used as the amniotic fluid of lubrication or the substitute of allantoic fluid in useful animal.
One between the childbirth of animal and the childbirth of people substantially different to be：The effect of amniotic fluid and profit in people's term birth
Sliding birth canal may conversely increase caused frictional force without significant correlation.Amniotic fluid（As hydrous matter）In people
Itself is without significant lubricant effect.At present, in people, vaginal delivery is most of only to be carried out with head position, wherein blocking up due to head
Plug, the in the progress of labor discharge of amniotic fluid are considered inessential.Vernix caseosa（Unique greasing substance of childbirth thing）Major part exists
Or so expected date of childbirth is no longer present, in a word the correct effect for only having very little.Therefore, make before the vaginal delivery of people or during it
It is not intended to reduce frictional force lubricating birth canal with amniotic fluid or amniotic fluid substitute and to make one vaginal delivery readily suitable enough
Method.
The problem of childbirth of puerpera is substantially exactly frictional force.Because uterine contraction is interval sexual behaviour, therefore entirely gave a birth
The process that journey, which is actually static friction, --- dynamic friction --- between static friction constantly mutually converts, during our static between
Phase is referred to as：Residence time（dwell time）.According to formula f=μ N of frictional force in physics（F, which is that birth process is suffered, to rub
Power, μ are coefficient of friction, and N is the normal pressure suffered by birth process）.Quiet in physics, kinetic force of friction formula is identical, difference
It is in friction coefficient μ, confficient of static friction is more than the coefficient of kinetic friction in general.Therefore the continuous conversion of sound friction, also can
Product is allowed to produce the sensation that pain is constantly deepened.
United States Patent (USP) 3,814,797 discloses aqueous lubricating composition, and it is based on (A) potassium metaphosphate, (B) alginic acid, carboxylic
Methylcellulose, CMS and its salt, and the sodium salt of (C) weak acid, such as sodium carbonate or sodium phosphate；
United States Patent (USP) 3,971,848 discloses the lubricant compositions for mucous membrane, and it contains fucoidin and alginates
Mixture, said composition can be optionally with carboxymethyl cellulose, Sodium Polyacrylate, sodium polyphosphate potassium, PEO etc.
Mixing, and for making childbirth easy；
United States Patent (USP) 4,267,168 discloses a kind of liquid biocidal composition, and it can be used as cleaning agent, surface disinfectant
Or Astroglide.Said composition includes lauryl diglycollic amide, propane diols, glycerine, poly- pectic acid sodium and silver ion；
JP46,024,256 discloses a kind of lubricant compositions, and it is substantially made up of polyacrylate, and can be in beast
It is used as promotion property uterine luminal fluid in medical science；
JP45,000,153 and JP4,500,012 discloses a kind of lubrication Jing Zuhe for being used to promote childbirth in veterinary science
Thing, it includes the salt or ester and Arabic gum of alginic acid；
JP46,034,991 discloses a kind of lubricant compositions that powder is burnt comprising polycyclic oxygen second in a liquid, described
Liquid is by concentration>80% organic solvent, hydroxypropyl cellulose, sodium sulphate and detergent composition.In kind medical science, the combination
Thing can be used to contribute to the taking-up of fetus after dilution；
The organic substance that PCT/EP03/0054 is disclosed physiologically without a doubt is used to prepare the alkali for not containing metaphosphoric acid
The purposes of the composition of metal salt, the composition are used as lubricant in the vaginal delivery of women.It is referred to suitable physiology
Many examples of organic substance on without a doubt.The target of the invention is, by being reduced point using lubricant in people
Power that is being recognized in childbirth medical science, important, hindering childbirth, the i.e. frictional force between childbirth thing and birth canal；
International publication W02006/050951（China Patent Publication No. CN101087587A）Disclosing one kind makes one childbirth appearance
The easy gel combination with good adhesion property and lubrication, contains Carbomer polyacrylic acid, water-soluble cellulose
Class thickener, NMF and water etc.；
China Patent Publication No. CN102228720A discloses a kind of childbirth with lubricator, by water, sodium chloride, propane diols,
Glycerine, natrosol and xanthans composition.
But unfortunately, on the one hand, because puerpera has the physiological fluids such as amniotic fluid, blood from production in the progress of labor
Flowed out in road, often weaken the lubricant effect of lubricant compositions, the soft tissue pipeline of puerpera is for water miscible lubricant
Although being easy to clean, for the affine more preferable of the natural composition with greasy property, physiological fluid will not be made to weaken its profit
Sliding effect, therefore, the lubricant effect for the composition that above-mentioned technical proposal is provided is not good enough；And on the other hand, real feelings are sunk
It is, because the immune level of puerpera and fetus in the progress of labor is very low, birth canal meeting bleeding and often progress perineal incision art,
Very likely increase the chance locally and systemically infected in birth process, therefore, make midwifery lubricant that both there is efficient lubrication
Effect, not only safety but also there is anti-microbial property, be highly important, but antibioticses chemical substance uses in midwifery lubricant, it is past
Toward unfavorable to baby, even danger close.
Because the amniotic fluid of puerpera mainly has physiological saline and very small amount mucoprotein to form, its viscosity, skin-friendly are far from enough,
Frictional force also can not be effectively reduced in whole birth process, and can be absorbed quickly by birth canal.It can be considered that divide naturally
The frictional force of childbirth process meets " solid friction " model.Add after midwifery gel while 3 kinds of models be present：Due to viscosity into
Divide and gel skeleton in the presence of lubricating film is formed under stress, solid friction is changed into fluid friction（Or fluid friction）；Due to
The presence of gel micro-ball, one layer or more spheroid can be filled in contact surface, solid friction is transformed into rolling friction or pivoting friction.
Therefore from theory can show that the addition of gel is not only able to effectively reduce frictional force, reduction sound rub between change it is resident when
Between, can also reduce or exclude thinning injured soft tissue attachment tube, the infringement of basin bone bottom, vaginal tear, injury of perineum, rectum damage
Wound, hysterorrhexis, the risk lost blood, and limit or prevent long-term damage, such as：The urinary incontinence, incontinence of faces, sex dysfunction and
Mental handicape.The stripping of artificial placenta is also can help to by the gel of the present invention.
Solid friction
Two solid face rubs mutuallies, mutual attraction between surface of solids atom, molecule（The energy of chemical bond restructuring
Demand, glue power）And the resistance blocked from each other caused by the rough surface between them.If the material of two solid faces
Select pressure that is improper or being mutually exerted between them very greatly, then solid friction will result in abrasion.Without using
Solid friction can be caused in the case of lubricant or lubricant failure.
Fluid friction
Fluid between fluid in friction-producing layer is moved relative to each other.The flow resistance of this inside is described as gluing
Degree.Viscosity in terms of daily life is " thickness ".Therefore, water is " thin ", has relatively low viscosity, and honey is " thickness ", tool
There is higher viscosity.The relatively low fluid of viscosity, it is easy to motion bigger.All real fluids（Except superfluid）Have certain
Crushing resistance, it is sticky, but the fluid of no shearing resistance shearing stress is referred to as a preferable fluid or inviscid stream therefore
Body.
Rolling friction
If if an object in one plane rolls, then it can be by rolling friction.If the object rolled
If frictional force between plane is equal to the other all resultant moments put on the object, then its motion is one pure
Rolling movement [1], without the part of slip.
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
One ball along its perpendicular to the axle of plane rotate when caused frictional force be referred to as pivoting friction, it is with turning
The torque T of dynamic motion（τ）It is relevant：
The content of the invention
The invention discloses a kind of brand-new preparation method of midwifery gel.The present invention refers to bionic design, there is wire drawing
Mucus, gel skeleton and the part of gel micro-ball 3 are formed, and specific 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 stabilizers：Acetate buffer salt；
PH adjusting agent：NaOH, KOH, lactic acid, acetic acid；
NMF：Propane diols, glycerine；
Preparation technology：
1）Wire drawing mucus configures：5L10% NaCl solution is added in reactor 1.300g hyaluronic acids slowly are sprinkled into,
Stir 10min under 100rpm, open vacuum, add rotating speed after purified water 20L, 5min while stirring and improve to 200rpm and persistently stir
Mix 15min, de-bubble.Store at room temperature, it is standby（Stirring is maintained at 50rpm and not stopped）
2）The configuration of water-based thickener：200g Carmomers are directly slowly sprinkled into reactor 1, are stirred under 75rpm
10min, later on vacuum duration stir 15min, de-bubble.Rotating speed is improved to 150rpm, add 10%NaOH adjust pH to
It is standby that 5.5-5.6. persistently stirs storage.
3）Gel skeleton configures：20kg propane diols is added into reactor 2,4.5kg ethoxys are slowly sprinkled under 75rpm
Cellulose, and suspension is made into, open froth in vacuum.
50L water is added into suspension, slow height rotating speed to 150rpm, stirring 50min stores standby.
4）It is prepared by gel micro-ball：150g alginic acids are added into 5L water, obtain the liquid that concentration is 3%.
After 25kg dry ice is added into nano grinder crushing, sprayed into directly with 75ml/min speed using ultrasonic sprayer
Drop of the footpath within 10 μm, mix and crush with dry ice, until obtaining particle diameter about 50nm ice pellets
After having sprayed under vacuum conditions, temperature is improved to -20~-10 DEG C, is made dry ice directly biochemical, is taken away, obtains diameter
In 50nm ice crystal.
The CaCl2 solution of 4% concentration is configured in reactor 3, maintains the temperature at 35 DEG C, keeps stirring under 150rpm.
Into reactor 3, a nanometer ice crystal is injected directly into, diameter is obtained 50-100nm's in the rapid calcification of CaCl2 solution
The suspension of gel micro-ball, the stirring for being maintained at 100rpm are stand-by.
5）The configuration of gel micro-ball agent
Obtained gel micro-ball is directly added into the mucus in reactor 1, stirring at 100 rpm forms microballoon suspension.
Open froth in vacuum
Microballoon suspension is added in reactor 2,30min is stirred under 75rpm, and open froth in vacuum.
Stop stirring at 25 DEG C by mixed liquor overnight storage.Hydroxyethyl cellulose be crosslinked in the solution association formed it is netted
Structure, the suspension of microballoon is locked in gel, it is stable not settle, assemble.
Brief description of the drawings
Fig. 1 is grain size distribution, and abscissa is particle diameter（It is exponentially distributed）, ordinate 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 ordinate is frictional force
Fig. 5 is friction resistance curve figure stiction partial enlarged drawing, and abscissa is displacement, and ordinate is frictional force
Specific implementation method
Embodiment 1
Formula 1
Propane diols：200g/L
Hydroxyethyl cellulose：45g/L
Carmomer 940：2g/L
Hyaluronic acid：3g/L（Molecular weight about 50w）
Purified water：Supply 1L
NaOH：10%（Mass concentration）Adjust pH to 5.5-5.6
Acetate buffer salt：1.6% acetate buffer solution（4.8ml0.2mol/l acetic acid add 45.2ml0.2mol/l acetic acid
Sodium）, pH about 5.6
Preparation technology：
Mucus configures：
A wire drawings mucus configures：5L10% Nacl solution is added in reactor 1.300g hyaluronic acids slowly are sprinkled into,
Stir 10min under 100rpm, open vacuum, add rotating speed after purified water 20L, 5min while stirring and improve to 200rpm and persistently stir
Mix 15min, de-bubble.Store at room temperature, it is standby（Stirring is maintained at 50rpm and not stopped）
The configuration of B water-based thickeners：200g Carmomers are directly slowly sprinkled into reactor 1, are stirred under 75rpm
10min, later on vacuum duration stir 15min, de-bubble.
Rotating speed is improved to 150rpm, it is standby that addition 10%NaOH regulations pH to 5.5-5.6. persistently stirs storage
Gel skeleton configures：
C framework configures：20kg propane diols is added into reactor 2,4.5kg hydroxy ethyl fibers are slowly sprinkled under 75rpm
Element, and suspension is made into, open froth in vacuum.
50L water is added into suspension, slow height rotating speed to 150rpm, stirring 50min stores standby.
It is prepared by gel micro-ball：
It is prepared by D gel micro-balls：150g alginic acids are added into 5L water, obtain the liquid that concentration is 3%.
After 25kg dry ice is added into nano grinder crushing, sprayed into directly with 75ml/min speed using ultrasonic sprayer
Drop of the footpath within 10 μm, mix and crush with dry ice, until obtaining particle diameter about 50nm ice pellets
After having sprayed under vacuum conditions, temperature is improved to -20~-10 DEG C, is made dry ice directly biochemical, is taken away, obtains diameter
In 50nm ice crystal.
The CaCl2 solution of 4% concentration is configured in reactor 3, maintains the temperature at 35 DEG C, keeps stirring under 150rpm.
Into reactor 3, a nanometer ice crystal is injected directly into, diameter is obtained 50-100nm's in the rapid calcification of CaCl2 solution
The suspension of gel micro-ball, the stirring for being maintained at 100rpm are stand-by.
The configuration of gel micro-ball agent：
Obtained gel micro-ball is directly added into the mucus in reactor 1, stirring at 100 rpm forms microballoon suspension.
Open froth in vacuum
Microballoon suspension is added in reactor 2,30min is stirred under 75rpm, and open froth in vacuum.
Stop stirring at 25 DEG C by mixed liquor overnight storage.Hydroxyethyl cellulose be crosslinked in the solution association formed it is netted
Structure, the suspension of microballoon is locked in gel, it is stable not settle, assemble.
Embodiment 2
Formula 2
Propane diols：200g/L
Hydroxyethyl cellulose：45g/L
Carmomer 980：2g/L
Hyaluronic acid：3g/L（Molecular weight about 15w）
Purified water：Supply 1L
NaOH：10%（Mass concentration）Adjust pH to 5.5-5.6
Acetate buffer salt：1.6% acetate buffer solution（4.8ml0.2mol/l acetic acid add 45.2ml0.2mol/l acetic acid
Sodium）, pH about 5.6
Preparation technology is referring to embodiment 1.
The microspherulite diameter of experimental example 1 determines
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, material absorption value：
0.010, temperature（℃）：25.0 cycle duration（s）：80, sample rate（kcaps）：149.2, measurement position（mm）：4.65
Pond：Glass cuvette, attenuator：6.Measurement result be shown in Table 1 and measurement result curve see Fig. 1；Abscissa is particle diameter in Fig. 1（It is in
Exponential distribution）, ordinate is light intensity.
The calcium alginate microsphere particle diameter distribution of table 1
| Diameter（d.nm） | % light intensity | Standard deviation (d.nm) | ||
| Average grain diameter:63.78 | Peak 1: | 65.99 | 100.0 | 13.83 |
| Particle diameter 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:It is good |
From the result of table 1, obtained calcium alginate microsphere average grain diameter is 65.99nm, in 50~100nm scopes
It is interior, particle diameter distribution PDI：0.002, distribution is very narrow, belongs to narrow point point.Illustrate the technical maturity, can be very good to obtain
50~100nm calcium alginate microsphere, and be distributed homogeneous.
Picture is shot using electron microscope, Fig. 2 is 8000 times, and Fig. 3 is 20000 times.
Calcium alginate microsphere soccer star rule, rounding, surface compact are can be seen that from electron micrograph Fig. 2 and Fig. 3.
It can be estimated from 20000X enlarged drawing（Estimated with engineer's scale）Particle diameter is about in 60-70nm, the measure knot with laser particle analyzer
Fruit coincide.
The lubricity measuring of experimental example 2
The lubricant effect of gel is simulated, evaluated herein using Britain Lloyd FT1 high accuracy friction coefficient instrument.Pass through
Literature search is it is understood that some key parameters.
The key parameter of the birth canal of table 2 simulation
| The stages of labor duration | 13h | Uterine contraction frequency | 120s/ times |
| The uterine contraction duration | 70~90s/ times | 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 grown | 50cm | Translational speed |
25 DEG C are used in actual measurement process, relative humidity is 25-35% environment.Covered using fresh pig birth canal skin
Flaggy upper surface, covered using small porcine skin in the lower surface of sliding block, moisture content of skin control is increased weight on sliding block 70%
Code, 30kPa normal pressure is produced, sliding block is moved with 3-8cm/h speed, lower curve such as is drawn out and sees Fig. 4.
Dotted line is amniotic fluid control group（Amniotic fluid is replaced with 11ml physiological saline）, solid line is gel group, smears 4ml gels.In
Between section represent kinetic force of friction section.Substantially it can be seen that the use of gel reduces kinetic force of friction from Fig. 4.
It has also been found that gel forms about 0.24 μm of thickness between two layers of skin under 30kPa pressure in actual measurement process
Lubricating layer（Using the F3-CS-UV coherent light Instrument measurings of Filmetrics companies）.And compareed with the increase amniotic fluid of pressure
Group pressure often increases 10kPa, force of sliding friction increase 1.5N, the coefficient of sliding friction 0.15.Gel sample group pressure often increases
10kPa, force of sliding friction increase 0.5N, the coefficient of sliding friction 0.05.Coefficient of friction reduces substantially, sees Fig. 5.
From fig. 5, it can be seen that amniotic fluid control group has obvious quiet, kinetic force of friction conversion process, show as rubbing on the diagram
Wipe after power quickly raises and fall after rise to force of sliding friction.And gel sample group is then without the conversion process of obvious sound friction.
The zoopery of experimental example 3
1st, local irritation is tested
This test example test group test sample is that the embodiment of the present invention 1,2 makes gained obstetric canal lubrication composition gel, control by oneself
Group test sample HappyChildBirth companiesGel.
Test method：Healthy mice 48 is taken, female, is randomly divided into the complete vagina group of test group, control group and breakage
Vagina group, totally 6 groups, every group 8；Test group and the complete vagina group of control group are distinguished uniform in introitus to the intravaginal of each animal
Apply test sample 1.0g；Test group and control group breakage vagina group animal, 12 hours circles for using front end blunt circle respectively before administration
Shape file inserts vagina, passes in and out 5 times, and friction causes vagina damaged, and degree of injury should be consistent, and press complete vagina group again afterwards
Methods described gives test sample respectively；Each group is administered once a day, continuous 7 days, 24 hours after not secondary administration, observes animal vulva
Whether skin has hyperemia, erythema, oedema or secretion etc., puts to death animal, wins vagina, use physiology salt
Water visually observes vagina mucosa at administration whether there is the stimulate the reaction symptoms such as congested, erythema and oedema after rinsing well,
Carry out stimulation evaluation method：Local irritation reacts standards of grading and evaluation criterion such as table 3,4.
The local irritation of table 3 reacts standards of grading
| Erythema | Score value | Oedema | Score value | Secretion | Score value |
| Without erythema | 0 | Without oedema | 0 | Without secretion | 0 |
| Micro- erythema | 1 | Micro- oedema | 1 | Differential secretion | 1 |
| Slight erythema | 2 | Mild edema | 2 | Slight secretion | 2 |
| Moderate erythema | 3 | Intermediate edema | 3 | Poisoning secretion | 3 |
| Severe erythema | 4 | Severe edema | 4 | A large amount of secretion | 4 |
The local irritation evaluation criterion of table 4
| Score value | Evaluation |
| 0 | It is nonirritant |
| 1~3 | Microstimulation |
| 4~6 | Slight stimulation |
| 7~9 | Poisoning excitant |
| 10~12 | Obvious irritation |
The local irritation evaluation result of table 5
As known from Table 5, the gel described by the embodiment of the present invention 1,2 combines damaged vagina group evaluation result in complete vagina
It is nonirritant, it is microstimulation that control group combines damaged vagina group evaluation result in complete vagina.
2nd, vagina local anaphylaxis is tested
This test example test group test sample is that the embodiment of the present invention 1,2 makes gained obstetric canal lubrication composition gel, control by oneself
Group test sample HappyChildBirth companiesGel.
Test method：Cavy 120 is taken, female, 250~300g of body weight, is fed in laboratory 3 days after adapting to environment,
Test group and control group are randomly divided into, every group 40, was applied at the 0th, 7 and 14 day at cavy vagina 1.5cm
Apply the other medicine of 1.0g respective sets respectively once to be induced, 1,24 hour observation each group whole body and private parts allergic reaction feelings after sensitization
Condition；28th day, each group animal is induced again as stated above, then observe cavy systemic anaphylaxis feelings in 24,48h
Condition, animal is then put to death, indulge face and cut vagina, after normal saline flushing, vagina mucosa allergic reaction is observed, by the standard of table 5
Scored, calculate average allergic reaction score value and sensitization rate (allergic animal number/all animals × 100%), evaluate and cause by table 6
Quick degree.
Evaluation method：Vagina local anaphylaxis reacts standards of grading and evaluation criterion such as table 6,7, and evaluation result is shown in Table 8.
The vagina local anaphylaxis of table 6 reacts standards of grading
| Response intensity-hyperemia | Score value | Response intensity-oedema | Score value |
| Without hyperemia | 0 | Without oedema | 0 |
| Mild hyperaemia | 1 | Mild edema | 1 |
| Moderate is congested | 2 | Intermediate edema | 2 |
| Severe is congested | 3 | Severe edema | 3 |
| Oedema is simultaneously congested | 4 |
The vagina local anaphylaxis reaction evaluating standard of table 7
| 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 |
The vagina local anaphylaxis evaluation result of table 8
3rd, embryotoxicity is tested
This test example test group test sample is that the embodiment of the present invention 1,2 makes gained obstetric canal lubrication composition gel, control by oneself
Group test sample HappyChildBirth companiesGel.
Experiment and evaluation method：With reference to once bosom, Chen Feng etc. in document study on tributyltin chloride on cultured mouse embryos in vitro
Method in the text of toxicity research one, carry out embryotoxicity experiment and its evaluation of result.
It should be noted that the final concentration of this test example test group and control group nutrient solution is in terms of high molecular polymer
Measure, concentration 0.50mg/mL, 1.00mg/mL, 3.00mg/mL, test group and control group use 15 embryos under each concentration
Tire.
Result of the test：Mice embryonic toxicity test result such as table 9.
The mice embryonic toxicity test result of table 9
As seen from the results in Table 9, inventive gel Mouse Embryo Development situation and test sample at various concentrations
HappyChildBirth companiesGel is very close in the data of embryo's independent aspects, statistically slightly higher
In test sample.
Show with excessively above-mentioned three groups of animal experiments, gel of the present invention has the security of slightly above import commercially available product.
Claims (1)
1. a kind of midwifery gel, it is characterised in that include propane diols：200g/L, hydroxyethyl cellulose：45g/L；Acritamer 940
Or Carbopol：2g/L；Hyaluronic acid：3g/L, molecular weight about 50w；Purified water：Supply 1L；NaOH：Mass concentration is 10%
Adjust pH to 5.5~5.6；Acetate buffer salt：1.6% acetate buffer solution, pH about 5.6；The preparation process of the midwifery gel
It is as follows：
1) prepared by wire drawing mucus：5L 10% NaCl solution is added in reactor 1, is slowly sprinkled into 300g hyaluronic acids,
Stir 10min under 100rpm, open vacuum, add rotating speed after purified water 20L, 5min while stirring and improve to 200rpm and persistently stir
Mix 15min, de-bubble；Store at room temperature, standby, stirring is maintained at 50rpm and do not stopped；
2) preparation of water-based thickener：200g carbomers are directly slowly sprinkled into reactor 1,10min is stirred under 75rpm,
Later on vacuum duration stirs 15min, de-bubble；Rotating speed is improved to 150rpm, add 10%NaOH regulations pH to 5.5~
5.6, lasting stirring storage is standby；
3) prepared by skeleton：20kg propane diols is added into reactor 2,4.5kg hydroxyethyl celluloses are slowly sprinkled under 75rpm,
And suspension is made into, open froth in vacuum；50L water is added into suspension, slowly raises rotating speed to 150rpm, stirring
50min storages are standby；
4) prepared by gel micro-ball：150g alginic acids are added into 5L water, obtain the liquid that concentration is 3%；25kg dry ice is added
After entering nano grinder crushing, drop of the diameter within 10 μm is sprayed into 75ml/min speed using ultrasonic sprayer,
Mix and crush with dry ice, until obtaining particle diameter about 50nm ice pellets；After having sprayed under vacuum conditions, temperature is improved to -20
~-10 DEG C, allow dry ice directly to distil, take away, obtain ice crystal of the diameter in 50nm；4% concentration is prepared in reactor 3
CaCl2Solution, 35 DEG C are maintained the temperature at, keep stirring under 150rpm；Into reactor 3, a nanometer ice crystal is injected directly into, in CaCl2
The rapid calcification of solution obtains suspension of the diameter in 50~100nm gel micro-ball, and the stirring for being maintained at 100rpm is stand-by；
5) preparation of gel micro-ball agent：Obtained gel micro-ball is directly added into the mucus in reactor 1, stirred at 100 rpm
Form microballoon suspension；Open froth in vacuum；Microballoon suspension is added in reactor 2,30min is stirred under 75rpm, and open
Open froth in vacuum；Stop stirring at 25 DEG C by mixed liquor overnight storage；Hydroxyethyl cellulose is crosslinked association and formed in the solution
Network structure, the suspension of microballoon is locked in gel, it is stable not settle, assemble.
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| CN201410013147.4A CN104771790B (en) | 2014-01-13 | 2014-01-13 | A kind of preparation method of midwifery gel |
| CN201710337622.7A CN107412885B (en) | 2014-01-13 | 2014-01-13 | Gel for midwifery and preparation method thereof |
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| CN109316634A (en) * | 2018-10-23 | 2019-02-12 | 江苏耐雀生物工程技术有限公司 | A kind of natural bacteriostatic midwifery gel and preparation method thereof |
| CN110354317B (en) * | 2019-08-22 | 2022-02-11 | 佛山市平创医疗科技有限公司 | Preparation method of embedding liquid and preparation method of water-soluble human body lubricating liquid |
| CN110393692B (en) * | 2019-09-04 | 2023-03-31 | 广东丸美生物技术股份有限公司 | Wiredrawing plant thickening agent and preparation method and application thereof |
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| CN101087587A (en) * | 2004-11-11 | 2007-12-12 | Hcb快乐儿童出生控股股份公司 | Novel composition for easing human child birth |
| CN102240260A (en) * | 2011-05-17 | 2011-11-16 | 山东省医疗器械研究所 | Medicament for treating colpoxerosis and preparation method thereof |
| CN102784416A (en) * | 2012-08-28 | 2012-11-21 | 福州乾正药业有限公司 | Novel delivery assisting gel and preparation method and application of novel delivery assisting gel |
| CN103340824A (en) * | 2013-07-09 | 2013-10-09 | 宁波华欣医疗器械有限公司 | Midwifery gel and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CH697081A5 (en) * | 2002-01-22 | 2008-04-30 | Andreas F Dr Schaub | Composition for supporting the birth of a human fetuses. |
| CN1872026A (en) * | 2005-05-30 | 2006-12-06 | 张东军 | New medicinal preparation for vagina |
| CN103126974B (en) * | 2011-11-30 | 2018-04-10 | 王冕 | A kind of gel |
| CN103316033B (en) * | 2013-07-03 | 2015-07-15 | 康晓飞 | Gel and use thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101087587A (en) * | 2004-11-11 | 2007-12-12 | Hcb快乐儿童出生控股股份公司 | Novel composition for easing human child birth |
| CN102240260A (en) * | 2011-05-17 | 2011-11-16 | 山东省医疗器械研究所 | Medicament for treating colpoxerosis and preparation method thereof |
| CN102784416A (en) * | 2012-08-28 | 2012-11-21 | 福州乾正药业有限公司 | Novel delivery assisting gel and preparation method and application of novel delivery assisting gel |
| CN103340824A (en) * | 2013-07-09 | 2013-10-09 | 宁波华欣医疗器械有限公司 | Midwifery gel and preparation method thereof |
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| CN107412885A (en) | 2017-12-01 |
| CN104771790A (en) | 2015-07-15 |
| CN107412885B (en) | 2020-04-28 |
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