CN104758310B - Compound montmorillonite sucrose ointment and its preparation method and application - Google Patents
Compound montmorillonite sucrose ointment and its preparation method and application Download PDFInfo
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Abstract
The present invention relates to a kind of compound montmorillonite sucrose ointment and its preparation method and application for treating skin ulcer.The ointment is made of following raw material by mass parts：50~80 parts of montmorillonite, 410~656 parts of sucrose, 5~7 parts of Macrogol 6000,5~7 parts of glycerine, 10~16 parts of sorbierite, 5~7 parts of sodium alginate, 600~900 parts of sterile water.It uses montmorillonite, sucrose for the active ingredient of drug of the present invention and pharmaceutic adjuvant, medicament is made by techniques such as moist heat sterilization, dissolving, low speed homogeneous, high speed homogenization, stirring, cooling, sterile fillings.The present invention also provides said preparations to prepare the application in treating skin ulcer drug.By external preparation for skin drug administration, all there is preferable effect to the skin ulcer of different times.
Description
Technical field
The present invention relates to a kind of pharmaceutical compositions and its preparation method and application, are related to a kind of compound for treating skin ulcer
Montmorillonite sucrose ointment and its preparation method and application, belongs to pharmaceutical technology field.
Background technology
Chronic ulcer of skin is changeable a kind of high illness rate, high treatment cost, clinical setting, prognosis mala, it is a variety of to see
One pathologic process of disease, basic characteristics are skin healing process stands idle in inflammation, proliferation, maturation and rebuild overlapped
Different phase.With the increase for entering aged society and diabetes number of patients.Chronic ulcer of skin is increasingly becoming one clinical
Common disease, frequently-occurring disease, increase society, financial burden, and clinical treatment is very intractable.
Skin ulcer by different pathogenic factors can be divided into wound infection, pressure ulcer, venous ulcer, diabetes burst
Ulcer etc..In terms of generation crowd, the body surface chronic wounds caused by wound are based on 2O~5O Sui the young and the middle aged；Glycosuria
Characteristic of disease, repressive and venous ulcer are based on 6O years old or more the elderly.Body surface chronic wounds mechanism is complicated,
So far it not yet illustrates completely.The cause of disease is different, and mechanism is also different.The treatment of body surface chronic wounds very spine
Hand, since teiology and pathogenesis are not exactly the same, the mode for the treatment of, there are larger differences for method.In principle, first
Local treatment obeyed systemic therapy before this, and Wound treatment is served in teiology treatment.As diabetic ulcer treatment must be controlled first
Blood glucose processed；Varicose ulcer of lower extremity must handle the problem of varication itself etc. first.Secondly, the surgery processing of the surface of a wound
(such as local debridement and anti-infective) should be basis and the premise of local treatment, because slough is retained and infected
The surface of a wound is impossible to reach quickly to heal.Again, using certain measures and method come wound healing.
Bedsore is to lead to histocyte hypoxic-ischemic, nutrition due to local soft tissue continuous compression, hemodynamic change
Dysbolism and degeneration necrosis occurs.Bedsore is that a kind of serious complication not only increases pain once bedsore occurs to patient
Hardship, aggravate the state of an illness, extend the course of disease, when serious can due to secondary infection causes septicemia threat to life.Bedsore lesion starts
Epidermis injury, the extensive destruction that erythema is presented, then develops into the deep tissues such as skin, subcutaneous tissue, muscle and bone, seriously
Person can secondary infection, cause septicemia and cause patient dead.
Treatment skin ulcer bedsore disease is divided into because of processing, local treatment, operative treatment, supportive treatment, medicine at present
Object therapy etc..Local treatment can be divided into physiotherapy and drug therapy.
The physiotherapy clinically used has：Special electromagnetic therapeutic apparatus radiation therapy, high-frequency treatment and direct current electron ion
Importing, the local irradiation of WP broad-spectrum therapeutic instrument, thermal current instrument blow roasting, oxygen air blowing therapy etc..Physical therapy be suitable for clinically I~
The treatment of II phase bedsore.Its effect have detumescence, anti-inflammatory analgetic improve bedsore local blood microcirculation, promote section reparation with again
Raw, control anaerobic bacteria accelerates surface of a wound drying, improves tissue oxygen content, to accelerate bedsore to heal.Regional is clinically
Anti-inflammatory, germ killing drugs are mostly used, such as：Phenytoinum naticum, Ciprofloxacin Hydrochloride, high pristinamycin, Radix Arnebiae extract etc..The effect of its drug
Mechanism is：Phenytoinum naticum-can promote the proliferation of fibrocyte and the precipitation of collagen, and secretion is made to significantly reduce, and stimulate fresh granulation
It organizes to grow to surface.Ciprofloxacin Hydrochloride-has stronger bactericidal effect to bedsore pathogenic bacteria, can quickly and effectively control sore
It infects in face.High pristinamycin-aluminium ion and micro mercury ion act on bed sore surface, and energy absorbing toxin makes mycoprotein precipitate
Solidification, plays restraining and sterilizing bacteria, and can absorb the sepage of wound surface, promotees its drying, promotes ulcer surface incrustation healing.Asian puccoon carries
Take object-that there is heat clearing and blood circulation promoting, putrefaction-removing granulation-promoting, convergence analgesic；Be conducive to regeneration and the healing of sore face.
To sum up, traditional treatment methods skin ulcer bedsore is clinically generally used at present, as keeps wound as much as possible
Dry mouth absorbs and excludes wound exudate, but there is also defects for these methods, and wound can be made de- to prevent bacterium infection
Water, incrustation are mixed with some epidermal cells in crust, these cells are forced toward depths under dry crust, to extend cotton-padded mattress
The agglutination of sore.
In short, the above therapy all has different degrees of defect, clinical application is made to be very limited.It is wide to meet
The clinical demand of big patient, therefore, those skilled in the art are seeking always one kind for many years can develop safe height
Effect, the external used medicine for the treatment of skin ulcer easy to use, i.e. compound montmorillonite sucrose external use sterile ointment, with abundant clinical use
Medicine.In addition, be exclusively used in treatment skin ulcer montmorillonite external used medicine there is not been reported.
Invention content
In view of the deficiencies of the prior art, the present invention provides a kind of compound montmorillonite sucrose ointment for treating skin ulcer, originally
Invention also provides the preparation method and application of the ointment.
Term explanation：
Skin ulcer of the present invention, refer to decubitus ulcer, scald ulcer, calf ulcer, ulcer after with shape blebs,
Diabetic ulcer, postoperative ulcer.
Room temperature：Refer to the environment temperature residing for experimental implementation, controls within the scope of 15~30 DEG C.
The invention is realized by the following technical scheme：
A kind of compound montmorillonite sucrose ointment for treating skin ulcer, is made of following raw material by mass parts：
According to the present invention, preferably；
A kind of compound montmorillonite sucrose ointment for treating skin ulcer, is made of following raw material by mass parts：
According to the present invention, further preferred；
A kind of compound montmorillonite sucrose ointment for treating skin ulcer, is made of following raw material by mass parts：
Alternatively, a kind of compound montmorillonite sucrose ointment for treating skin ulcer, is made of following raw material by mass parts：
Alternatively, a kind of compound montmorillonite sucrose ointment for treating skin ulcer, is made of following raw material by mass parts：
Compound montmorillonite sucrose ointment of the present invention, wherein the montmorillonite is medicinal smectite, institute of the present invention
The supplementary material that uses it is not specified be regular market purchase product.
According to the present invention, the preparation method of the compound montmorillonite sucrose ointment formulation includes the following steps：
(1) montmorillonite, sucrose, Macrogol 6000, glycerine, sorbierite, sodium alginate, spare is weighed according to the ratio；
(2) montmorillonite, sucrose, Macrogol 6000, glycerine, sorbierite, sodium alginate, sterile water are put into dissolving tank
In, it opens and stirs and heat up, be continuously heating to 135 DEG C, sterilizing, the retention time is in 60min；Then after being cooled to 80~90 DEG C,
It keeps the temperature spare；
(3) it by step (2) resulting material, aseptically, is pumped into shearing tank；Under the conditions of 65~70 DEG C of temperature,
It opens 1800~2000r/min of cutter low speed to shear 4~5 minutes, then 2~3 points of 3000~3200r/min of high speed shearings
Clock；Close cutter, open stirring, rotating speed be 100~110r/min, continue stirring 2~4 minutes, then again rotating speed be 60
~80r/min is stirred, and stops stirring when being cooled to 30~35 DEG C, compound montmorillonite sucrose ointment formulation product is made；
(4) it packs, examines, storage.
In method made above, it is preferred that the pipeline of be useful for material conveying first passes through sterilization treatment in advance.It prepares
Equipment used in method is according to the prior art.
The present invention also provides application of the compound montmorillonite sucrose ointment in the drug for preparing treatment skin ulcer.Described
Skin ulcer, including decubitus ulcer, scald ulcer, calf ulcer, ulcer after with shape blebs, diabetic ulcer, postoperative burst
Ulcer.
Compound montmorillonite sucrose ointment quality standard prepared by the present invention is as follows but unlimited compound as described below is covered and taken off
Stone sucrose ointment standard.
Compound montmorillonite sucrose ointment
This product should be the 96.0%~110.0% of labelled amount containing montmorillonite；Containing sucrose should be labelled amount 95.0%~
110.0%
【Character】Compound montmorillonite sucrose ointment is off-white color ointment；
【Differentiate】
1,4g compound montmorillonite sucrose ointments are taken, after adding water 50ml to stir, filtering takes filter cake to be rushed repeatedly with 300ml water
It washes three times, takes filter cake to be dried at 105 DEG C, montmorillonite obtained above is ground into fine powder；It takes fine powder appropriate, is placed on load sample frame,
By load sample frame be put into drier (contain saturated nacl aqueous solution, at 20 DEG C relative humidity about 75%) in taken out after about 12 hours, will
Sample on load sample frame flattens, and is measured according to x-ray powder diffraction (two annex IX F of Chinese Pharmacopoeia version in 2010),
It is scanned in the range of 2 °~80 ° of the angle of diffraction (2 θ), montmorillonite X-ray diffracting spectrum.With montmorillonite standard items x-ray diffraction pattern
Montmorillonite characteristic peak (angle of diffraction (2 θ) respectively may be about 5.8 °, 19.8 ° and 61.9 °) in spectrum is consistent.
2, control sucrose product 10mg is taken, adds methanol solution 50ml, as a contrast product solution.It is another to take this product appropriate (about quite
In sucrose 10mg) plus methanol solution 50ml, filtering；Filtrate is as test solution.
Each 2 μ l of above-mentioned solution are taken respectively, are put on lamellae, are dried up immediately, with volume ratio 10:5:3:The 1 of 2,2-dichloros
Ethane:Glacial acetic acid:Methanol:Water mixed liquid is unfolded, until 15cm or so, takes out, high temperature drying.It is repeated once expansion, high temperature drying
Afterwards.Uniformly spraying thymol solution [takes thymol 0.5g to be dissolved in 100ml ethanol sulfuric acids mixed liquor (volume ratio 19:
1) it], heats 10 minutes for 130 DEG C.The color size of test solution major spot is consistent with reference substance solution.
【It checks】
Granularity shines version (Ⅸ E of annex) the first method inspection in 2010 of granularity and determination of particle size distribution Chinese Pharmacopoeia, must not
Particle of the detection more than 90 μm.
Viscosity takes this product, according to viscosimetry Chinese Pharmacopoeia version (VI G of annex) second method in 2010, is revolved using NDJ-1 types
Rotatable viscosmeter, with No. 4 rotors, rotating speed is 6 turns per minute, is measured in accordance with the law, the dynamic viscosity at 25 DEG C should be 50~
70Pa.s。
Inverted sugar contrast solution：Glucose 10mg is weighed, sets in 50ml measuring bottles, methanol solution is added to dissolve in right amount, first is used in combination
Alcoholic solution is diluted to scale, shake up to get.
Test solution：Sample 1.0g is weighed, it is accurately weighed, it sets in 50ml measuring bottles, adds methanol solution appropriate, filter；And
Be diluted to scale with methanol solution, shake up to get.
Each 2 μ l of above-mentioned solution are taken respectively, are put on silica gel g thin-layer plate, are dried up immediately, with volume ratio 10:5:3:The 1 of 2,
2-dichloroethanes:Glacial acetic acid:Methanol:Water mixed liquid is unfolded, until 15cm or so, takes out, high temperature drying.It is repeated once expansion, it is high
Temperature drying.Uniformly spraying thymol solution [takes thymol 0.5g to be dissolved in 100ml ethanol sulfuric acid mixed liquor (wherein second
Alcohol and sulfuric acid volume ratio are 19:1) it], heats 10 minutes for 130 DEG C.As a result：Test solution does not show spot at contrast solution spot
Point；Such as aobvious spot, the color of test solution spot must not be deeper than contrast solution spot colors (1.0%).
It is sterile to shine version (Ⅺ H of the annex) inspection in 2010 of Sterility Test Chinese Pharmacopoeia, regulation should be met.
Other should meet related items regulation Chinese Pharmacopoeia version two (I F of annex) in 2010 under ointment item.
【Assay】Smectite content takes 4g compound montmorillonite sucrose ointment, and after adding water 50ml stirring and dissolvings, filtering takes
Filter cake is flushed three times repeatedly with 1000ml water, take filter cake at 105 DEG C dry to constant weight to get test sample in contained montmorillonite weight
Amount, calculate to get.
Cane sugar content takes this product 1.4g, accurately weighed, sets in small beaker, adds appropriate amount of water, stirring and dissolving, after filtering；It is such as molten
Liquid is not clarified, and continues filtering until liquid is clarified；Transfer is set in 100ml measuring bottles, and is diluted with water to scale, is shaken up；It is accurate
1ml is measured, sets in 100ml measuring bottles, is diluted with water to scale, shake up, as test solution.Sucrose 12.5mg separately is taken, it is accurate
It is weighed, it sets in 250ml measuring bottles, adds water shaking dissolving, and be diluted with water to scale, shake up, as a contrast product solution.
Precision measures reference substance solution and each 1ml of test solution, sets respectively in 10ml measuring bottles, adds sulfuric acid solution 3ml molybdenums
Acid ammonium solution 3.5ml, and it is diluted with water to scale, it shakes up, in boiling water bath after 25 minutes, is water-cooled to room temperature.According to middle traditional Chinese medicines
Allusion quotation version two (IV A of annex) uv-spectrophotometric in 2010 measures at 700nm, and blank correction, records absorbance, calculates,
To obtain the final product.
Compound montmorillonite sucrose ointment of the present invention is that medicinal active ingredient is montmorillonite, sucrose and medicinal diluent
Or the pharmaceutical composition of carrier mixing, the form that the composition is administered through skin external used medicine, still to the bedsores of different times
Treatment to skin ulcer caused by diabetic complication, all showing it has hypertonic, sterilization, drying and dehydrating effect.Specifically
Feature is as follows：
1, it is externally applied to the surface of a wound using sucrose in invention formulation, forms hyperosmotic state outside edematous tissue, while can also put
Go out heat, changes local osmotic pressure, it is hypertonic also to inhibit bacterial growth to which excessive moisture in edematous tissue to be sucked out, also
It can play the role of a kind of " disinfection ", and use as hypertonic glucose dressing mechanism, because sucrose can mitigate with hypertonic effect
Topical wounds oedema degree accelerates granulation tissue to generate, healing acceleration, can achieve the purpose that restrain myogenic.
2, the acid-base property that can change wound in invention formulation using sucrose promotes epithelial cell to generate gentle and kindhearted physiology thorn
Swash, supply wound nutrition, keeps wound blood circulation nearby good, promote cytothesis, accelerate Wound healing.
3, montmorillonite is a kind of safe and non-toxic natural drug in invention formulation, after medication, is not less readily available for absorption by the skin, not into
Enter blood circulation, and montmorillonite is partially formed elecrtonegativity, and it is then positively charged between layers, and distribution of charges is in polymorphic microfacies point
From structure.In this way, by electrostatic interaction, montmorillonite can generate phase interaction with charging property biomolecule and bacterium, virus, toxin
With being fixed, remove；Reach corruption of dispelling, myogenic, promote ulcer healing.
4, montmorillonite and sucrose are used in combination in invention formulation, and montmorillonite has compared with strong absorptive effect, due to sugarcane
Excessive moisture in edematous tissue is oozed out in the hyperosmosis effect of sugar combination, sucrose, is sucked by montmorillonite, reduces tissue fluid and oozes
Go out, surface of a wound drying can mitigate topical wounds oedema degree, granulation tissue is accelerated to generate, and healing acceleration can reach convergence myogenic
Purpose.
5, montmorillonite combines sucrose therapy skin ulcer, plays synergistic effect.Its main feature is that antibacterial power is strong, tasteless, performance
It is stable, nonirritant, toxicity is low, can inhibit bacterium, virus, fungi, gemma and protozoon etc., to the noiseless effect of wound healing,
Using surpassing other any type Wound care products.The two use in conjunction is to promote the quick healing of bedsore.It is made into
Combined dosage form accords with the characteristics of the characteristics of drug medication and clinical treatment completely.
(bedsore scalds ulcer, diabetic keratopathy after ulcer, calf ulcer, with shape blebs to the treatment skin ulcer of the present invention
Ulcer, postoperative ulcer) external used medicine compound montmorillonite sucrose ointment, use montmorillonite for drug of the present invention it is effective at
Point, with selected pharmaceutic adjuvant, pass through the works such as moist heat sterilization, dissolving, low speed homogeneous, high speed homogenization, stirring, cooling, sterile filling
Medicament is made in skill.By external preparation for skin drug administration, to the skin ulcers of different times, (bedsore, scald ulcer, calf are burst
Ulcer, diabetic ulcer, postoperative ulcer after ulcer, with shape blebs) it is all shown with preferable clinical effect.Specifically
Effect experiment will be explained in experimental example.
With reference to experimental example, the present invention is described further, but not limited to this.
Experimental example 1, prescription screening and Optimal Experimental
Auxiliary material used in this ointment formulation is pharmaceutic adjuvant grade, for this preparation characteristic, formulates the prescription of preliminary screening.
Screened according to following prescription, respectively to character, uniformity, viscosity, heat-resisting (55 DEG C, 6h), it is cold-resistant (- 15 DEG C,
For 24 hours), lamination is investigated, and is therefrom selected optimal proportional quantity, is shown in Table 1：
1 compound montmorillonite sucrose ointment formulations of table screen (unit：g)
| Component | Prescription 1 | Prescription 2 | Prescription 3 | Prescription 4 | Prescription 5 | Prescription 6 |
| Montmorillonite | 50 | 50 | 50 | 50 | 50 | 50 |
| Sucrose | 410 | 410 | 410 | 410 | 410 | 410 |
| Macrogol 6000 | 1 | 2 | 3 | 4 | 5 | 7 |
| Glycerine | 1 | 2 | 3 | 4 | 5 | 7 |
| Sorbierite | 6 | 7 | 8 | 9 | 10 | 16 |
| Sodium alginate | 1 | 2 | 3 | 4 | 5 | 7 |
| Sterile water | 400 | 450 | 500 | 550 | 600 | 900 |
Preparation method：According to the method for embodiment 1；Prepare compound montmorillonite sucrose ointment.
Prescribed study the results are shown in Table 2：
2 prescription stability test result (unit of table：g)
Interpretation of result：The above prescription 1,2,3,4 made ointment have wild effect when examining, according to aforementioned stable
As a result, the ratio of prescription is convenient in display prescription 5,6.It based on the ratio of prescription 5,6, optimizes, further carries out
Development test.As a result see 3：
3 compound montmorillonite sucrose ointment formulations optimal screening (unit of table：g)
| Component | Prescription 7 | Prescription 8 | Prescription 9 | Prescription 10 | Prescription 11 | Prescription 12 |
| Montmorillonite | 50 | 50 | 50 | 50 | 50 | 50 |
| Sucrose | 410 | 410 | 410 | 410 | 410 | 410 |
| Macrogol 6000 | 5 | 5 | 6 | 6 | 7 | 7 |
| Glycerine | 5 | 5 | 6 | 6 | 7 | 7 |
| Sorbierite | 10 | 11 | 12 | 13 | 14 | 16 |
| Sodium alginate | 5 | 5 | 6 | 6 | 7 | 7 |
| Sterile water | 600 | 650 | 700 | 750 | 800 | 900 |
Preparation method：According to the method for embodiment 1；Prepare compound montmorillonite sucrose ointment；It is evaluated according to upper index, is as a result seen
4；
4 compound montmorillonite sucrose ointment formulations of table are evaluated and result：
| Prescription | 7 | 8 | 9 | 10 | 11 | 12 |
| Character | Milky | Milky | Milky | Milky | Milky | Milky |
| Uniformity | Uniformly | Uniformly | Uniformly | Uniformly | Uniformly | Uniformly |
| Viscosity | 70Pa.s | 68Pa.s | 68Pa.s | 67Pa.s | 67Pa.s | 66Pa.s |
| It is heat-resisting | Stablize | Stablize | Stablize | Stablize | Stablize | Stablize |
| It is cold-resistant | Stablize | Stablize | Stablize | Stablize | Stablize | Stablize |
| Lamination | Stablize | Stablize | Stablize | Stablize | Stablize | Stablize |
Conclusion:Ointment formulations 7~12；Respectively to character, uniformity, viscosity, heat-resisting (55 DEG C, 6h), it is cold-resistant (- 15 DEG C,
24h)；In this preparation, all indexs meet the requirements；From operation and economic consideration, in 6 final ointment formulations；Optimization
Prescription 7,8,9 is used as final optimization pass prescription.
Experimental example 2, montmorillonite sterilizing experiment
In the present invention, active constituent montmorillonite is the layer mineral being made of the superfine hydrous alumino silicates of particle, by
Basic igneous rock weathering in alkaline environment forms, and also has plenty of the product after the volcanic ash decomposition of sea-bottom deposit.According to China
Pharmacopeia version (annex IF) regulation in 2010 should reach sterile requirement when for the skin of large-area burns or severe trauma.Cause
This, this preparation supplementary material needs to sterilize, and sterile preparation is made in gnotobasis, for Clinical practice.Illiteracy currently on the market
De- stone sterilizing methods are all made of Co60Method of radiating, the related Co of health ministry60Irradiation sterilization dosage standard《Defend medicine hair 1,997 the
No. 38》In notice, Co60Irradiation sterilization maximum dose is 6KGY.Since montmorillonite is a kind of mineral drug, Co60Irradiation dose
6KGY can not penetrate montmorillonite, cause sterilization effect poor, and only be improved Co60Irradiation dose is 15KGY, considerably beyond country
6KGY maximum dose levels as defined in the Ministry of Public Health.Research montmorillonite sterilizing methods are to ensure that montmorillonite medicine meets the premise of quality standard
Under, ensure that montmorillonite medicine can be used safely, there is great strategic structural.
2.1 are added without the montmorillonite of sucrose in different moist heat sterilization temperature and times to montmorillonite moist heat sterilization effect
Compare, is shown in Table 5：
5 montmorillonite moist heat sterilization effect of table compares
By that can be analyzed in table 5：
(1) moist heat sterilization temperature is at 121~131 DEG C, the time under the conditions of 30~90min, montmorillonite x-ray diffraction pattern
Spectrum meets 2010 addendum of Chinese Pharmacopoeia regulation, shows with this condition not destroy montmorillonite chemical constitution, but sterile
It checks, it is against regulation.
(2) for moist heat sterilization temperature at 135 DEG C, the time meets middle traditional Chinese medicines in 30~90min, montmorillonite X-ray diffracting spectrum
2010 addendum of allusion quotation provides, shows with this condition not destroy montmorillonite chemical constitution, but sterility test, does not meet rule
It is fixed.
The montmorillonite of 2.2 addition sucrose is in different moist heat sterilization temperature and times to the ratio of montmorillonite moist heat sterilization effect
Compared with being shown in Table 6：
6 montmorillonite moist heat sterilization effect of table compares
By that can be analyzed in table 6：
(1) moist heat sterilization temperature is at 121~131 DEG C, the time under the conditions of 30~90min, montmorillonite x-ray diffraction pattern
Spectrum meets 2010 addendum of Chinese Pharmacopoeia regulation, shows with this condition not destroy montmorillonite chemical constitution, but sterile
It checks, it is against regulation.
(2) for moist heat sterilization temperature at 135 DEG C, the time meets Chinese Pharmacopoeia in 30min, montmorillonite X-ray diffracting spectrum
2010 addendums provide, show with this condition not destroy montmorillonite chemical constitution, sterility test is against regulation.
(3) for moist heat sterilization temperature at 135 DEG C, the time meets regulation, montmorillonite chemistry knot in 60~90min, sterility test
Structure does not destroy,
By upper experiment；Due to the hypertonicity of sucrose, change the osmotic pressure of liquid environment；In moist heat sterilization temperature at 135 DEG C,
Time meets regulation in 60min~90min, sterility test.
Experimental example 3, sucrose and auxiliary material sterilizing experiment
Comparison of the different moist heat sterilizations and time to sucrose and auxiliary material moist heat sterilization effect, is shown in Table 7：
7 sucrose of table and auxiliary material moist heat sterilization effect compare
By that can be analyzed in table 7：
1, for moist heat sterilization temperature at 121 DEG C, 131 DEG C, the time under the conditions of 30~90min, converts sugared content ＜ in sucrose
1.0% meets regulation, shows with this condition not destroy sucrochemistry structure, but sterility test, against regulation.
2, at 135 DEG C, the time converts sugared content ＜ 1.0% in 30min, sucrose and meets regulation, table moist heat sterilization temperature
Bright not destroyed with this condition to sucrochemistry structure, sterility test is against regulation.
3, at 135 DEG C, the time converts sugared content ＜ 1.0% in 60min, sucrose and meets regulation, table moist heat sterilization temperature
Bright not destroyed with this condition to sucrochemistry structure, sterility test meets regulation.
4, for moist heat sterilization temperature at 135 DEG C, the time in 90min, sterility test, meets regulation.But inverted sugar contains in sucrose
It is against regulation to measure ＜ 1.0%, shows with this condition to destroy sucrochemistry structure.
Experimental example 4, compound montmorillonite sucrose ointment promote the pharmacodynamic experiment of skin ulcer healing
1；Reagent and animal
Prepared by compound montmorillonite sucrose ointment embodiment 1, contractubex gel agent (Merz Pharma GmbH ＆ Co. KGAA) health male
Kunming mouse, 23~25g of weight are provided by Shandong University's Experimental Animal Center.
2；Method and result
The Healing of 2.1 pairs of skin trauma ulcer
The preparation of mouse back skin trauma model：Healthy male mice in kunming 20, with warp at left and right sides of back
The knife blade of disinfection shaves off the hair of size about 2.0 × 2.0cm respectively, and is made in the dilute hydrochloric acid that 0.01mol/L is subcutaneously injected
It is spare at trauma model.
Grouping, administration and observation index：30 mouse are randomly divided into 3 groups, every group 10, i.e. normal group of (hurtless measure pair
According to group, not medication), (2 groups of experiment, the positive are right for compound montmorillonite sucrose ointment group (experiment 1 group) and contractubex gel agent group
According to).Two test groups are administered at right side back respectively, and left side back is not administered (i.e. own control), and model is made next day afterwards and started
Medication:1 group is uniformly applied ointment 0.5g on ulcer surface, and 2 groups uniformly apply a thin layer on ulcer surface (about 0.5g gels, give daily
Medicine 2 times, continuous 10d, in 7d and the 10d days record ulcer areas.The 11d mornings put to death mouse, cut partial skin ulcer
Locate tissue, is fixed with formalin solution and carry out histological examination.Histological change is divided into 0 by the degree of inflammatory cell infiltration
(nothing), 1 (slight), 2 (moderates), the evaluation of 3 (severe) level Four.Will observation result carry out statistical procedures, (data withTable
Show, t is examined) it the results are shown in Table 8：
Healing of the table 8 to mouse trauma ulcer
Note：Compared with self-controlled group,*P ＜ 0.01；Compared with 2 groups of right side administrations of experiment,△P ＞ 0.05.
The Healing of 2.2 pairs of skin scald ulcer
The preparation of mouse back skin scald model：Healthy male mice in kunming 20 is shaved at back with sterilized
Then knife unhairing uses constant temperature and pressure electric pressing instrument, respectively with 60 DEG C, 8s, 2.0kpa are condition of causing injury, and are caused directly in mouse back
The skin minor scald wound (the scald number of degrees are about 1 degree) of diameter 2.0cm (account for about mouse body surface area 20%), it is spare.
Grouping, administration and observation index：30 mouse are randomly divided into 3 groups, every group 10, i.e., normal group (no scald pair
According to group, not medication), (2 groups of experiment, the positive are right for compound montmorillonite sucrose ointment group (experiment 1 group) and contractubex gel agent group
According to).Test group is administered at right side back respectively, and left side back is not administered (i.e. own control), and model immediately begins to use after making
Medicine：1 group uniformly applies ointment medicine 0.5g on ulcer surface, 2 groups of gels that a thin layer (about 0.5g) is uniformly applied on ulcer surface, daily
Administration 2 times, continuous 10d records ulcer area in 7d and 10d.The 11st day morning put to death mouse, cut partial skin ulcer
Locate tissue, histological examination is fixed and carried out with formalin solution, Histological change is divided by the degree of inflammatory cell infiltration
Standard is the same as 2.1.It the results are shown in Table 9.
Table 9 scalds mouse the Healing of ulcer
Note：Compared with self-controlled group,*P ＜ 0.01；Compared with 2 groups of right side administrations of experiment,△P ＞ 0.05.
2.3 local application's irritation tests
20 healthy male mice in kunming are randomly divided into two groups, every group 10, are gone with razor in mouse back skin
Except the mouse hair of size about 2.0 × 2.0cm, uniformly a thin layer is applied (about on a skin surface with compound montmorillonite sucrose ointment
0.5g), 2 times/d and 3 time/d is administered respectively, it is anti-to observe the irritation that different times for spraying generate mouse skin by continuous 14d
It answers.
The result shows that：During entire medication, it is anti-to be showed no the irritations such as redness, fash for skin at two groups of mouse administrations
It answers, when administration also has no that mouse has uncomfortable abnormal response.
The long-time stability experiment of experimental example 5, compound montmorillonite sucrose ointment
Long-time stability will be carried out under compound montmorillonite sucrose ointment storage requirement as defined in listing prepared by embodiment 1
Experiment investigates stability features of compound montmorillonite sucrose external use sterile ointment during transport, preservation, use, to make
To determine the foundation of the term of validity and storage requirement.Aluminum-plastic packaged compound montmorillonite sucrose ointment sample will be used, is positioned over 25
DEG C ± 2 DEG C, place 24 months in the constant temperature of RH60% ± 10%, constant humidity cabinet, sampled respectively at 0,3,6,9,12,18,24 month,
The every quality index of detection.It the results are shown in Table 10.
10 compound montmorillonite sucrose ointment long-time stability of table are tested
As a result：Through long-time stability investigation in 24 months, as a result show that indices are without significant change, table compared with 0 month
Bright compound montmorillonite sucrose ointment has good stability under the conditions of 25 DEG C ± 2 DEG C, RH60% ± 10%, in defined terms and conditions
Lower production, packaging, storage, transport will not have an adverse effect to the quality of this product, can ensure that clinical application is safe and effective.
Experimental example 6, clinical trial
1；Clinical data：General information this group 90, man 64；Female 26；The course of disease 30~350 days；Ulcer area is minimum
0.5cm × 0.5cm, maximum 20cm × 12cm；Wherein Buerger's disease occurs together ulcer 21, diabetes accompanying ulcer 9
Example, venous leg ulcers 36, wound infection ulcer 12, pressure ulcer 6, burn and scald ulcer 3, erythema induratum
With ulcer 2, panniculitis occurs together Ulcer: One Case of Report.90 patients are divided into 2 groups.Treatment group 58:Man 41, female 17；Age (48
~69) year；The course of disease 31~300 days；Sore face area (10.7 ± 9.6) cm2.Control group 32, man 23, female 9；Age (47
~60) year；The course of disease 30~350 days；Sore face area (10.5 ± 9.7) cm2.Two groups of general information statistical procedures, difference is without aobvious
Work property meaning (p ＞ 0.05), is comparable.
2；Therapy：
Treatment group's compound montmorillonite sucrose ointment is prepared by 1 method of embodiment, first with 75% cotton ball soaked in alcohol routine disinfection sore
All skin is inhaled sore face after being dipped in physiological saline cotton balls, then the medicine is coated on antiseptic gauze, and range is suitable with sore face, applies
Drug thickness degree is generally in 1~2mm, according to sore face secretion situation, daily or dressing every other day 1 time, with 4 weeks for 1 course for the treatment of.
Control group applies jingwanhong soft plaster (production of bis- factories of Tianjin Da Rentang) ointment outside, and usage is same as above.
3；Observation index and statistical method
Observation index three big routine, hepatic and renal function, electrocardiogram etc., with point-score to sore complexion pool degree, surface sepage amount,
Granulation and epithelial tissue growing state evaluate curative effect.
Statistical method total effects are analyzed using Ridit, are compared between multigroup mean and are examined with F.
4；Criterion of therapeutical effect and treatment results
Criterion of therapeutical effect reference《Chinese medical disease Standardization of diagnosis and curative effect》Middle evaluation curative effect.It cures：Ulcer healing；It improves：Ulcer
It reduces；It is not cured：Ulcer sore face has no diminution or has expansion.
5；2 groups of clinic total effects are relatively shown in Table 11.It is analyzed through Ridit, compared with the control group, difference is significant for treatment group
Meaning p ＜ 0.05.
11 two groups of clinic total effects of table compare
| Group | N | It cures | It improves | It is not cured | Healing time (day) |
| Treatment group | 58 | 38 | 10 | 10 | 21.5±12.7 |
| Control group | 32 | 8 | 18 | 6 | 40.6±18.5 |
6；The pretherapy and post-treatment indices score for the treatment of group, which is compared, is shown in Table 12.It is examined with F through comparing between multigroup mean, each time
Section compares, the significant meaning P ＜ of difference 0.05.
The pretherapy and post-treatment indices score of 12 treatment group of table is compared
Interpretation of result：In chronic ulcer of skin, local blood supply is the main reason for influence sore face is healed, and sore complexion
The change in pool is the external manifestation of local blood circulation, it is observed that 2 groups of sore complexion pool has clear improvement in the research, and is treated
Group is more notable.
Specific implementation mode
With reference to embodiment, the present invention is described further, but not limited to this.
Examples 1 to 3 supplementary material explanation：
| Material name | Manufacturing enterprise | Execution standard |
| Montmorillonite | Shandong Xianhe Pharmaceutical Co., Ltd. | 2010 addendum of Chinese Pharmacopoeia |
| Sorbierite | Hunan Er-kang Pharmaceutical Co., Ltd. | Chinese Pharmacopoeia 2010 editions two |
| Glycerine | Nantong Zhongbao Pharmaceutical Co., Ltd. | Chinese Pharmacopoeia 2010 editions two |
| Macrogol 6000 | Tianjin Tiancheng Pharmaceutical Co., Ltd. | Chinese Pharmacopoeia 2010 editions two |
| Sodium alginate | Qingdao bright moon seaweed group | Chinese Pharmacopoeia 2010 editions two |
| Sucrose | Hunan Er-kang Pharmaceutical Co., Ltd. | Chinese Pharmacopoeia 2010 editions two |
| Sterile water | Shandong Sibangde Pharmaceutical Co., Ltd. | Chinese Pharmacopoeia 2010 editions two |
Involved device and equipment are current ointment production common apparatus in embodiment, and market is commercially available.Illustrate such as
Under:The Zhengzhou stainless steel dissolving tank (model 100L) Yong Xin enamel chemical equipments Co., Ltd；The Wenzhou City cutter (model 50L) east
It is on sale to push up Machinery Manufacturing Co., Ltd..
Embodiment 1：The preparation of compound montmorillonite sucrose ointment
1, raw and auxiliary material inventory proportioning (w/w)：
2, it is prepared by the following method：
(1) montmorillonite, sucrose, Macrogol 6000, glycerine, sorbierite, sodium alginate, spare is weighed according to the ratio；
(2) montmorillonite, sucrose, Macrogol 6000, glycerine, sorbierite, sodium alginate, sterile water are put into dissolving tank
In, it opens and stirs and heat up, be continuously heating to 135 DEG C, sterilizing, the retention time is in 60min；Then after being cooled to 90 DEG C, heat preservation
It is spare；
(3) it by step (2) resulting material, aseptically, is pumped into shearing tank；Under the conditions of temperature 70 C, open
Cutter low speed 1800r/min is sheared 5 minutes, then high speed 3000r/min shearings 2 minutes；Cutter is closed, stirring is opened,
Rotating speed is 100r/min, continues stirring 4 minutes, is then stirred again for 60r/min in rotating speed, stops stirring when being cooled to 30 DEG C,
Compound montmorillonite sucrose ointment formulation product is made；
(4) it packs, examines, storage.
Compound montmorillonite sucrose ointment testing result：Differentiate：(1) montmorillonite, (2) sucrose are positive；Content (w/w)：
Montmorillonite 98.56%, sucrose 98.55%；The other indexs of compound montmorillonite sucrose ointment meet regulation.
Embodiment 2：The preparation of compound montmorillonite sucrose ointment
1, raw and auxiliary material inventory proportioning (w/w)：
2, it is prepared by the following method：
(1) montmorillonite, sucrose, Macrogol 6000, glycerine, sorbierite, sodium alginate, spare is weighed according to the ratio；
(2) montmorillonite, sucrose, Macrogol 6000, glycerine, sorbierite, sodium alginate, sterile water are put into dissolving tank
In, it opens and stirs and heat up, be continuously heating to 135 DEG C, sterilizing, the retention time is in 60min；Then after being cooled to 80 DEG C, heat preservation
It is spare；
(3) it by step (2) resulting material, aseptically, is pumped into shearing tank；Under the conditions of temperature 70 C, open
Cutter low speed 2000r/min is sheared 4 minutes, then high speed 3200r/min shearings 2 minutes；Cutter is closed, stirring is opened,
Rotating speed is 100r/min, continues stirring 2 minutes, is then stirred again for 80r/min in rotating speed, stops stirring when being cooled to 35 DEG C,
Compound montmorillonite sucrose ointment formulation product is made；
(4) it packs, examines, storage.
Compound montmorillonite sucrose ointment testing result：Differentiate：(1) montmorillonite, (2) sucrose are positive and are positive；Contain
It measures (w/w)：Montmorillonite 98.52%, sucrose 98.28%；The other indexs of compound montmorillonite sucrose ointment meet regulation.
Embodiment 3：The preparation of compound montmorillonite sucrose ointment
1, raw and auxiliary material inventory proportioning (w/w)：
2, it is prepared by the following method：
(1) montmorillonite, sucrose, Macrogol 6000, glycerine, sorbierite, sodium alginate, spare is weighed according to the ratio；
(2) montmorillonite, sucrose, Macrogol 6000, glycerine, sorbierite, sodium alginate, sterile water are put into dissolving tank
In, it opens and stirs and heat up, be continuously heating to 135 DEG C, sterilizing, the retention time is in 60min；Then after being cooled to 85 DEG C, heat preservation
It is spare；
(3) it by step (2) resulting material, aseptically, is pumped into shearing tank；Under the conditions of temperature 70 C, open
Cutter low speed 1900r/min is sheared 4 minutes, then high speed 3100r/min shearings 2 minutes；Cutter is closed, stirring is opened,
Rotating speed is 110r/min, continues stirring 4 minutes, is then stirred again for 60r/min in rotating speed, stops stirring when being cooled to 35 DEG C,
Compound montmorillonite sucrose ointment formulation product is made；
(4) it packs, examines, storage.
Compound montmorillonite sucrose ointment testing result：Differentiate：(1) montmorillonite, (2) sucrose are positive and are positive；Contain
It measures (w/w)：Montmorillonite 98.67%, sucrose 98.23%；The other indexs of compound montmorillonite sucrose ointment meet regulation.
Claims (3)
1. a kind of compound montmorillonite sucrose ointment for treating skin ulcer, which is characterized in that be made by mass parts of following raw material：
The granularity of montmorillonite is no more than 90 μm；
The compound montmorillonite sucrose ointment is containing 96.0%~110.0% that montmorillonite is labelled amount；Sucrose is labelled amount
95.0%~110.0%；
The compound montmorillonite sucrose ointment is prepared by the following method：
(1) montmorillonite, sucrose, Macrogol 6000, glycerine, sorbierite, sodium alginate, spare is weighed according to the ratio；
(2) it by montmorillonite, sucrose, Macrogol 6000, glycerine, sorbierite, sodium alginate, sterile water input dissolving tank, opens
It opens stirring and heats up, be continuously heating to 135 DEG C, sterilizing keeps 60min；Then after being cooled to 80~90 DEG C, heat preservation is spare；
(3) it by step (2) resulting material, aseptically, is pumped into shearing tank；Under the conditions of 65~70 DEG C of temperature, open
1800~2000r/min of cutter low speed is sheared 4~5 minutes, and then 3000~3200r/min is sheared 2~3 minutes at a high speed；It closes
It closes cutter, opens stirring, rotating speed is 100~110r/min, continues stirring 2~4 minutes, in rotating speed is again then 60~80r/
Min is stirred, and stops stirring when being cooled to 30~35 DEG C, compound montmorillonite sucrose ointment formulation product is made；
(4) it packs, examines, storage.
2. application of the compound montmorillonite sucrose ointment as described in claim 1 in the drug for preparing treatment skin ulcer.
3. application as claimed in claim 2, wherein the skin ulcer be decubitus ulcer, scald ulcer, calf ulcer,
Ulcer, diabetic ulcer, postoperative ulcer after with shape blebs.
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101415441A (en) * | 2006-04-10 | 2009-04-22 | 阿奎坦制药公司 | Healing composition |
| 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 |
| CN102178939A (en) * | 2011-05-06 | 2011-09-14 | 山东司邦得制药有限公司 | Muramidase hydrolase external sterile cream for treating skin ulcer and preparation method thereof |
| CN104586962A (en) * | 2015-01-21 | 2015-05-06 | 张金安 | Ointment for treating burn by promoting tissue regeneration and skin growth and preparation method of ointment |
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101415441A (en) * | 2006-04-10 | 2009-04-22 | 阿奎坦制药公司 | Healing composition |
| 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 |
| CN102178939A (en) * | 2011-05-06 | 2011-09-14 | 山东司邦得制药有限公司 | Muramidase hydrolase external sterile cream for treating skin ulcer and preparation method thereof |
| CN104586962A (en) * | 2015-01-21 | 2015-05-06 | 张金安 | Ointment for treating burn by promoting tissue regeneration and skin growth and preparation method of ointment |
Non-Patent Citations (2)
| Title |
|---|
| 白砂糖治疗皮肤溃疡;方选书;《四川中医》;19850531(第5期);第57页 * |
| 蒙脱石散治疗慢性皮肤溃疡;蒋卫健;《中外健康文摘》;20110228;第8卷(第7期);第206页 * |
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