CN105030824B - A kind of application of zinc-base montmorillonite and the sterile styptic powder of ca-montmorillonite - Google Patents
A kind of application of zinc-base montmorillonite and the sterile styptic powder of ca-montmorillonite Download PDFInfo
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Abstract
The present invention relates to a kind of zinc-base montmorillonite and application of the sterile styptic powder of ca-montmorillonite in the medicine of skin wound healing is prepared.Wherein, the zinc-base montmorillonite and the sterile styptic powder of ca-montmorillonite, are made up of following raw material by mass parts：5~10 parts of zinc-base montmorillonite, 8~12 parts of ca-montmorillonite.Preparation uses zinc-base montmorillonite, ca-montmorillonite, with pharmaceutic adjuvant, medicament to be made by the technique such as high temperature hot air sterilization, mixing, aseptic subpackaged for the active ingredient of medicine of the present invention.It is administered, rapid blood coagulation and can stops blooding by external preparation for skin approach, and wound infection can be prevented, there is antibacterial, antiinflammation, and have convergence, Healing to impaired skin.
Description
Technical field
The present invention relates to a kind of application of styptic powder, more particularly to a kind of zinc-base montmorillonite and the sterile hemostasis of ca-montmorillonite
Scattered application, belongs to pharmaceutical technology field.
Background technology
Blood is a kind of red blood cell, leucocyte, particulate and hematoblastic liquid for including blood plasma and being dispersed in blood plasma
Organize, moisture, acid, lipoid, soluble electrolyte and protein are also included in blood plasma.It is a kind of special in blood plasma to be suspended in
Protein is fibrinogen, and in the case of bleeding, fibrinogen can form with water and thrombin action and not dissolve in blood
Fibrin go forward side by side one-step polymerization formed grumeleuse, prevent bleeding.Under normal circumstances, animal body (including human body) injured bleeding
When, the fibrinogen in blood can play above-mentioned function, play a part of hemostasis.
In several cases, the bleeding caused by less wound can be by the coagulation function of blood itself and additional one
A little nursing interventions and suppressed.If in other situation in the case where bleeding profusely, required specific equipment and material
Material and medical professional are rescued.The bleeding always war wound that disables is fallen in battle and usually accidental wound main causes of death,
Although armament equipment constantly upgrades in Modern War, hemostatic technique is still more traditional, mostly tourniquet wrapping Pressur hemostatic.Though only
Blood is effective, but side effect is obvious, as overlong time can cause neural paralysis, limb injury can be also caused when serious, is even resulted in
Local tissue necrosis.Quick-acting haemostatic powder first-aid equipment is that it can help war wound or tight at present in the world just in the project of Study on Acceleration
Weight accidental wound patient stops blooding immediately, and the quality time is won to send rescue to hospital.
With the raising that various countries' medical field is required hemostatic material anthemorrhagic performance, haemostatic effect more preferably material gesture is developed
It must go.First, to possess good anthemorrhagic performance as the material of bleeding-stopping dressing or styptic, excellent biocompatibility,
It is nontoxic, have no side effect, be nonirritant easily processed into type etc..Therefore, from existing condition, find excellent in nature
Biomaterial is simultaneously processed, improved just as a kind of preferably selection.Secondly, can be according to the different property of various hemostatic materials
Can, using method associated with a variety of hemostatic materials, make the more preferable anthemorrhagic performance of materials serve.In addition, hemostatic material Hemostasis
Research with hemostasis approach needs further to be strengthened, to develop the hemostatic material different from existing hemostasis approach.For the mankind
Health makes new contribution.
Chinese patent literature CN101677848A disclose it is a kind of have the non-scolecite of calcium salt added in hemostasis device and
Purposes in product, medicament described in the patent are carried out obtained by ion exchange by zeolite and water miscible calcium salt.It is well known that zeolite
A kind of natural aluminosilicate acid salt ore, it has now been found that have 40 kinds, but be less than 30 kinds through structure determination, mainly the side of having
Zeolite, laumontite, phillipsite, sodalite, modenite, heulandite, clinoptilolite, chabasie, faujasite etc., this is special
Following defect be present in profit；1st, the patent does not state which kind of zeolite used, every kind of zeolite possessed active site be it is different,
Used application direction has greatly difference；2nd, zeolite has stronger water imbibition, and the mineral matter produces higher in water absorption course
Temperature, a certain degree of fire damage can be caused；3rd, natural zeolite contains the presence of more pathogenic bacteria, and the patent is entirely prepared
Process does not describe sterile preparation process；4th, because zeolite group mineral particle is thicker, the grain of selection zeolite is not stated in that patent
Footpath, as contain larger particle in styptic is prepared, easily cause skin secondary damage, and to wound healing generation it is unfavorable because
Element.Chinese patent literature CN101104080 discloses Zeolite hemostatic dressings and its production and use, medicament described in the patent
It is that Zeolite hemostatic dressings prepared by 4A zeolites, binding agent, lignin and optional molecular sieve activation powder are raw material, institute therein
The main component and content for stating Zeolite hemostatic dressings be：Al2O3Between 25~35%, SiO2Between 30~40%, and
CaO is between 10~18%, Na2O content below 1%, particle diameter more than 0.2 in the range of less than 1mm.The invention contains
Zeolite hemostatic dressings anthemorrhagic speed is fast, sterile, apyrogeneity, no cytotoxicity, without sensitivity response, without skin irritation, user
Just and cost is low.Following defect be present in the patent：But the patent only has hemostatic function, and without the convergence and healing to wound face
Function.
At present, in existing hemostatic material, there is only to the anastalsis of wound mouth, and without the convergence to wound mouth and
Heal function, and hemostatic material be present and do not possess biocidal property etc., easily causes wound infection, it is also possible to formed with beneficial to thin
The environment of bacteria growing, wound repeated infection is caused, be not easy to heal.In a word, all there is difference in the treatment method of above prior art
The defects of degree, clinical practice is set to be very limited.To meet the clinical demand of many patients, those skilled in the art are for many years
Hemostasis powder safe efficient to seek to develop always, quality controllable, easy to use.
Montmorillonite is a kind of mineral drug, is a kind of aqueous layer silicate mineral, its unit cell is by two layers of silica four
Face body piece and one layer of aluminum oxide octahedral sheet composition, the Si belonged in its typical tetrahedron4+Can be by AL3+Displacement, in octahedra
Si4+、AL3+Easily by Mg2+、Fe2+、Fe3+、Zn2+、Mn2+Deng displacement, Montmorillonite Crystal is set to produce interlayer negative electrical charge.Montmorillonite
These features assign it and meet the distinctive expansion of water, absorption, powered and ion exchange property, are allowed to for pharmaceutically having uniqueness
Advantage.The medicine is treatment diarrhoea and digestive tract ulcer and pipe intestinal protection common drug and clinically obtained preferably
Curative effect.At present, montmorillonite preparation is mainly oral formulations, is clinically used for adult and the acute and chronic diarrhoea of children etc..So far,
Modification of Montmorillonite is used to prepare zinc-base montmorillonite and the sterile styptic powder of ca-montmorillonite not yet into zinc-base montmorillonite, ca-montmorillonite
Appear in the newspapers.
The content of the invention
In order to solve drawbacks described above of the prior art, the invention provides a kind of zinc-base montmorillonite and ca-montmorillonite without
Application of the bacterium styptic powder in the medicine of skin wound healing is prepared.
Summary of the invention
The present invention is used using zinc-base montmorillonite and ca-montmorillonite as the effective ingredient of medicine, prepares skin wound healing
Medicine, realize hemostasis, antibacterial, rush is cured and analgesic effect and good ventilative, absorbent.
Zinc-base montmorillonite that the present invention uses, ca-montmorillonite can dissociate free zinc ion, calcium ion and Meng Tuo
Stone；The medicament of sterile styptic powder is spread and spread at skin trauma, following effect can be played：(1) dissociateed in sterile styptic powder
After montmorillonite runs into blood, gel can be formed, is capable of the further outflow of repressive ground resistance hemostasis, so as to quick-acting haemostatic powder；(2) solve
The montmorillonite separated out can also adsorb the bacterium in wound, prevent the breeding of bacterium, prevent wound infection, and the gel formed exists
Wound surface and surrounding can be used as protective layer, prevent the bacterial invasion in the external world；(3) the zinc ion tool that zinc-base montmorillonite dissociates
There are antibacterial, antiinflammation, and have convergence, Healing to impaired skin；(4) calcium ion that ca-montmorillonite dissociates can contract
Short bleeding time and blood plasma recalcification time.
Detailed description of the invention
Term explanation：
Zinc-base montmorillonite (Zn- montmorillonites)：It is after montmorillonite is acidified, is soaked or eluted with water-soluble zinc salt solution and dried
It is dry, and crushed 500 mesh sieves and obtain, zinc ion therein is zinc-base montmorillonite labelled amount 5.0~9.5%；It is commercially available or by existing
There is method preparation.
Ca-montmorillonite (Ca- montmorillonites)：It is after montmorillonite is acidified, is soaked or eluted with water-soluble calcium salting liquid and dried
It is dry, and crushed 500 mesh sieves and obtain, calcium ion therein is ca-montmorillonite labelled amount 5.0~9.5%；It is commercially available or by existing
There is method preparation.
Skin trauma：Refer to due to wound or other sick and wounded cause the tissues such as skin detachment or defect, including skin occur
Scratch bleeding, scald, injury from falling down.
Room temperature：Refer to the environment temperature residing for experimental implementation, control in the range of 15~30 DEG C.
Technical scheme is as follows：
A kind of zinc-base montmorillonite and application of the sterile styptic powder of ca-montmorillonite in the medicine of skin wound healing is prepared.
According to the present invention, zinc-base montmorillonite is with the sterile styptic powder of ca-montmorillonite in the medicine of skin wound healing is prepared
Application, the application be zinc-base montmorillonite be used alone with the sterile styptic powder of ca-montmorillonite or with other medicines coordinate make
It is used as the use in conjunction of medicament.
According to the present invention, zinc-base montmorillonite is with the sterile styptic powder of ca-montmorillonite in the medicine of skin wound healing is prepared
Application, wherein, the skin trauma include skin tears bleeding, scald, injury from falling down.
According to the present invention, zinc-base montmorillonite is with the sterile styptic powder of ca-montmorillonite in the medicine of skin wound healing is prepared
Application, wherein, the zinc-base montmorillonite and the sterile styptic powder of ca-montmorillonite are made up of following raw material by mass parts：
5~10 parts of zinc-base montmorillonite
8~12 parts of ca-montmorillonite；
, according to the invention it is preferred to；
Zinc-base montmorillonite and application of the sterile styptic powder of ca-montmorillonite in the medicine of skin wound healing is prepared, its
In, the zinc-base montmorillonite and the sterile styptic powder of ca-montmorillonite, it is made up of following raw material by mass parts：
5~8 parts of zinc-base montmorillonite
8~10 parts of ca-montmorillonite；
According to the present invention, further preferred；
Zinc-base montmorillonite and application of the sterile styptic powder of ca-montmorillonite in the medicine of skin wound healing is prepared, its
In, the zinc-base montmorillonite and the sterile styptic powder of ca-montmorillonite, it is made up of following raw material by mass parts：
8 parts of zinc-base montmorillonite
10 parts of ca-montmorillonite；
Or
7 parts of zinc-base montmorillonite
9 parts of ca-montmorillonite；
Or
5 parts of zinc-base montmorillonite
8 parts of ca-montmorillonite.
Wherein described zinc-base montmorillonite, ca-montmorillonite, crushed 500 mesh sieves.
According to the present invention, described zinc-base montmorillonite is preparing skin wound healing with the sterile styptic powder of ca-montmorillonite
Application in medicine, wherein described zinc-base montmorillonite is made by the following method with the sterile styptic powder of ca-montmorillonite：
(1) the zinc-base montmorillonite of formula ratio is crushed, crosses 500 mesh sieves, be put into dry heat sterilization cabinet, temperature is 170~180
DEG C sterilizing, sterilization time is 180~240min, and it is standby to be down to room temperature；
(2) ca-montmorillonite of formula ratio is crushed, crosses 500 mesh sieves, be put into dry heat sterilization cabinet, temperature is 250~300
DEG C sterilizing, sterilization time 120min, it is standby to be down to room temperature；
(3) material for obtaining step (1), step (2) is put into sterilized mixing tank；It is stirred and is well mixed
Afterwards；It is aseptic subpackaged to produce zinc-base montmorillonite and the sterile styptic powder of ca-montmorillonite.
For preparation method, above is the preferred method of the present invention, but not limited to this.
It is not particularly limited, can refer in zinc-base montmorillonite described above and the sterile styptic powder preparation method of ca-montmorillonite
Prior art.Those skilled in the art can suitably be adjusted according to its well known knowledge.
In preparation method of the present invention zinc-base montmorillonite and the sterile styptic powder quality standard of ca-montmorillonite it is following but
Unlimited zinc-base montmorillonite as described below and the sterile styptic powder standard of ca-montmorillonite.
Zinc-base montmorillonite and the sterile styptic powder of ca-montmorillonite
This product montmorillonite containing zinc-base should be the 97.0%~105.0% of labelled amount with ca-montmorillonite；Wherein zinc ion is
Zinc-base montmorillonite and ca-montmorillonite labelled amount 3.5~5.5%, calcium ion are zinc-base montmorillonite and ca-montmorillonite labelled amount
3.5~5.5%.
【Character】This product is off-white color powder.
【Differentiate】This product 0.5g is taken, puts in tool plug bottle, adds purified water 50ml, it is 3.5~4.5 to add hydrochloric acid and adjust pH value；
Ultrasonication 20 minutes, centrifugation, filtering, after taking filter cake to put the drying 2 hours of 105 DEG C of baking oven, is put into drier about 12 hours
(fill sodium chloride saturated solution in drier, about 78%) above-mentioned test sample, is then shone x-ray powder by relative humidity at 20 DEG C
Diffraction approach (two F of annex Ⅸ of Chinese Pharmacopoeia version in 2010) determines, and records collection of illustrative plates, the X-ray diffracting spectrum Ying Yumeng of test sample
De- stone reference substance collection of illustrative plates is consistent.
【Check】It is sterile：According to version (H of the annex Ⅺ) inspection in 2010 of Sterility Test Chinese Pharmacopoeia, regulation should be met.
Granularity takes test sample 10g, accurately weighed, puts No. seven sieves.According to granularity and determination of particle size distribution (Chinese Pharmacopoeia
2010 editions E the second method lists sieve methods of annex Ⅸ) check, the accurately weighed powder weight by screen cloth, 95% should be not less than.
Other should meet every regulation under powder item.
【Content】
Zn content takes Zinc standard solution, is diluted with water that to be made in every 1ml containing about zinc be respectively 0.05 μ g, 0.1 μ g, 0.2 μ
G, 0.3 μ g, 0.4 μ g solution, are reference substance solution.
Zinc content accurately weighed this product 1.0g, it is accurately weighed, put in porcelain dish, respectively plus sulfuric acid 6ml and nitric acid 10ml, treat
After reaction completely, put and be evaporated on electric furnace, let cool to room temperature, add 20% concentration hydrochloric acid 40ml, stirred evenly with glass bar, through filter paper mistake
Filter, the distillation water washing of residue heat 3 times, filtrate merges, and puts in 100ml volumetric flasks, adds distilled water diluting to be shaken up to scale.
Precision measures 10ml solution and put in 100ml volumetric flasks, adds distilled water diluting to shake up to scale, and then to measure 10ml molten for precision again
Liquid is put in 100ml volumetric flasks, adds distilled water diluting to be shaken up to scale as need testing solution.Take reference substance solution and test sample
Solution determines absorbance respectively, calculates the Zn content in sample.
The accurately weighed this product 0.5g of calcium content；Put in porcelain dish, respectively (w/w) 6ml of enriching sulfuric acid 98% and concentrated nitric acid 65%
(w/w) 10ml, after question response is complete, puts and be evaporated on electric furnace, let cool to room temperature, add water 40ml, stirred evenly with glass bar, through filter paper
Filtering, the distillation water washing of residue heat 3 times, filtrate merges, and puts in 100ml volumetric flasks, adds distilled water diluting to be shaken to scale
It is even.Add sodium hydroxide test solution 15ml and calconum indicator 0.1g, with Calcium Disodium Versenate titrating solution (0.05mol/L)
It is titrated to solution and is changed into pure blue from aubergine.Per 1ml Calcium Disodium Versenates titrating solution (0.05mol/L) equivalent to
25mg calcium ion.
With reference to experimental example, the present invention is described further, but not limited to this.
Experimental example 1：Zinc-base montmorillonite is tested with ca-montmorillonite sterilizing
In application of the present invention, active component zinc-base montmorillonite, the ca-montmorillonite of preparation are changed by montmorillonite
Property, the layer mineral of the superfine hydrous alumino silicates composition of particle, research zinc-base montmorillonite, ca-montmorillonite sterilizing methods are true
On the premise of guarantor's zinc-base montmorillonite meets quality standard with the sterile styptic powder medicine of ca-montmorillonite, ensure zinc-base montmorillonite and calcium
Base montmorillonite styptic powder medicine can be used safely, have great strategic structural.
1st, zinc-base montmorillonite sterilizing experiment
The comparison of different dry heat temperatures and xeothermic time to zinc-base montmorillonite hot air sterilization effect, is shown in Table 1：
The zinc-base montmorillonite hot air sterilization effect of table 1 compares
Drawn by that can be analyzed in table 1：
(1) dry heat temperature in 160~170 DEG C, drying time under the conditions of 120~240min, zinc-base montmorillonite X-ray
Diffracting spectrum is consistent with reference substance collection of illustrative plates, show it is xeothermic on this condition zinc-base montmorillonite chemical constitution is not destroyed, but
Sterility test, it is against regulation；
(2) dry heat temperature is at 170~180 DEG C, the xeothermic time in 120min, zinc-base montmorillonite X-ray diffracting spectrum with it is right
It is consistent according to product collection of illustrative plates, show it is xeothermic on this condition zinc-base montmorillonite chemical constitution is not destroyed, but sterility test is not inconsistent
Close regulation；
(3) dry heat temperature is at 170~180 DEG C, and the xeothermic time is in 180~240min, zinc-base montmorillonite x-ray diffraction pattern
Spectrum it is consistent with reference substance collection of illustrative plates, show it is xeothermic on this condition zinc-base montmorillonite chemical constitution is not destroyed, sterility test,
Meet regulation；Refer to Fig. 1 zinc-base montmorillonite X-ray diffracting spectrums.
Interpretation of result:The sterilising temp of zinc-base montmorillonite is chosen to be 170~180 DEG C, and the time is 180~240min.
2nd, ca-montmorillonite sterilizing experiment
Comparison of the different dry heat temperatures and xeothermic time to ca-montmorillonite hot air sterilization effect, is shown in Table 2：
The ca-montmorillonite hot air sterilization effect of table 2 compares
Drawn by that can be analyzed in table 1：
(1) dry heat temperature is at 170~180 DEG C, drying time under the conditions of 120~240min, ca-montmorillonite X-ray
Diffracting spectrum is consistent with standard items collection of illustrative plates, show it is xeothermic on this condition ca-montmorillonite chemical constitution is not destroyed, but
Sterility test, it is against regulation；
(2) dry heat temperature is at 250~300 DEG C, and the xeothermic time is in 120min, ca-montmorillonite X-ray diffracting spectrum and mark
Quasi- product collection of illustrative plates is consistent, show it is xeothermic on this condition ca-montmorillonite chemical constitution is not destroyed, refer to Fig. 2 calcium Ji Mengtuo
Stone X-ray diffracting spectrum, sterility test, meet regulation；
(3) dry heat temperature is at 250~300 DEG C, and the xeothermic time is in 180~240min, ca-montmorillonite x-ray diffraction pattern
Spectrum with standard items spectral contrast, show it is xeothermic on this condition ca-montmorillonite chemical constitution is destroyed, sterility test, accord with
Close regulation.
Interpretation of result:The sterilising temp of ca-montmorillonite is chosen to be 250~300 DEG C, time 120min.
Experimental example 2：Zinc-base montmorillonite and ca-montmorillonite rabbit Skin Irritation Test
1st, test material
(1) medicine：The zinc-base montmorillonite of Example 1 does this reality with the sterile styptic powder of ca-montmorillonite as test sample
Test, it is stand-by.
(2) animal：The Japanese white big ear rabbit of health, 2.0~2.4kg of weight, male and female half and half, tested by Shandong University dynamic
Thing center provides.
(3) method
Rabbit 6 is only randomly divided into intact skin group and damaged skin group by sex body weight, every group 3.24h is by family before administration
Rabbit ridge both sides symmetric depilation, depilation area are 10% (per side scope about 50cm) of rabbit body surface area.Left side is that A areas are (empty
White check plot), B areas (70% ethanol control area), right side is that (zinc-base montmorillonite is administered with the sterile styptic powder of ca-montmorillonite in C areas
Test block).A areas are coated with distilled water 0.5mL, B areas and are coated with 70% ethanol 0.5mL, right side C on the left of 24h intact skins group after depilation
Area with zinc-base montmorillonite and the sterile styptic powder of ca-montmorillonite, three times a day.Then with after one layer of plastic paper and two layers of gauze covering
Fixed with self-control rabbit set.Damaged skin group is worn with syringe needle on hair removal section skin before administration, to abrade epidermis, not hinder very
Skin, slight oozing of blood are degree, and medication is the same as intact skin group.Covering is removed after the fixed 6h of administration, observation medicine-feeding part occurs
Erythema and oedema situation.It is daily to smear 1 time, continuous 7 days.
Evaluation method：Carried out respectively by table 3, table 4 stimulate the reaction and stimulus intensity scoring, evaluation multiple dosing to completely with
The stimulus intensity of damaged skin, the recovery situation of stimulate the reaction and time, and relatively it is shown in Table 5 with control group.React average value
Computational methods form total score and divided by total with experimental animal is organized for erythema formation total score with oedema.
The skin wound repair standards of grading of table 3
The skin irritatin intensity ratings standard of table 4
Table 5 scores rabbit intact skin and damaged skin excitant
2nd, result
After continuous 7 days skin gives zinc-base montmorillonite and the sterile styptic powder of ca-montmorillonite and excipient respectively, complete skin
Skin and damaged skin occur without erythema and oedema, and skin wound repair intensity is respectively less than 0.5 point.Embrocate medicine within 1 week after drug withdrawal
And its equal non-pigment in excipient position is calm, epidermatic atrophy and it is coarse phenomena such as.Show zinc-base montmorillonite and ca-montmorillonite without
The multiple successive administration of bacterium styptic powder is nonirritant to rabbit intact skin and damaged skin, belongs to nonirritant medicine, clinical practice
Safety.
Experimental example 3：Zinc-base montmorillonite and the allergic experiment of ca-montmorillonite rabbit
1st, experiment material
(1) medicine：The zinc-base montmorillonite of Example 1 does this reality with the sterile styptic powder of ca-montmorillonite as test sample
Test, it is stand-by.
(2) animal:Healthy male Wistar rat, 250~300g of body weight, provided by Shandong University's Experimental Animal Center.
2nd, experimental method
Wistar mouse 12, are divided into intact skin and damaged skin allergic experiment group, every group 6.Every rat presses 30mg/
Kg dosage is performed the operation after yellow Jackets anesthesia is given in intraperitoneal injection.First cut rear chemical method and take off in every rat back both sides
Hair, unhairing scope is per side about 4cm × 6cm.Every animal of damaged skin group is with the knife blade that sterilizes, in unhairing zoning " well " word,
To scratch epidermis oozing of blood as degree.
1. sensitization contact：Right side goes to hair-fields to apply by reagent 0.2g, and left side applies physiological saline 0.2mL and compared, with sterilization nothing
Excitant hospital gauze cover, immobilization with adhesive tape, every animal sub-cage rearing, experiment be coated with sustained drug effect 6h, the 7th day and
Respectively it is repeated 1 times within 14th day, this stage is sensitization contact.
2. excite contact：The 14th day after last coating sensitization, then it is coated with by reagent 0.2g 1 time, removes reality after continuing 6h
Test medicine to observe at once, then 24h, 48h, 72h observe cutaneous anaphylaxis situation again.This stage is to excite contact.In
After last coating the 14th day, the reaction such as hyperemia, oedema, scleroma, necrosis is whether there is.Local skin reaction feelings are observed during whole experiment
Condition (whether there is rubescent, erythema and oedema), and whether there is special circumstances and occur occurring with allergy.Observe the appetite, OK of animal
Have for activity, to external world's reaction without exception.Allergic reaction scoring is made according to response situation, obtains the average mark of each group animal,
Data t test evaluation group differences.
3rd, experimental result
Diet, the behavioral activity of two groups of rats are normal, and no special circumstances and allergy occur, to external world's reaction just
Often.Tested group and control rats skin are formed without erythema and oedema, tested group and control rats dermoreaction value be all 0,
Sensitization rate is 0, and no allergic reaction, zinc-base montmorillonite is with the sterile styptic powder of ca-montmorillonite to rat skin without sensitization.
4th, experiment conclusion
Zinc-base montmorillonite is with ca-montmorillonite styptic powder to rat intact skin and damaged skin without allergic reaction, table
Its bright toxicity is low, Small side effects, and drug safety is reliable.
Experimental example 4：Zinc-base montmorillonite and the sterile styptic powder bacteriostatic activity research experiment of ca-montmorillonite
1st, Mlc
For zinc-base montmorillonite with containing zinc-base montmorillonite in the sterile styptic powder of ca-montmorillonite, zinc-base montmorillonite can be thin with bacterium
The memebrane protein of after birth combines, and when it is contacted with bacterium, zinc ion can slowly release, and destroy the structure of bacterium, go forward side by side
Enter to destroy the enzyme of electron transport system in its cell, while reacted with DNA, play bactericidal action.After bacterium is killed, zinc ion
Come out from endocellular liberation, repeat above-mentioned sterilization process and find, zinc-base montmorillonite has lasting bacteriostatic activity.
Table 6 is listed with tetracycline (s) as reference substance, and various concentrations zinc-base montmorillonite is (real with ca-montmorillonite styptic powder
Example 1 is applied to prepare) to (A) staphylococcus aureus；(B) EHEC；(C) pseudomonas aeruginosa；(D) salmonella is antibacterial
Situation, M are the mass concentration of zinc-base montmorillonite and ca-montmorillonite styptic powder, wherein M1=0.002g/mL, M2=0.006g/
ML, M3=0.02g/mL, M4=0.2g/mL, antibacterial circle diameter (mm) size represent the power of bacteriostatic activity, are shown in Table 6.
Table 6 is various concentrations zinc-base montmorillonite antibacterial circle diameter (mm)
As shown in Table 6, mass concentration is that 0.001 and 0.005g/mL zinc-base montmorillonite has certain bacteriostatic activity, works as zinc-base
When the mass concentration of montmorillonite is 0.02 and 0.2g/mL, bacteriostatic activity is essentially identical, no significant difference, shows as zinc-base covers
De- stone and the increase of the sterile styptic powder styptic powder mass concentration of ca-montmorillonite, its bacteriostatic activity reach a stationary value, zinc-base
Montmorillonite and the antibacterial valid density of the sterile styptic powder of ca-montmorillonite are 0.02g/mL.
2nd, bacteriostatic activity
(1) ca-montmorillonite, (2) na-montmorillonite, (3) zinc-base montmorillonite and the calcium base that mass concentration is 0.02g/ml cover
The de- sterile styptic powder of stone is listed in table 7 to the bacteriostatic activity of 4 kinds of bacteriums.
Table 7 is various montmorillonite antibacterial circle diameters (mm)
As shown in Table 7, the bacteriostatic activity of zinc-base montmorillonite is significantly higher, has compared with ca-montmorillonite and na-montmorillonite
Significant difference, and scope of restraining fungi is wider than tetracycline for these four bacterium.
Experimental example 5：Zinc-base montmorillonite is ground with the sterile styptic powder of ca-montmorillonite to wound convergence, the histology of Healing
Study carefully experiment
Wound healing refer to body due to wound or other it is sick and wounded cause the tissues such as skin detachment or defect occur after, it is local
One of the problem of tissue by regeneration, reconstruction repair a series of pathophysiological processes of recovery, and it is most basic in medical science,
Simultaneously and surgical field is devoted for years to the important clinical research topic in exploration.Present invention selection is with hemostasis, antibacterial, rush
Enter the zinc-base montmorillonite and ca-montmorillonite powder of wound healing effect, and the technology observation of application Pathological experiment is in wound healing
In journey on wound tissue influence histological change and inquire into its mechanism, for clinically explore one promotion wound healing it is effective
Approach, and provide reliable experimental basis for skin wound healing clinical research.
1st, material and method
1.1 material
Experimental animal：Healthy rabbits 24, male and female half and half, 2.5~3.0kg of body weight (is purchased from Shandong University's non-clinical study
Center)；
Medicine：Zinc-base montmorillonite is prepared with the sterile method of styptic powder embodiment 1 of ca-montmorillonite；
1.2 experimental method
Method for building animal model：With surgical cut method modeling, modeling the previous day man rabbit back is lost hair or feathers with 8% vulcanized sodium
Preserved skin.2% yellow Jackets of preoperative intraperitoneal injection (30mg/kg), rabbit prone position, after conventional iodophor disinfection, hit exactly away from backbone
Side is opened and skin holostrome otch is done at 2cm, area about 2cm × 2cm, totally 6, each 3 of left and right, surface of a wound interval about 2cm.Use physiology salt
Water irrigates, standby after sterilization.
Experimental animal is grouped：Rabbit is randomly divided into three groups：Blank group (i.e. saline treatment group), experimental group l (i.e. montmorillonites
Group) and experimental group 3 (zinc-base montmorillonite and the sterile styptic powder group of ca-montmorillonite), every group is 8, gives physiology salt respectively
Water, montmorillonite, zinc-base montmorillonite and the sterile styptic powder of ca-montmorillonite are treated.I.e. postoperative 3rd, 5,7 and 10 day group and wound are certainly
Right healing group.
Materials：Four groups of rabbit take full thick skin group in the 3rd, 5,7,10 day after surgery respectively at wound far from edge about 0.2cm
Knit.Partly fixed in time with 4% paraformaldehyde in taken tissue, 4 DEG C preserve paraffin section and HE, Masson dyeing to be done.
The observation of wound healing time：5% or the healing area that wound healing standard is less than the gross area with surface of a wound area are big
It is healing completely in 95%.
The observation of wound healing speed：Each group animal is respectively the 3rd after wound, 5,7,10 days, with 0.25cm's × O.25cm
Transparent graph paper determines wound area, and wound area, wound healing speed are calculated with Germany's production ASM.68K semi-automated image analysis instrument meter
Rate=healing area/former wound area.
Statistical procedures：With SAS6.12 statistical procedures softwares, statistical procedures are carried out to various data.
2nd, experimental result
2.1 ordinary circumstance：All animals about 2~4h after anesthesia revives, and comes into play, ad lib, water inlet.The nursing phase
Between animal activity it is good, appetite can, body weight is relatively stable.
2.2 wound healing rates：From Table 1 and Table 2, postoperative 3rd day, saline treatment group, montmorillonite, zinc-base montmorillonite with
The sterile styptic powder group of ca-montmorillonite compares.Postoperative 10th day, blank group (saline treatment group), montmorillonite group, zinc-base montmorillonite
Compared with the sterile styptic powder group of ca-montmorillonite, 8, table 9 is shown in Table；
The comparison of the postoperative 3rd day wound healing rate of table 8(%)
Note：Montmorillonite compared with blank group (saline treatment group),﹡P ＜ 0.05；Zinc-base montmorillonite and ca-montmorillonite are sterile
Styptic powder p ＜ 0.05 compared with montmorillonite；Zinc-base montmorillonite and the sterile styptic powder of ca-montmorillonite and blank group (saline treatment
Group) compare,﹡ ﹡P ＜ 0.01；
The comparison of the postoperative ten day wound healing rate of table 9(%)
Note：Montmorillonite compared with blank group (saline treatment group),﹡P ＜ 0.05；Zinc-base montmorillonite and ca-montmorillonite are sterile
Styptic powder p ＜ 0.05 compared with montmorillonite；Zinc-base montmorillonite and the sterile styptic powder of ca-montmorillonite and blank group (saline treatment
Group) compare,﹡ ﹡P ＜ 0.01；
This experiment is obtained by observing the sterile styptic powder of zinc-base montmorillonite and ca-montmorillonite to the facilitation of wound healing
Go out some following conclusion：
1. montmorillonite can promote wound healing, reduce tissue fluid and ooze out, the surface of a wound is dried, and can mitigate topical wounds oedema journey
Degree, accelerate granulation tissue generation, healing acceleration, the purpose of convergence myogenic can be reached, diaphragm, prevention infection are formed in the surface of a wound.
2. the zinc ion that zinc-base montmorillonite dissociates can strengthen phagocyte phagocytic function, chemotactic vigor and sterilizing function,
And the Free Radical Level in phagocyte is kept by superoxide dismutase, bactericidal action is played, accelerates the healing of wound；
Other zinc ion energy precipitating proteins, external application have convergence antisepsis, help granulation tissue to be formed；Improve wound healing quality；
The calcium ion that wherein ca-montmorillonite dissociates can shorten bleeding time and blood plasma recalcification time.
3. zinc-base montmorillonite is with ca-montmorillonite by promoting epidermal cell, vascular endothelial cell and fibroblast proliferation
Differentiation carrys out accelerating wound healing effect and is better than alone montmorillonite, and its zinc-base montmorillonite slowly discharges zinc ion in epidermis, so as to have
Effect is played to greatest extent beneficial to montmorillonite；The two combine be expected to as a kind of medicinal application of new promotion wound healing in
Clinic, there is good clinical application prospect.
Experimental example 6：Zinc-base montmorillonite is tested with zinc ion release, calcium ion release in ca-montmorillonite powder
1st, reagent and instrument
1.1 medicine：It is prepared by zinc-base montmorillonite and the sterile styptic powder of ca-montmorillonite, embodiment 1,2,3；
1.2 instrument：Ultraviolet specrophotometer, intelligent dissolving-out tester；
2nd, the measure of release
Zinc ion release takes this product 1g, and by the first method in two annex XC of Chinese Pharmacopoeia 2010 edition, rotating speed is
100rpm, dissolution medium are that temperature is (37 ± 0.5) DEG C with phosphate buffer (pH6.8) 1000ml, respectively at 1,1.5,2,
2.5th, 5ml is sampled at 3h time points, while supplements the dissolution medium 5ml of equality of temperature；After the sample filtering with microporous membrane of taking-up, put
In 100ml volumetric flasks, distilled water diluting is added to be shaken up to scale.Then precision measures 10ml solution and put in 100ml volumetric flasks again,
Distilled water diluting is added to be shaken up to scale as need testing solution.Reference substance solution is taken to determine absorbance respectively with need testing solution,
Calculate the Zn content in sample.It the results are shown in Table 10.
The embodiment sample different time points zinc ion of table 10 adds up release rate (%)
With the time, (hour h) makees curve to the zinc ion Cumulative release amount (%) of three batches, produces the accumulative release of each sample
Curve, as a result see accompanying drawing 3.
Calcium ion release takes this product 1g, and by the first method in two annex XC of Chinese Pharmacopoeia 2010 edition, rotating speed is
100rpm, dissolution medium are that temperature is (37 ± 0.5) DEG C with phosphate buffer (pH6.8) 1000ml, respectively at 1,2,3,4h
5ml is sampled at time point, while supplements the dissolution medium 5ml of equality of temperature；After the sample filtering with microporous membrane of taking-up, 100ml appearances are put
In measuring bottle, distilled water diluting is added to be shaken up to scale.Then precision measures 10ml solution and put in 100ml volumetric flasks again, hydrogenation oxidation
Sodium test solution 15ml and calconum indicator 0.1g, solution is titrated to Calcium Disodium Versenate titrating solution (0.05mol/L)
It is changed into pure blue from aubergine.Per calcium of the 1ml Calcium Disodium Versenates titrating solution (0.05mol/L) equivalent to 25mg from
Son, it the results are shown in Table 11.
The embodiment sample different time points calcium ion of table 11 adds up release rate (%)
With the time, (hour h) makees curve to the calcium ion Cumulative release amount (%) of three batches, produces the accumulative release of each sample
Curve, as a result see accompanying drawing 4.
Interpretation of result：Zinc-base montmorillonite and the montmorillonite dissociateed in the sterile styptic powder of ca-montmorillonite in the present invention
Damaged skin protective agent is used as again as slow-release material, zinc, calcium ion is slowly discharged, is reduced zinc, calcium ion
To the stimulation of skin；On the other hand have very strong covering protection ability to damaged skin, improve skin barrier to attack because
The defence capability of son and the effect of local skin sparing.
Experimental example 7：Zinc-base montmorillonite is with ca-montmorillonite to animal skin acute toxicity testing
1st, medicine：Zinc-base montmorillonite is prepared with the sterile styptic powder of ca-montmorillonite by embodiment 2, is placed in mortar and is ground into carefully
Powder, it is stand-by.
2nd, animal：The Japanese white big ear rabbit of health, 2.0~2.4kg of weight, male and female half and half, tested by Shandong University dynamic
Thing center provides.
(1) method
Rabbit 16 is only randomly divided into zinc-base montmorillonite and ca-montmorillonite intact skin group, zinc-base montmorillonite and calcium Ji Mengtuo
Stone damaged skin group, solvent intact skin group, solvent damaged skin group, every group 4.The tested preceding 24h backs of animal are with 6%
Na2S unhairings, remove gross area 80cm2.Check whether unhairing area skin is damaged because of unhairing before administration, compromised skin should not be finished
The toxicity test of whole skin.Damaged skin group modeling is carried out before experiment.After rabbit skin degerming sterile surgical knife will be used to make
" well " font scratches epidermis, slight oozing of blood occurs as degree using skin.Zinc-base montmorillonite and ca-montmorillonite are direct external application, solvent
Rabbit skin of unhairing uniformly is applied to, area is about 70cm2, uniformly smeared again after slightly dry 1 time (about 8mL altogether twice).Multiply it is wet with
Nonirritant gauze is fixed, and, coated with polyethylene film, fixation is then wrapped up again thereon, to prevent from evaporating.To tested material
24h is poisoned to death without rabbit afterwards, and the tested material for residuing in skin is washed away with warm water, cotton swab, continues to observe, continuous 7d.Observer
Rabbit death condition and systemic toxicity profiles performance, the i.e. diet of close observation rabbit, activity, fur, excrement and mouth, eye, nasal discharge
Deng reaction.Air embolism puts to death rabbit after 7 days, visually observes the internal organs such as its liver, lung, kidney, stomach, intestines.
(2) result
In skin sensibiligen experimentation, rabbit is without death, diet, activity, fur, excrement and mouth, eye, nose secretion
Thing etc. is without exception.Intact skin reacts：To wiping out back wool fermentation product as 6cm × 6cm rabbit, the external application zinc-base in 24h
Montmorillonite is administered with ca-montmorillonite, rabbit appetite, spirit and excrement no abnormality seen, also has no dead.After drug withdrawal in 7 days also not
See animal dead and other Novel presentations.
Damaged skin reacts：Wipe out the skin of back hair to rabbit to be abraded to oozing of blood with sand paper, external application zinc-base in 24h
Montmorillonite and ca-montmorillonite, rabbit appetite, spirit and excrement no abnormality seen in administration time, have no diseased organ, also have no
It is dead.That is zinc-base montmorillonite and diet, defecation, hair color, breathing, motion, skin and examination in 7 days after ca-montmorillonite topical administration
Test part and be showed no abnormal response.
(3) conclusion
Skin sensibiligen experiment show zinc-base montmorillonite and ca-montmorillonite do not cause rabbit local skin toxicity and
Systemic acute toxi-city reacts, and prompts zinc-base montmorillonite to have no that overt toxicity reacts to rabbit damaged skin with ca-montmorillonite.
Experimental example 8：Zinc-base montmorillonite is tested with ca-montmorillonite prescription proportion research
The present invention is tested by the clotting time, when comparing the blood coagulation of the zinc-base montmorillonite proportioning different from ca-montmorillonite
Between and the bleeding time, so as to investigate zinc-base montmorillonite and ca-montmorillonite proportioning prescription.
The preparation of zinc-base montmorillonite and ca-montmorillonite suspension：By the zinc-base montmorillonite and ca-montmorillonite of different proportion
Mixture, it is separately added into beaker, according to zinc-base montmorillonite and ca-montmorillonite mixture:Purified water=1:10 (mass ratioes),
Ultrasonication is carried out at room temperature, and the zinc-base montmorillonite and ca-montmorillonite suspension of different proportion is made, it is standby.
18~22g mouse 48 are taken, male and female are regardless of 24h fasting for solids and liquids.Pluck eyeball and take blood 1mL, be put into added with 0.1mL lemons
In the centrifuge tube of lemon acid sodium solution (38mg/mL), 10min is centrifuged with 1000r/min after mixing, 1, internal diameter 8mm test tubes is taken, adds
Enter pooled plasma and each 80mL of physiological saline, be put into warm bath 2min in 37 DEG C of water-baths immediately, then add 80mL different proportion zinc
Base montmorillonite and ca-montmorillonite suspension (2.8mg/mL), are placed into 37 DEG C of water-baths, timing immediately after mixing, and record adds certainly
To fibrin formation, the motionless required time of liquid level, as zinc-base montmorillonite and the multiple calcium of ca-montmorillonite suspension blood plasma after medicine
Time.It the results are shown in Table 12.
The zinc-base montmorillonite of table 12 and influence of the ca-montmorillonite different ratio to blood plasma recalcification time
Note：Analyzed from table, but it is 422s, the p ＜ compared with experimental example 2,3,4,5,6,7 to test 1 blood plasma recalcification time
0.05.It is 312s to test 7 blood plasma recalcification times；The p ＞ 0.05 compared with experimental example 2,3,4,5,6.From economic interests and clinical effect
Fruit considers, according to above experimental result, prescription selection of the present invention；Zinc-base montmorillonite:Ca-montmorillonite=5:8、7:9、8:10、9:
11、10:12 (mass percents)；Optimizing prescriptions：Zinc-base montmorillonite:Ca-montmorillonite is 5:8、7:9、8:10 (quality percentages
Than).
Experimental example 9：Zinc-base montmorillonite and the external blood coagulation research experiment of ca-montmorillonite
1 materials and methods
1.1 medicines and reagent：Zinc-base montmorillonite and the sterile styptic powder of ca-montmorillonite (prepared by embodiment 1)；Yunnan Baiyao
(Yunnan Paiyao Group Corp., Ltd)；Starch (Hunan Er-kang Pharmaceutical Co., Ltd.)；
1.2 experimental animal：Healthy adult new zealand white rabbit, 2.0~2.5kg of body weight, male and female dual-purpose (regular grade, Shandong
University's Experimental Animal Center provides)；
2 methods
The measure in external clotting time：32, test tube is taken, empirically medicine is divided into 4 groups：Blank group, starch group, the positive are right
Any medicine is not added with according to Yunnan Baiyao group and zinc-base montmorillonite and the sterile styptic powder group of ca-montmorillonite, every group of 8 test tubes, blank group
Thing, other components do not add each 100mg of different pharmaceutical.Choose healthy new zealand white rabbit 8, male and female half and half.Animal adaptability
Tested after raising 1 week, heart extracting blood after rabbit is fixed, every 8m1.Rapid injecting tube after blood is taken, every 2ml, is stood
Shake up, while timing starts, and test tube is gently tilted 1 time every 15S, observation whether there is blood coagulation appearance, until blood is not in test tube
Untill flowing again, i.e. the complete setting time of blood (S).It the results are shown in Table 13；
Table 13 to the new zealand white rabbit external clotting time influence (N=8)
Experimental result is evaluated：Zinc-base montmorillonite and the sterile styptic powder group of ca-montmorillonite P ＜ 0.01 compared with blank group；With
Starch group compares P ＜ 0.01；The P ＜ 0.05 compared with Yunnan Baiyao group.
3 results：Although there is shortening in starch group clotting time compared with blank group, but there was no significant difference (P ＞ 0.05).Cloud
Southern baiyao group is compared with blank group；There is obvious shortening clotting time (P ＜ 0.O1).Zinc-base montmorillonite is sterile only with ca-montmorillonite
Blood dissipates group and starch group ratio；There is clearly shortening (P ＜ 0.O1) in the external clotting time.Compared with positive drug Yunnan Baiyao, only
Blood material zinc-base montmorillonite and the sterile external coagulating effectiveness of styptic powder group of ca-montmorillonite are preferable, statistically significant (P ＜
0.O5).Result of the test illustrates that zinc-base montmorillonite and the sterile styptic powder of ca-montmorillonite have preferable external coagulating effectiveness.
Experimental example 10：Zinc-base montmorillonite and the research experiment of the sterile styptic powder anastalsis of ca-montmorillonite
1st, experiment material
1.1 Ba-Ma mini pigs, 22~30kg of body weight, male and female dual-purpose, regular grade, carried by the newborn pig farm of China of Rushan, Shandong Province city
For；
1.2 zinc-base montmorillonites are prepared with the sterile styptic powder of ca-montmorillonite by embodiment 1；
2nd, method and result
The research of 2.1 pairs of Ba-Ma mini pig femoral vein, artery trauma haemostatic effect, from healthy Ba-Ma mini pig 18,
Male and female half and half, random point 3 groups, every group 6, i.e. negative control starch group, positive control Yunnan Baiyao group, zinc-base montmorillonite and calcium
The sterile styptic powder group of base montmorillonite.
1. experimental animal Ba-Ma mini pig establishes vascular trauma model, sodium phenobarbital auricular vein anesthesia (30mg/
kg)；Face upward position to be fixed on operating table, sterilization, fully exposure and free femoral vein about 6cm, it is quiet to clamp proximal part stock with artery clamp
Arteries and veins, the other end are lifted with rope, and exposure is punctured using medical arterial duct puncture sheath (diameter 0.3cm) in femoral vein middle part
Good femoral vein, after model is established, blood sprays from puncturing hole after decontroling artery clamp, immediately to bleeding surface of a wound pressing haemostatic bag
(each bleeding surface of a wound uses 30g subject materials：Negative control starch, positive control Yunnan Baiyao, trial drug zinc-base cover de-
Stone and the sterile styptic powder of ca-montmorillonite, (the hemostasis bag) being made into are stopped blooding, and after pressing 2min, observe and record each group animal
The haemostatic effect of the surface of a wound.
2. establishing femoral artery Hemorrhage Model in hind leg opposite side in the same way, pressing starts simultaneously at timing, presses
A bleeding part is observed every 30s after 2min, stops timing, i.e. bleeding time when loseing oozing of blood to 5s.Observe and record each group
The haemostatic effect of the animal surface of a wound.During pressing bleeding part, artery surface of a wound bleeding is attracted in hemostasis bag, hemostasis bag pressing
It is preceding first to use scales/electronic balance weighing, weight is recorded, the weight in wet base for claiming hemostasis to wrap after hemostasis again, before subtracting hemostasis with the weight after hemostasis
Weight, you can represent the amount of bleeding.
3. observation terminates rear layer-by-layer suture peritonaeum, muscle, skin, and is sprinkled with PVP-I on suture surface to prevent from feeling
Dye, experimentation pay attention to sterile working.If failing to control femoral artery bleeding not reapply other intervening measures, record in 24h and move
Thing death toll, and femoral artery wound tissue is removed in time；Survive experimental animal, postoperative free water, diet, in Post operation 24h
The Observation of Anesthesia femoral artery surface of a wound, removes femoral artery wound tissue, is fixed with 10% neutral formalin, FFPE, does histotomy,
HE dyeing observation wound tissue pathological change situations.
2.2 statistical procedures experimental datas withRepresent, with SPSS13.0 softwares, entered using one-way analysis of variance
Row statistical procedures, inspection is used to the enumeration data of Non-Gaussian Distribution.Significance P ＜ 0.O5.
The influence of 2.3 pairs of Ba-Ma mini pig femoral vein wound hemostasis effects
In the experiment of Ba-Ma mini pig femoral vein wound hemostasis, can not effectively it stop after negative control starch pressing 2min
Blood, there is obvious oozing of blood；Wherein there is an animal wound to have oozing of blood after positive control Yunnan Baiyao pressing 2min, hemostasis is effectively
Rate 85.6%；Can effectively it stop blooding after zinc-base montmorillonite styptic powder hemostasis bag pressing 2min sterile with ca-montmorillonite.With shallow lake
Powder control group compares, and positive control Yunnan Baiyao and zinc-base montmorillonite styptic powder hemostasis bag sterile with ca-montmorillonite are to Ba Ma little
The anastalsis of type pig femoral vein traumatic bleeding has significant difference (P ＜ 0.O5, P ＜ 0.O1).It is shown in Table 14.
Influence (n=6) of the table 14 to Ba-Ma mini pig femoral vein wound hemostasis effect
1P ＜ 0.05,2P ＜ 0.01, compared with starch group.
The influence of 2.4 pairs of Ba-Ma mini pig femoral artery wound hemostasis effects
Ba-Ma mini pig femoral artery wound hemostasis result of the test is shown, compared with starch control group, Yunnan Baiyao group and zinc
Base montmorillonite can significantly shorten Ba-Ma mini pig femoral artery bleeding time (P ＜ with the sterile styptic powder group of ca-montmorillonite
0.O1), and amount of bleeding (P ＜ 0.O5, P ＜ 0.O1) is reduced.Zinc-base montmorillonite is with the sterile styptic powder group of ca-montmorillonite to a bar horse
Miniature pig femoral artery wound hemostasis effect will be significantly better than Yunnan Baiyao group, and the bleeding time, which has, significantly shortens (P ＜ 0.O5), bleeding
Amount also significantly reduces (P ＜ 0.O5).The styptic powder hemostasis bag pressing sterile with ca-montmorillonite of tested hemostatic material zinc-base montmorillonite
Can effectively it stop blooding after about 5min；Negative control starch group does not take other measures, wherein has 2 bars of horses small-sized in 24h
Pig shock property caused by excessive blood loss is dead.It the results are shown in Table 15.
Table 15 to Ba-Ma mini pig femoral artery wound hemostasis effect influence (N=6)
1P ＜ 0.05,2P ＜ 0.01, compared with starch group；3P ＜ 0.05, compared with Yunnan Baiyao group.
Experiment shows that zinc-base montmorillonite styptic powder hemostasis bag sterile with ca-montmorillonite is to Ba-Ma mini pig stock artery and vein
Fatal hemorrhage model has significant haemostatic effect, reduces the death rate.
It is visible in micro- Microscopic observation after the pathological observation histotomy HE dyeing at 2.5 femoral hemostasis positions, it is tested to stop
Blood material starch group, Yunnan Baiyao group and zinc-base montmorillonite and the sterile styptic powder group of ca-montmorillonite, each group blood vessel surface of a wound and attached
Near to find no the change such as irregular thickening, ulcer, necrosis or Aneurysmformation of vascular wall, each group pathological examination is without obvious
Abnormal change, but the thrombus that each group has blood vessel Cavity surface adheres to, and is mainly shown as that fresh thrombus is formed under its corresponding microscope.
Pathological observation result is as follows；
A, the starch group femoral artery blood vessel surface of a wound, irregular thickening, ulcer, necrosis or the aneurysm shape of vascular wall are found no
Change into waiting；
B, starch group femoral artery blood vessel Cavity surface has thrombus attachment；
C, the Yunnan Baiyao group femoral artery blood vessel surface of a wound, irregular thickening, ulcer, necrosis or the artery of vascular wall are found no
Neoplasia etc. changes；
D, Yunnan Baiyao group femoral artery blood vessel Cavity surface has fresh thrombosis；
E, zinc-base montmorillonite and the sterile styptic powder group femoral artery blood vessel surface of a wound of ca-montmorillonite, find no vascular wall not
Rule thickens, ulcer, necrosis or Aneurysmformation etc. change；
F, zinc-base montmorillonite has thrombus attachment with the sterile styptic powder group femoral artery blood vessel Cavity surface of ca-montmorillonite.
This experiment passes through real to the external blood coagulation of new zealand white rabbit, Ba-Ma mini pig mortality stock artery and vein wound hemostasis
The observation tested, it was demonstrated that zinc-base montmorillonite of the present invention has preferable haemostatic effect with ca-montmorillonite sterile styptic powder, can
Fast and effectively stop blooding；Traumatic bleeding is simulated by animal experimental model, as a result finds to cover using zinc-base montmorillonite and calcium base
The de- sterile styptic powder progress first aid haemostatic effect of stone is very notable, for zinc-base montmorillonite with the sterile styptic powder of ca-montmorillonite in urgency
The application for rescuing aspect provides reliable experimental basis.Traditional Hemostasis such as pressurizes, dressing filling and tourniquet, is all
Stopped blooding by pressure, tourniquet hemostasis can also cause remote organization's ischemic and metabolic disorder to cause serious complication etc..Zinc-base
Montmorillonite is used as a kind of external application first aid hemostatic material with ca-montmorillonite styptic powder hemostasis bag, price definite with haemostatic effect
Many advantages, such as cheap, carrying portable, easy to use, safety durable, Great vessel trauma bleeding can effectively be stopped blooding, meet weight
Hinder first aid " save one's life, be delayed " needs, and have concurrently it is light, do not generate heat, the characteristics of being easy to debridement.
The features of the present invention and have the beneficial effect that：
1st, the zinc-base montmorillonite described in present invention application and the sterile styptic powder active ingredient zinc-base of ca-montmorillonite cover de-
Stone, ca-montmorillonite are a kind of safe and non-toxic medicines, after medication, are not less readily available for absorption by the skin, and do not enter blood circulation, and are covered de-
Stone is partially formed elecrtonegativity, and then positively charged, distribution of charges are in polymorphic micro phase separation structure between layers.So, by quiet
Electro ultrafiltration, montmorillonite can produce interaction with charging property biomolecule and bacterium, virus, toxin, be fixed, remove；Reach
To corruption of dispelling, myogenic, promote ulcer healing.
2nd, the preparation described in present invention application is administered by external preparation for skin approach, has antibacterial, drying and dehydrating, and suppression blood is made
With.Zinc-base montmorillonite has with the montmorillonite that ca-montmorillonite dissociates to be acted on compared with strong absorptive, is reduced tissue fluid and is oozed out, the surface of a wound
Dry, topical wounds oedema degree can be mitigated, accelerate granulation tissue generation, healing acceleration, the purpose for restraining myogenic can be reached.Cover
De- stone is immediately directed against bacterium surface so as to play the bacteriostasis of long period, is characterized in that antibacterial power is strong, tasteless, performance is steady
It is fixed, nonirritant, non-toxic, bacterium, virus, fungi, gemma and protozoon etc. can be suppressed, should to the noiseless effect of wound healing
With surpassing other any Wound care products.
3rd, the preparation described in present invention application, the zinc ion that wherein zinc-base montmorillonite dissociates can strengthen phagocyte and gulp down
Function, chemotactic vigor and sterilizing function are bitten, and the Free Radical Level in phagocyte is kept by superoxide dismutase, is sent out
Wave bactericidal action, the healing of acceleration of wound, burn；Other zinc ion energy precipitating proteins, external application have convergence antisepsis, help
Granulation tissue is formed；Zinc also has the function that to eliminate oxygen radical, is the factor for adjusting inflammatory cell activity.It also suppresses to have children outside the state plan
The external bacterium of concentration is managed to increase；And montmorillonite has the functions such as hemostasia and detumescence, eliminating inflammation and expelling toxin, convergence myogenic simultaneously.
4th, the present invention application described in preparation, the calcium ion that wherein ca-montmorillonite dissociates can shorten the bleeding time and
Blood plasma recalcification time.
In summary, application of the present invention, preparation use zinc-base montmorillonite, ca-montmorillonite as medicine of the present invention
Active ingredient, with pharmaceutic adjuvant, medicament is made by the technique such as high temperature hot air sterilization, mixing, aseptic subpackaged.By external preparation for skin
Approach is administered, and rapid blood coagulation and can stop blooding, and can prevent wound infection.
Brief description of the drawings
Fig. 1 be zinc-base montmorillonite dry heat temperature at 170~180 DEG C, the xeothermic time is in 180~240min, X-ray diffraction
Collection of illustrative plates, abscissa are 2 θ (°), and ordinate is intensity (arbitrary unit)；
Fig. 2 is ca-montmorillonite dry heat temperature at 250~300 DEG C, the xeothermic time in 120min, X-ray diffracting spectrum,
Abscissa is 2 θ (°), and ordinate is intensity (arbitrary unit)；
Fig. 3 is that the sample zinc ion Cumulative release amount (%) of embodiment 1,2,3 makees curve map, and abscissa is the time, ordinate
For release；
Fig. 4 is that the sample calcium ion Cumulative release amount (%) of embodiment 1,2,3 makees curve map, and abscissa is the time, ordinate
For release.
Embodiment
With reference to embodiment, the present invention is described further, but not limited to this.
The supplementary material explanation of embodiment 1~3：
| Supplementary material title | Manufacturing enterprise | Execution standard |
| Zinc-base montmorillonite | Shandong Sibangde Pharmaceutical Co., Ltd. | Company standard |
| Ca-montmorillonite | Shandong Sibangde Pharmaceutical Co., Ltd. | Two addendums of Chinese Pharmacopoeia 2010 edition |
Involved device and equipment are powder production common apparatus in embodiment, and market is commercially available.It is described as follows：
Dry heat sterilization cabinet (model HDA500) yangtze river in nanjing Yao Ji Manufacturing Co., Ltds are on sale；Grow in batch mixer (100L) Nanjing
Jiang Yao machines Manufacturing Co., Ltd is on sale.
Embodiment 1, zinc-base montmorillonite and the sterile styptic powder of ca-montmorillonite and preparation method
1st, raw and auxiliary material inventory proportioning (w/w):
8 parts of zinc-base montmorillonite
10 parts of ca-montmorillonite；
2nd, prepare
(1) the zinc-base montmorillonite of formula ratio is put into dry heat sterilization cabinet, temperature is 170~180 DEG C and sterilized, sterilization time
For 180min, it is standby to be down to room temperature；
(2) ca-montmorillonite of formula ratio is put into dry heat sterilization cabinet, temperature is 250~300 DEG C and sterilized, sterilization time
For 120min, it is standby to be down to room temperature；
(3) material for obtaining step (1), step (2) is put into sterilized mixing tank；It is stirred and is well mixed
Afterwards；It is aseptic subpackaged to produce zinc-base montmorillonite and the sterile styptic powder of ca-montmorillonite.
Embodiment 2, zinc-base montmorillonite and the sterile styptic powder of ca-montmorillonite and preparation method
1st, raw and auxiliary material inventory proportioning (w/w):
7 parts of zinc-base montmorillonite
9 parts of ca-montmorillonite；
2nd, prepare
(1) the zinc-base montmorillonite of formula ratio is put into dry heat sterilization cabinet, temperature is 170~180 DEG C and sterilized, sterilization time
For 240min, it is standby to be down to room temperature；
(2) ca-montmorillonite of formula ratio is put into dry heat sterilization cabinet, temperature is 250~300 DEG C and sterilized, sterilization time
For 120min, it is standby to be down to room temperature；
(3) material for obtaining step (1), step (2) is put into sterilized mixing tank；It is stirred and is well mixed
Afterwards；It is aseptic subpackaged to produce zinc-base montmorillonite and the sterile styptic powder of ca-montmorillonite.
Embodiment 3, zinc-base montmorillonite and the sterile styptic powder of ca-montmorillonite and preparation method
1st, raw and auxiliary material inventory proportioning (w/w):
5 parts of zinc-base montmorillonite
8 parts of ca-montmorillonite；
2nd, prepare
(1) the zinc-base montmorillonite of formula ratio is put into dry heat sterilization cabinet, temperature is 170~180 DEG C and sterilized, sterilization time
For 210min, it is standby to be down to room temperature；
(2) ca-montmorillonite of formula ratio is put into dry heat sterilization cabinet, temperature is 250~300 DEG C and sterilized, sterilization time
For 120min, it is standby to be down to room temperature；
(3) material for obtaining step (1), step (2) is put into sterilized mixing tank；It is stirred and is well mixed
Afterwards；It is aseptic subpackaged to produce zinc-base montmorillonite and the sterile styptic powder of ca-montmorillonite.
Claims (8)
1. a kind of zinc-base montmorillonite and application of the sterile styptic powder of ca-montmorillonite in the medicine of skin wound healing is prepared, institute
Zinc-base montmorillonite and the sterile styptic powder of ca-montmorillonite are stated, is made up of following raw material by mass parts：
5~10 parts of zinc-base montmorillonite
8~12 parts of ca-montmorillonite；
Wherein described zinc-base montmorillonite, ca-montmorillonite, crushed 500 mesh sieves；
Described zinc-base montmorillonite is after montmorillonite is acidified, and is soaked or eluted with water-soluble zinc salt solution and dried, and crushed
Cross 500 mesh sieves to obtain, zinc ion therein is zinc-base montmorillonite labelled amount 5.0~9.5%；
Described ca-montmorillonite is after montmorillonite is acidified, and is soaked or eluted with water-soluble calcium salting liquid and dried, and crushed
Cross 500 mesh sieves to obtain, calcium ion therein is ca-montmorillonite labelled amount 5.0~9.5%.
2. zinc-base montmorillonite as claimed in claim 1 is preparing the medicine of skin wound healing with the sterile styptic powder of ca-montmorillonite
Application in thing, it is characterised in that the application is zinc-base montmorillonite be used alone with the sterile styptic powder of ca-montmorillonite or
With other medicines with the use of the use in conjunction as medicament.
3. zinc-base montmorillonite as claimed in claim 1 is preparing the medicine of skin wound healing with the sterile styptic powder of ca-montmorillonite
Application in thing, it is characterised in that the skin trauma includes skin tears bleeding, scald, injury from falling down.
4. zinc-base montmorillonite as claimed in claim 1 is preparing the medicine of skin wound healing with the sterile styptic powder of ca-montmorillonite
Application in thing, it is characterised in that the zinc-base montmorillonite and the sterile styptic powder of ca-montmorillonite, mass parts are pressed by following raw material
It is made：
5~8 parts of zinc-base montmorillonite
8~10 parts of ca-montmorillonite.
5. zinc-base montmorillonite as claimed in claim 4 is preparing the medicine of skin wound healing with the sterile styptic powder of ca-montmorillonite
Application in thing, it is characterised in that the zinc-base montmorillonite and the sterile styptic powder of ca-montmorillonite, mass parts are pressed by following raw material
It is made：
8 parts of zinc-base montmorillonite
10 parts of ca-montmorillonite.
6. zinc-base montmorillonite as claimed in claim 4 is preparing the medicine of skin wound healing with the sterile styptic powder of ca-montmorillonite
Application in thing, it is characterised in that the zinc-base montmorillonite and the sterile styptic powder of ca-montmorillonite, mass parts are pressed by following raw material
It is made：
7 parts of zinc-base montmorillonite
9 parts of ca-montmorillonite.
7. zinc-base montmorillonite as claimed in claim 4 is preparing the medicine of skin wound healing with the sterile styptic powder of ca-montmorillonite
Application in thing, it is characterised in that the zinc-base montmorillonite and the sterile styptic powder of ca-montmorillonite, mass parts are pressed by following raw material
It is made：
5 parts of zinc-base montmorillonite
8 parts of ca-montmorillonite.
8. the zinc-base montmorillonite as described in claim 4~7 is any is preparing skin trauma with the sterile styptic powder of ca-montmorillonite
Application in the medicine of healing, it is characterised in that wherein described zinc-base montmorillonite and the sterile styptic powder of ca-montmorillonite press with
Lower section method is made：
(1) the zinc-base montmorillonite of formula ratio is crushed, crosses 500 mesh sieves, be put into dry heat sterilization cabinet, temperature is 170~180 DEG C and gone out
Bacterium, sterilization time are 180~240min, and it is standby to be down to room temperature；
(2) ca-montmorillonite of formula ratio is crushed, crosses 500 mesh sieves, be put into dry heat sterilization cabinet, temperature is 250~300 DEG C and gone out
Bacterium, sterilization time 120min, it is standby to be down to room temperature；
(3) material for obtaining step (1), step (2) is put into sterilized mixing tank；After being stirred and being well mixed；
It is aseptic subpackaged to produce zinc-base montmorillonite and the sterile styptic powder of ca-montmorillonite.
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| CN201510514239.5A CN105030824B (en) | 2015-08-20 | 2015-08-20 | A kind of application of zinc-base montmorillonite and the sterile styptic powder of ca-montmorillonite |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1957948A (en) * | 2005-11-04 | 2007-05-09 | 浙江海力生制药有限公司 | Modified montmorillonite, preparation method and application |
| CN101773518A (en) * | 2010-02-24 | 2010-07-14 | 济南康众医药科技开发有限公司 | Medicine for treating infectious diseases |
| CN102058898A (en) * | 2011-01-13 | 2011-05-18 | 深圳市源兴纳米医药科技有限公司 | Powder with antibacterial and haemostatic effects and preparation method and applications thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| US20120058165A1 (en) * | 2010-08-30 | 2012-03-08 | Thomas James Klofta | Opacifying Lotion |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1957948A (en) * | 2005-11-04 | 2007-05-09 | 浙江海力生制药有限公司 | Modified montmorillonite, preparation method and application |
| CN101773518A (en) * | 2010-02-24 | 2010-07-14 | 济南康众医药科技开发有限公司 | Medicine for treating infectious diseases |
| CN102058898A (en) * | 2011-01-13 | 2011-05-18 | 深圳市源兴纳米医药科技有限公司 | Powder with antibacterial and haemostatic effects and preparation method and applications thereof |
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| 矿物药剂蒙脱石的应用;王科研;《养殖技术顾问》;20100531;第165页 * |
| 联合用药治疗上消化道出血疗效观察;邱创衡;《药物与临床》;20120430;第19卷(第10期);第92-93页 * |
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