CN104688717A - Drug combination containing lidocaine and prilocainum - Google Patents
Drug combination containing lidocaine and prilocainum Download PDFInfo
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- CN104688717A CN104688717A CN201510118390.7A CN201510118390A CN104688717A CN 104688717 A CN104688717 A CN 104688717A CN 201510118390 A CN201510118390 A CN 201510118390A CN 104688717 A CN104688717 A CN 104688717A
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- prilocaine
- lignocaine
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Abstract
The invention belongs to the technical field of medicine. The invention discloses a drug combination containing lidocaine and prilocainum. The drug combination containing lidocaine and prilocainum comprises lidocaine, prilocainum, Carbomer, a polyoxyethylene hydrogenated castor oil, and a pH regulator. It is tested by experiments that the drug combination containing lidocaine and prilocainum has a better safety and a better stability after being made into a cream.
Description
Technical field
The invention belongs to medical art, be specifically related to a kind of pharmaceutical composition containing lignocaine, prilocaine.
Background technology
Traditional compound lidocaine emulsifiable paste needs to add penetrating agent, if: azone and surfactant are as Tween 80 etc.Its objective is and destroy epiderm skin tissue to increase subcutaneous osmotic effect.But be prejudicial to skin like this, the object of safe medication can not be reached.Tween 80 has the effect of very strong ruptured cell film and causes zest, and medical circle confirms, Tween 80 can cause allergic reaction, and comprises shock, dyspnea, hypotension, angioedema, the anaphylactoid reaction symptoms such as rubella.These untoward reaction can be very serious in the clinical experiment of people, has dead report.Therefore, use Tween 80 to have qualification, it is a kind of adjuvant having potential insecurity, and improper use can make a big impact to the health of people.The toxicity produced therefrom will exceed the benefit that product itself brings.
There is following defect in traditional compound lidocaine emulsifiable paste production technology:
1, energy resource consumption is many: lignocaine and prilocaine need to mix in water-bath, are heated to the temperature of 80 degree, then also need pass into water quench in the interlayer of water-bath, and this process need is equipped with heating circulation system, cooling water recirculation system.Equipment investment is huge, and the production cycle is long, manual operation complex effects production efficiency.And power consumption is large, production cost is higher.
2, waste of raw materials is many: in traditional handicraft, polyoxyethylene hydrogenated Oleum Ricini feeding method is connected with stirred vessel by the storage capsule of polyoxyethylene hydrogenated Oleum Ricini, sucks imported through conveyance conduit by material through vacuum.Each convey materials all can make to leave over some residues in pipeline, causes the waste of raw material.
3, the production cycle is long: the production cycle of traditional handicraft needs 2 working days usually, and carbomer used and purified water are that soak time reaches 5-7 hour under ceaselessly stirring the same day, still need and carry out solubility property inspection.Production efficiency is low.
4, technology controlling and process is difficult, affect product stability: traditional compound lidocaine emulsifiable paste first in the aqueous solution of carbomer, adds sodium hydroxide to make it dissolve each other, and then add lignocaine in the eutectic mixture of prilocaine, last repeated hydrogenation sodium hydroxide solution carries out adjust ph, but when the aqueous solution that sodium hydroxide solution adds carbomer mixes, whether suitable operation will directly affect mixed solution viscosity values to add the factors such as speed, mixing speed, time controling, personnel.Viscosity or high or low emulsifying effectiveness and the permeance property that all will affect product.
Summary of the invention
Applicant finds under study for action, lignocaine, although prilocaine emulsifiable paste is extensive in clinical practice, but it has certain zest, certain misery is brought to patient, and this zest is likely emulsifiable paste adjuvant or related substance increases and cause, therefore, applicant is by repeatedly creative experimental study, obtain a kind of new lignocaine, prilocaine emulsifiable paste, this emulsifiable paste is by lignocaine, prilocaine, carbomer, butanolamine and monoethanolamine are that raw material prepares, pass through zest, stability screening test, wherein a certain proportion of butanolamine and monoethanolamine are for lignocaine, the related substance variable effect of prilocaine ointment is less, there is better safety and stability.
The present invention is achieved through the following technical solutions.
A pharmaceutical composition containing lignocaine, prilocaine, comprising: lignocaine, prilocaine, carbomer, polyoxyethylene hydrogenated Oleum Ricini, pH adjusting agent.
Described pH adjusting agent is one or more in sodium hydroxide, butanolamine, monoethanolamine.
Described pharmaceutical composition comprises: lignocaine 40-60 weight portion, prilocaine 40-60 weight portion, carbomer 16-20 weight portion, sodium hydroxide 7-9 weight portion, polyoxyethylene hydrogenated Oleum Ricini 30-36 weight portion.
Described pharmaceutical composition comprises: lignocaine, prilocaine, carbomer, polyoxyethylene hydrogenated Oleum Ricini, butanolamine and monoethanolamine.
Described pharmaceutical composition comprises: lignocaine 40-60 weight portion, prilocaine 40-60 weight portion, carbomer 16-20 weight portion, polyoxyethylene hydrogenated Oleum Ricini 30-36 weight portion, butanolamine and monoethanolamine 6-8 weight portion.
Wherein the weight ratio of butanolamine and monoethanolamine is 1:0.60-0.80.
Described pharmaceutical composition is prepared into pharmaceutical preparation.
Described pharmaceutical preparation comprises ointment.
The preparation method of described ointment includes but not limited to:
Step 1: in advance carbomer is added purified water and be dipped to that carbomer is disperseed completely is for subsequent use.
Step 2: lignocaine and prilocaine are dropped in stirred vessel with 1 ︰ 1 weight ratio, is uniformly mixed the eutectic mixture into eutectic at normal temperatures;
Step 3: polyoxyethylene hydrogenated Oleum Ricini is directly added in above-mentioned stirred vessel, stir with the eutectic mixture of eutectic, become water in oil oil mixture;
Step 4: mixed with the oil mixture formed in step 3 by the carbomer of step 1 gained, stirs into oil-in-water mixture;
Step 5: add pH adjusting agent in above-mentioned stirred vessel;
Step 6: add purified water in stirred vessel, is stirred into emulsifiable paste;
Step 7: after homogenizing, fill.
Described pharmaceutical composition is preparing the application in anaesthetic.
Goal of the invention of the present invention is that a kind of zest is little, related substance changes little ointment in order to obtain, and this ointment has better stability and safety, significant for clinical application.
Following experimental study is on test of many times basis, the concluding demonstration testing that the technical scheme for the present invention's protection is carried out.
One, zest screening test
Test 1 group: lignocaine 45g, prilocaine 45g, carbomer940 18g, sodium hydroxide 8.5g, polyoxyethylene-(54)-castor oil hydrogenated 34.2g.
Preparation method:
Step 1: in advance carbomer is added purified water and be dipped to that carbomer is disperseed completely is for subsequent use.
Step 2: lignocaine and prilocaine are dropped in stirred vessel with 1 ︰ 1 weight ratio, is uniformly mixed the eutectic mixture into eutectic at normal temperatures;
Step 3: polyoxyethylene hydrogenated Oleum Ricini is directly added in above-mentioned stirred vessel, stir with the eutectic mixture of eutectic, become water in oil oil mixture;
Step 4: mixed with the oil mixture formed in step 3 by the carbomer of step 1 gained, stirs into oil-in-water mixture;
Step 5: add 8% sodium hydrate aqueous solution in above-mentioned stirred vessel;
Step 6: add purified water in stirred vessel, is stirred into emulsifiable paste;
Step 7: after homogenizing, fill, obtains ointment 1000.
Test 2 groups: lignocaine 45g, prilocaine 45g, carbomer940 18g, diethanolamine 8.5g, polyoxyethylene-(54)-castor oil hydrogenated 34.2g.
Preparation method:
Step 1: in advance carbomer is added purified water and be dipped to that carbomer is disperseed completely is for subsequent use.
Step 2: lignocaine and prilocaine are dropped in stirred vessel with 1 ︰ 1 weight ratio, is uniformly mixed the eutectic mixture into eutectic at normal temperatures;
Step 3: polyoxyethylene hydrogenated Oleum Ricini is directly added in above-mentioned stirred vessel, stir with the eutectic mixture of eutectic, become water in oil oil mixture;
Step 4: mixed with the oil mixture formed in step 3 by the carbomer of step 1 gained, stirs into oil-in-water mixture;
Step 5: add diethanolamine in above-mentioned stirred vessel;
Step 6: add purified water in stirred vessel, is stirred into emulsifiable paste;
Step 7: after homogenizing, fill, obtains ointment 1000.
Test 3 groups: lignocaine 45g, prilocaine 45g, carbomer940 18g, diisopropylamine 8.5g, polyoxyethylene-(54)-castor oil hydrogenated 34.2g.
Preparation method:
Step 1: in advance carbomer is added purified water and be dipped to that carbomer is disperseed completely is for subsequent use.
Step 2: lignocaine and prilocaine are dropped in stirred vessel with 1 ︰ 1 weight ratio, is uniformly mixed the eutectic mixture into eutectic at normal temperatures;
Step 3: polyoxyethylene hydrogenated Oleum Ricini is directly added in above-mentioned stirred vessel, stir with the eutectic mixture of eutectic, become water in oil oil mixture;
Step 4: mixed with the oil mixture formed in step 3 by the carbomer of step 1 gained, stirs into oil-in-water mixture;
Step 5: add diisopropylamine in above-mentioned stirred vessel;
Step 6: add purified water in stirred vessel, is stirred into emulsifiable paste;
Step 7: after homogenizing, fill, obtains ointment 1000.
Test 4 groups: lignocaine 45g, prilocaine 45g, carbomer940 18g, triethanolamine 7.5g, polyoxyethylene-(54)-castor oil hydrogenated 34.2g.
Preparation method:
Step 1: in advance carbomer is added purified water and be dipped to that carbomer is disperseed completely is for subsequent use.
Step 2: lignocaine and prilocaine are dropped in stirred vessel with 1 ︰ 1 weight ratio, is uniformly mixed the eutectic mixture into eutectic at normal temperatures;
Step 3: polyoxyethylene hydrogenated Oleum Ricini is directly added in above-mentioned stirred vessel, stir with the eutectic mixture of eutectic, become water in oil oil mixture;
Step 4: mixed with the oil mixture formed in step 3 by the carbomer of step 1 gained, stirs into oil-in-water mixture;
Step 5: add triethanolamine in above-mentioned stirred vessel;
Step 6: add purified water in stirred vessel, is stirred into emulsifiable paste;
Step 7: after homogenizing, fill, obtains ointment 1000.
Test 5 groups: lignocaine 45g, prilocaine 45g, carbomer940 18g, triethanolamine 2.5g, butanolamine 5g, polyoxyethylene-(54)-castor oil hydrogenated 34.2g.
Preparation method:
Step 1: in advance carbomer is added purified water and be dipped to that carbomer is disperseed completely is for subsequent use;
Step 2: lignocaine and prilocaine are dropped in stirred vessel with 1 ︰ 1 weight ratio, is uniformly mixed the eutectic mixture into eutectic at normal temperatures;
Step 3: polyoxyethylene hydrogenated Oleum Ricini is directly added in above-mentioned stirred vessel, stir with the eutectic mixture of eutectic, become water in oil oil mixture;
Step 4: mixed with the oil mixture formed in step 3 by the carbomer of step 1 gained, stirs into oil-in-water mixture;
Step 5: add triethanolamine and butanolamine in above-mentioned stirred vessel;
Step 6: add purified water in stirred vessel, is stirred into emulsifiable paste;
Step 7: fill after homogenizing, obtains ointment 1000.
Test 6 groups: lignocaine 45g, prilocaine 45g, carbomer940 18g, monoethanolamine 2.50g, butanolamine 5g, polyoxyethylene-(54)-castor oil hydrogenated 34.2g.
Preparation method:
Step 1: in advance carbomer is added purified water and be dipped to that carbomer is disperseed completely is for subsequent use.
Step 2: lignocaine and prilocaine are dropped in stirred vessel with 1 ︰ 1 weight ratio, is uniformly mixed the eutectic mixture into eutectic at normal temperatures;
Step 3: polyoxyethylene hydrogenated Oleum Ricini is directly added in above-mentioned stirred vessel, stir with the eutectic mixture of eutectic, become water in oil oil mixture;
Step 4: mixed with the oil mixture formed in step 3 by the carbomer of step 1 gained, stirs into oil-in-water mixture;
Step 5: add monoethanolamine and butanolamine in above-mentioned stirred vessel;
Step 6: add purified water in stirred vessel, is stirred into emulsifiable paste;
Step 7: after homogenizing, fill, obtains ointment 1000.
Test method: get rabbit 40, be divided into 8 groups at random, 24h before test, shaves off its spinal column diamond wool, can not lesional epidermis, each 3cm × 3cm in unhairing scope left and right.After 24h, the intact animal of skin health is selected to test.Be respectively blank group, mechanical stimulus group, test 1 group-test 6 groups.Get given the test agent 0.5g to be directly coated on skin, cover with 4 layers of gauze (2.5cm × 2.5cm) and one deck cellophane, then fixed with nonirritant adhesive plaster and binder.Adopt blocking test, the application time is 4h.After off-test, remove residual given the test agent with warm water.Observe 14 days.1h, 24h, 48h, 72h after removing given the test agent observe the dermoreaction of recipient site respectively, dermoreaction scoring is carried out by table 1, overall merit is carried out with the meansigma methods of animal subject integration, respectively observe time point top average according to 24h, 48h and 72h, judge skin irritation intensity by table 2.Experimental result is in table 3.
Table 1 skin wound repair is marked
Table 2 skin irritation strength grading standard
| Integral mean value * | Strength grading |
| 0~ | Nonirritant |
| 0.5~ | Slight zest |
| 2.0~ | Moderate zest |
| 6.0~ | Strong and stimulating |
* the top average of observing time point is referred to.
Table 3 rabbit skin irritation test result
| Group | Number of cases (only) | Congested | Edema | Total score |
| Blank | 8 | 0.3 | 0.1 | 0.4 |
| Mechanical stimulus | 8 | 4.1 | 2.2 | 6.3 |
| Test 1 group | 8 | 3.1 | 2.4 | 5.5 |
| Test 2 groups | 8 | 4.6 | 3.5 | 8.1 |
| Test 3 groups | 8 | 3.8 | 3.5 | 7.3 |
| Test 4 groups | 8 | 3.7 | 2.6 | 6.3 |
| Test 5 groups | 8 | 2.6 | 1.1 | 3.7 |
| Test 6 groups | 8 | 1.4 | 0.1 | 1.5 |
Conclusion (of pressure testing): above-mentioned test shows, test 2 groups and be greater than 6 points to the test zest total scores of 4 groups, therefore applicant gives up this test group, and tests 1 group, tests 5 groups, tests 6 groups of zests and be less than 6 points, and applicant retains this 3 groups of groups.
Two, stability test
Test method: the ointment of 6 groups got and test 1 group, test 5 groups, test is placed 10 days at temperature 60 C temperature, in the 5th day and sampling in the 10th day, detection level and related substance, result of the test was in table 2.
It is appropriate that [related substance detection] gets emulsifiable paste, add mobile phase (with assay mobile phase) dissolve and make every 1ml about containing the solution of lignocaine 100 μ g, prilocaine 100 μ g, as need testing solution, it is appropriate that precision measures need testing solution, add mobile phase and be diluted to the solution of every 1ml containing 2 μ g, solution in contrast.According to the chromatographic condition under assay item, get contrast solution 10 μ l injection liquid chromatography, record chromatogram is to 2 times of main constituent peak retention time.As aobvious impurity peaks in the chromatogram of need testing solution, each impurity peak area sum, must not be greater than 0.25 times (being less than 0.5%) of contrast solution chromatogram main constituent area.
[assay] measures according to high performance liquid chromatography (Chinese Pharmacopoeia version in 2010 two annex VD)
Chromatographic condition and system suitability octadecylsilane chemically bonded silica are filler, with acetonitrile: water: sodium dihydrogen phosphate: sodium lauryl sulphate (300ml:200ml:1.7g:0.85g) is mobile phase, flow velocity 1ml/min, determined wavelength 345nm.Number of theoretical plate is not less than 1500 by lignocaine.
Get ointment appropriate (being about equivalent to lignocaine 10mg), put in 100ml measuring bottle, add mobile phase and dissolve, be diluted to scale, shake up, as need testing solution, get 10 μ l injection liquid chromatographies, record chromatogram; Separately get lignocaine reference substance appropriate, add mobile phase and dissolve and dilute the reference substance solution made every 1ml and contain 100 μ g, be measured in the same method, by external standard method with calculated by peak area, obtain final product.
The different preparation stability result of the test of table 2
Conclusion (of pressure testing): aforementioned stable test shows, tests 1 group, tests 5 groups after hot test, its related substance has increased very large, and does not meet prescription, therefore should give up.
Three, ratio screening test
Test 1 group: lignocaine 45g, prilocaine 45g, carbomer940 18g, polyoxyethylene-(54)-castor oil hydrogenated 34.2g, monoethanolamine 2.5g, butanolamine 5.0g.
Test 2 groups: lignocaine 45g, prilocaine 45g, carbomer940 18g, polyoxyethylene-(54)-castor oil hydrogenated 34.2g, monoethanolamine 3.3g, butanolamine 4.2g.
Test 3 groups: lignocaine 45g, prilocaine 45g, carbomer940 18g, polyoxyethylene-(54)-castor oil hydrogenated 34.2g, monoethanolamine 3.4g, butanolamine 4.1g.
Test 4 groups: lignocaine 45g, prilocaine 45g, carbomer940 18g, polyoxyethylene-(54)-castor oil hydrogenated 34.2g, monoethanolamine 3.0g, butanolamine 4.5g.
Test 5 groups: lignocaine 45g, prilocaine 45g, carbomer940 18g, polyoxyethylene-(54)-castor oil hydrogenated 34.2g, monoethanolamine 3.1g, butanolamine 4.4g.
Preparation method:
Step 1: in advance carbomer is added purified water and be dipped to that carbomer is disperseed completely is for subsequent use.
Step 2: lignocaine and prilocaine are dropped in stirred vessel with 1 ︰ 1 weight ratio, is uniformly mixed the eutectic mixture into eutectic at normal temperatures;
Step 3: polyoxyethylene hydrogenated Oleum Ricini is directly added in above-mentioned stirred vessel, stir with the eutectic mixture of eutectic, become water in oil oil mixture;
Step 4: mixed with the oil mixture formed in step 3 by the carbomer of step 1 gained, stirs into oil-in-water mixture;
Step 5: add monoethanolamine in above-mentioned stirred vessel, butanolamine;
Step 6: add purified water in stirred vessel, is stirred into emulsifiable paste;
Step 7: after homogenizing, fill, obtains ointment 1000.
Irritation test: with test one, result of the test is in table 4.
Stability test: with test two, result of the test is in table 5.
Table 4 rabbit skin irritation test result
| Group | Number of cases (only) | Congested | Edema | Total score |
| Blank | 8 | 0.2 | 0.1 | 0.3 |
| Mechanical stimulus | 8 | 3.9 | 2.3 | 6.2 |
| Test 1 group | 8 | 1.5 | 0.2 | 1.7 |
| Test 2 groups | 8 | 1.4 | 0.4 | 1.8 |
| Test 3 groups | 8 | 1.4 | 0.5 | 1.9 |
| Test 4 groups | 8 | 1.5 | 0.4 | 1.9 |
| Test 5 groups | 8 | 1.6 | 0.2 | 1.8 |
Conclusion (of pressure testing): test data shows, the ratio of monoethanolamine and butanolamine, little for zest impact.
The different preparation stability result of the test of table 5
Test brief summary: above-mentioned data show, the weight ratio of butanolamine and monoethanolamine is less than 1:0.60, or when being greater than 1:0.80, after 10 days high temperature, its related substance is greater than 0.50%, do not meet the requirement of quality standard, therefore applicant retains the weight ratio of butanolamine and monoethanolamine is 1:0.60-0.80.
preparation embodiment
Embodiment 1
Lignocaine 45g, prilocaine 45g, carbomer940 18g, polyoxyethylene-(54)-castor oil hydrogenated 34.2g, monoethanolamine 3.2g, butanolamine 4.3g.
Preparation method:
Step 1: in advance carbomer is added purified water and be dipped to that carbomer is disperseed completely is for subsequent use.
Step 2: lignocaine and prilocaine are dropped in stirred vessel with 1 ︰ 1 weight ratio, is uniformly mixed the eutectic mixture into eutectic at normal temperatures;
Step 3: polyoxyethylene hydrogenated Oleum Ricini is directly added in above-mentioned stirred vessel, stir with the eutectic mixture of eutectic, become water in oil oil mixture;
Step 4: mixed with the oil mixture formed in step 3 by the carbomer of step 1 gained, stirs into oil-in-water mixture;
Step 5: add monoethanolamine in above-mentioned stirred vessel, butanolamine;
Step 6: add purified water in stirred vessel, is stirred into emulsifiable paste;
Step 7: after homogenizing, fill, obtains ointment 1000.
Embodiment 2
Lignocaine 45g, prilocaine 45g, carbomer940 18g, polyoxyethylene-(54)-castor oil hydrogenated 34.2g, monoethanolamine 3.2g, butanolamine 4.3g.
Preparation method:
Step 1: in advance carbomer is added purified water and be dipped to that carbomer is disperseed completely is for subsequent use.
Step 2: lignocaine and prilocaine are dropped in stirred vessel with 1 ︰ 1 weight ratio, is uniformly mixed the eutectic mixture into eutectic at normal temperatures;
Step 3: polyoxyethylene hydrogenated Oleum Ricini is directly added in above-mentioned stirred vessel, stir with the eutectic mixture of eutectic, become water in oil oil mixture;
Step 4: mixed with the oil mixture formed in step 3 by the carbomer of step 1 gained, stirs into oil-in-water mixture;
Step 5: add monoethanolamine in above-mentioned stirred vessel, butanolamine;
Step 6: add purified water in stirred vessel, is stirred into emulsifiable paste;
Step 7: after homogenizing, fill, obtains ointment 1000.
Embodiment 3
Lignocaine 45g, prilocaine 45g, carbomer940 19.6g, polyoxyethylene-(54)-castor oil hydrogenated 35.8g, monoethanolamine 2.7g, butanolamine 3.8g.
Preparation method:
Step 1: in advance carbomer is added purified water and be dipped to that carbomer is disperseed completely is for subsequent use.
Step 2: lignocaine and prilocaine are dropped in stirred vessel with 1 ︰ 1 weight ratio, is uniformly mixed the eutectic mixture into eutectic at normal temperatures;
Step 3: polyoxyethylene hydrogenated Oleum Ricini is directly added in above-mentioned stirred vessel, stir with the eutectic mixture of eutectic, become water in oil oil mixture;
Step 4: mixed with the oil mixture formed in step 3 by the carbomer of step 1 gained, stirs into oil-in-water mixture;
Step 5: add monoethanolamine in above-mentioned stirred vessel, butanolamine;
Step 6: add purified water in stirred vessel, is stirred into emulsifiable paste;
Step 7: after homogenizing, fill, obtains ointment 1000.
Embodiment 4
Lignocaine 45g, prilocaine 45g, carbomer940 16.5g, polyoxyethylene-(54)-castor oil hydrogenated 31 g, monoethanolamine 3.1g, butanolamine 4.9g.
Preparation method:
Step 1: in advance carbomer is added purified water and be dipped to that carbomer is disperseed completely is for subsequent use.
Step 2: lignocaine and prilocaine are dropped in stirred vessel with 1 ︰ 1 weight ratio, is uniformly mixed the eutectic mixture into eutectic at normal temperatures;
Step 3: polyoxyethylene hydrogenated Oleum Ricini is directly added in above-mentioned stirred vessel, stir with the eutectic mixture of eutectic, become water in oil oil mixture;
Step 4: mixed with the oil mixture formed in step 3 by the carbomer of step 1 gained, stirs into oil-in-water mixture;
Step 5: add monoethanolamine in above-mentioned stirred vessel, butanolamine;
Step 6: add purified water in stirred vessel, is stirred into emulsifiable paste;
Step 7: after homogenizing, fill, obtains ointment 1000.
Embodiment 5
Lignocaine 45g, prilocaine 45g, carbomer940 18g, polyoxyethylene-(54)-castor oil hydrogenated 35.8g, monoethanolamine 2.7g, butanolamine 4.6g.
Preparation method:
Step 1: in advance carbomer is added purified water and be dipped to that carbomer is disperseed completely is for subsequent use.
Step 2: lignocaine and prilocaine are dropped in stirred vessel with 1 ︰ 1 weight ratio, is uniformly mixed the eutectic mixture into eutectic at normal temperatures;
Step 3: polyoxyethylene hydrogenated Oleum Ricini is directly added in above-mentioned stirred vessel, stir with the eutectic mixture of eutectic, become water in oil oil mixture;
Step 4: mixed with the oil mixture formed in step 3 by the carbomer of step 1 gained, stirs into oil-in-water mixture;
Step 5: add monoethanolamine in above-mentioned stirred vessel, butanolamine;
Step 6: add purified water in stirred vessel, is stirred into emulsifiable paste;
Step 7: after homogenizing, fill, obtains ointment 1000.
Embodiment 6
Lignocaine 45g, prilocaine 45g, carbomer940 18g, polyoxyethylene-(54)-castor oil hydrogenated 34.2g, monoethanolamine 3.0g, butanolamine 4.5g.
Preparation method:
Step 1: in advance carbomer is added purified water and be dipped to that carbomer is disperseed completely is for subsequent use.
Step 2: lignocaine and prilocaine are dropped in stirred vessel with 1 ︰ 1 weight ratio, is uniformly mixed the eutectic mixture into eutectic at normal temperatures;
Step 3: polyoxyethylene hydrogenated Oleum Ricini is directly added in above-mentioned stirred vessel, stir with the eutectic mixture of eutectic, become water in oil oil mixture;
Step 4: mixed with the oil mixture formed in step 3 by the carbomer of step 1 gained, stirs into oil-in-water mixture;
Step 5: add monoethanolamine in above-mentioned stirred vessel, butanolamine;
Step 6: add purified water in stirred vessel, is stirred into emulsifiable paste;
Step 7: after homogenizing, fill, obtains ointment 1000.
Embodiment 7
Lignocaine 45g, prilocaine 45g, carbomer940 17.5g, polyoxyethylene-(54)-castor oil hydrogenated 33g, monoethanolamine 3.7g, butanolamine 4.8g.
Preparation method:
Step 1: in advance carbomer is added purified water and be dipped to that carbomer is disperseed completely is for subsequent use.
Step 2: lignocaine and prilocaine are dropped in stirred vessel with 1 ︰ 1 weight ratio, is uniformly mixed the eutectic mixture into eutectic at normal temperatures;
Step 3: polyoxyethylene hydrogenated Oleum Ricini is directly added in above-mentioned stirred vessel, stir with the eutectic mixture of eutectic, become water in oil oil mixture;
Step 4: mixed with the oil mixture formed in step 3 by the carbomer of step 1 gained, stirs into oil-in-water mixture;
Step 5: add monoethanolamine in above-mentioned stirred vessel, butanolamine;
Step 6: add purified water in stirred vessel, is stirred into emulsifiable paste;
Step 7: after homogenizing, fill, obtains ointment 1000.
Embodiment 8
Lignocaine 45g, prilocaine 45g, carbomer940 16g, polyoxyethylene-(54)-castor oil hydrogenated 30g, monoethanolamine 3.0g, butanolamine 4.5g.
Preparation method:
Step 1: in advance carbomer is added purified water and be dipped to that carbomer is disperseed completely is for subsequent use.
Step 2: lignocaine and prilocaine are dropped in stirred vessel with 1 ︰ 1 weight ratio, is uniformly mixed the eutectic mixture into eutectic at normal temperatures;
Step 3: polyoxyethylene hydrogenated Oleum Ricini is directly added in above-mentioned stirred vessel, stir with the eutectic mixture of eutectic, become water in oil oil mixture;
Step 4: mixed with the oil mixture formed in step 3 by the carbomer of step 1 gained, stirs into oil-in-water mixture;
Step 5: add monoethanolamine in above-mentioned stirred vessel, butanolamine;
Step 6: add purified water in stirred vessel, is stirred into emulsifiable paste;
Step 7: after homogenizing, fill, obtains ointment 1000.
Embodiment 9
Lignocaine 45g, prilocaine 45g, carbomer940 16g, polyoxyethylene-(54)-castor oil hydrogenated 33.7g, monoethanolamine 2.6g, butanolamine 3.4g.
Preparation method:
Step 1: in advance carbomer is added purified water and be dipped to that carbomer is disperseed completely is for subsequent use.
Step 2: lignocaine and prilocaine are dropped in stirred vessel with 1 ︰ 1 weight ratio, is uniformly mixed the eutectic mixture into eutectic at normal temperatures;
Step 3: polyoxyethylene hydrogenated Oleum Ricini is directly added in above-mentioned stirred vessel, stir with the eutectic mixture of eutectic, become water in oil oil mixture;
Step 4: mixed with the oil mixture formed in step 3 by the carbomer of step 1 gained, stirs into oil-in-water mixture;
Step 5: add monoethanolamine in above-mentioned stirred vessel, butanolamine;
Step 6: add purified water in stirred vessel, is stirred into emulsifiable paste;
Step 7: after homogenizing, fill, obtains ointment 1000.
Embodiment 10
Lignocaine 45g, prilocaine 45g, carbomer940 18.5g, polyoxyethylene-(54)-castor oil hydrogenated 35.3g, monoethanolamine 2.25g, butanolamine 3.75g.
Preparation method:
Step 1: in advance carbomer is added purified water and be dipped to that carbomer is disperseed completely is for subsequent use.
Step 2: lignocaine and prilocaine are dropped in stirred vessel with 1 ︰ 1 weight ratio, is uniformly mixed the eutectic mixture into eutectic at normal temperatures;
Step 3: polyoxyethylene hydrogenated Oleum Ricini is directly added in above-mentioned stirred vessel, stir with the eutectic mixture of eutectic, become water in oil oil mixture;
Step 4: mixed with the oil mixture formed in step 3 by the carbomer of step 1 gained, stirs into oil-in-water mixture;
Step 5: add monoethanolamine in above-mentioned stirred vessel, butanolamine;
Step 6: add purified water in stirred vessel, is stirred into emulsifiable paste;
Step 7: after homogenizing, fill, obtains ointment 1000.
Embodiment 11
Lignocaine 45g, prilocaine 45g, carbomer940 19g, polyoxyethylene-(54)-castor oil hydrogenated 35g, monoethanolamine 3g, butanolamine 5g.
Preparation method: step 1: in advance carbomer is added purified water and be dipped to that carbomer is disperseed completely is for subsequent use.
Step 2: lignocaine and prilocaine are dropped in stirred vessel with 1 ︰ 1 weight ratio, is uniformly mixed the eutectic mixture into eutectic at normal temperatures;
Step 3: polyoxyethylene hydrogenated Oleum Ricini is directly added in above-mentioned stirred vessel, stir with the eutectic mixture of eutectic, become water in oil oil mixture;
Step 4: mixed with the oil mixture formed in step 3 by the carbomer of step 1 gained, stirs into oil-in-water mixture;
Step 5: add monoethanolamine in above-mentioned stirred vessel, butanolamine;
Step 6: add purified water in stirred vessel, is stirred into emulsifiable paste;
Step 7: after homogenizing, fill, obtains ointment 1000.
Embodiment 12
Lignocaine 45g, prilocaine 45g, carbomer940 16g, polyoxyethylene-(54)-castor oil hydrogenated 36g, monoethanolamine 3.5g, butanolamine 4.5g.
Preparation method:
Step 1: in advance carbomer is added purified water and be dipped to that carbomer is disperseed completely is for subsequent use.
Step 2: lignocaine and prilocaine are dropped in stirred vessel with 1 ︰ 1 weight ratio, is uniformly mixed the eutectic mixture into eutectic at normal temperatures;
Step 3: polyoxyethylene hydrogenated Oleum Ricini is directly added in above-mentioned stirred vessel, stir with the eutectic mixture of eutectic, become water in oil oil mixture;
Step 4: mixed with the oil mixture formed in step 3 by the carbomer of step 1 gained, stirs into oil-in-water mixture;
Step 5: add monoethanolamine in above-mentioned stirred vessel, butanolamine;
Step 6: add purified water in stirred vessel, is stirred into emulsifiable paste;
Step 7: after homogenizing, fill, obtains ointment 1000.
An irritation test method of being tested to specifications by above-described embodiment is tested, and the ointment zest total score obtaining above-described embodiment is all less than 2.0; Test two stability tests to specifications, after obtaining the emulsifiable paste hot test in 10 days of above-described embodiment, its related substance is all less than 0.50%.
Preparation embodiment includes but not limited to above-mentioned.
Claims (10)
1. the pharmaceutical composition containing lignocaine, prilocaine, is characterized in that this pharmaceutical composition comprises: lignocaine, prilocaine, carbomer, polyoxyethylene hydrogenated Oleum Ricini, pH adjusting agent.
2. a kind of pharmaceutical composition containing lignocaine, prilocaine according to claim 1, wherein pH adjusting agent is one or more in sodium hydroxide, butanolamine, monoethanolamine.
3. a kind of pharmaceutical composition containing lignocaine, prilocaine according to claim 1 and 2, it is characterized in that described pharmaceutical composition comprises: lignocaine 40-60 weight portion, prilocaine 40-60 weight portion, carbomer 16-20 weight portion, sodium hydroxide 7-9 weight portion, polyoxyethylene hydrogenated Oleum Ricini 30-36 weight portion.
4. the pharmaceutical composition containing lignocaine, prilocaine, is characterized in that this pharmaceutical composition comprises: lignocaine, prilocaine, carbomer, polyoxyethylene hydrogenated Oleum Ricini, butanolamine and monoethanolamine.
5. a kind of pharmaceutical composition containing lignocaine, prilocaine according to claim 4, is characterized in that described pharmaceutical composition comprises: lignocaine 40-60 weight portion, prilocaine 40-60 weight portion, carbomer 16-20 weight portion, polyoxyethylene hydrogenated Oleum Ricini 30-36 weight portion, butanolamine and monoethanolamine 6-8 weight portion.
6. a kind of pharmaceutical composition containing lignocaine, prilocaine according to claim 5, wherein the weight ratio of butanolamine and monoethanolamine is 1:0.60-0.80.
7. a kind of pharmaceutical composition containing lignocaine, prilocaine according to claim 3,4 or 5, is characterized in that pharmaceutical composition is prepared into pharmaceutical preparation.
8. a kind of pharmaceutical composition containing lignocaine, prilocaine according to claim 7, its pharmaceutical formulations comprises ointment.
9. a kind of pharmaceutical composition containing lignocaine, prilocaine according to claim 8, wherein the preparation method of ointment is:
Step 1: in advance carbomer is added purified water and be dipped to that carbomer is disperseed completely is for subsequent use;
Step 2: lignocaine and prilocaine are dropped in stirred vessel with 1 ︰ 1 weight ratio, is uniformly mixed the eutectic mixture into eutectic at normal temperatures;
Step 3: polyoxyethylene hydrogenated Oleum Ricini is directly added in above-mentioned stirred vessel, stir with the eutectic mixture of eutectic, become water in oil oil mixture;
Step 4: mixed with the oil mixture formed in step 3 by the carbomer of step 1 gained, stirs into oil-in-water mixture;
Step 5: add pH adjusting agent in above-mentioned stirred vessel;
Step 6: add purified water in stirred vessel, is stirred into emulsifiable paste;
Step 7: after homogenizing, fill.
10. a kind of pharmaceutical composition containing lignocaine, prilocaine according to claim 3,4 or 5, is characterized in that this pharmaceutical composition is preparing the application in anaesthetic.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201510118390.7A CN104688717A (en) | 2015-03-18 | 2015-03-18 | Drug combination containing lidocaine and prilocainum |
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| Application Number | Priority Date | Filing Date | Title |
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| CN201510118390.7A CN104688717A (en) | 2015-03-18 | 2015-03-18 | Drug combination containing lidocaine and prilocainum |
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| CN108653446A (en) * | 2018-07-26 | 2018-10-16 | 四川大学华西医院 | A kind of surface anesthesia pharmaceutical composition, micro emulsion and its preparation method and application |
| WO2022100120A1 (en) * | 2020-11-11 | 2022-05-19 | 长沙晶易医药科技有限公司 | External preparation of lidocaine-prilocaine pharmaceutical composition and application thereof |
| CN113975261A (en) * | 2021-12-06 | 2022-01-28 | 郑州大学第一附属医院 | Combined medicinal cream for anesthesia and preparation method thereof |
| CN113975261B (en) * | 2021-12-06 | 2023-02-17 | 郑州大学第一附属医院 | Combined medicinal cream for anesthesia and preparation method thereof |
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