CN103908463A - Lincomycin hydrochloride gel and preparation process thereof - Google Patents
Lincomycin hydrochloride gel and preparation process thereof Download PDFInfo
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- CN103908463A CN103908463A CN201410170731.0A CN201410170731A CN103908463A CN 103908463 A CN103908463 A CN 103908463A CN 201410170731 A CN201410170731 A CN 201410170731A CN 103908463 A CN103908463 A CN 103908463A
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- hydrochloride
- lincomycin
- lidocaine hydrochloride
- lidocaine
- gel
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Abstract
The invention discloses lincomycin hydrochloride gel and a preparation process thereof. Lincomycin hydrochloride and lidocaine hydrochloride are used as main drugs of the gel, oleic macrogolglyceride is used as a permeation enhancer, caprylic capric triglyceride is used as a surfactant, and octanoate decanoate macrogolglyceride is used as an oil solvent. The preparation process of the preparation disclosed by the invention is simple, no special storage condition is needed, the product stability is good, and more importantly, the transdermal permeability of the lidocaine hydrochloride is improved, so as to further improve the efficacy.
Description
technical field
The invention belongs to technical field of medicine, in particular to a kind of external medicine preparation that contains lincomycin hydrochloride and lidocaine hydrochloride.
Background technology
The various skin infections that lincomycin hydrochloride and lidocaine hydrochloride gel causes for minor burn, wound and mosquito bite.Lincomycin hydrochloride (lincomycin) is antibiotic, and antimicrobial spectrum is similar to erythromycin, mainly gram positive bacteria is had to higher antibacterial activity, and its mechanism of action is to suppress bacterium protein to synthesize.Lignocaine is local anesthetic, and external has pain relieving, itching-relieving action; Lidocaine hydrochloride is the amide-type local anesthetic of commonly using clinically, has anesthetic action feature fast and strong and that timeliness is long, is a kind of desirable local anesthetic.
Gel is preparation capable of permeating skin, and the transdermal enhancer of use mainly contains azone, propylene glycol, carbamide, Mentholum etc.But above-mentioned transdermal enhancer is lower to the skin transmitance of drug salts lidocaine hydrochloride, as the mixing transdermal enhancer of 5% propylene glycol, 5% carbamide and 0.5% Mentholum composition only has 9.74% to the utilization rate of lignocaine cataplasma Chinese medicine; The mixing transdermal enhancer of 15% propylene glycol, 5% carbamide and 1% Mentholum composition only has 2.23% (Liu Tingting etc. to the utilization rate of lignocaine cataplasma Chinese medicine; The impact of different penetrating agents on lidocaine hydrochloride cataplasma transdermal; Journal of Chinese Hospital Pharmacy, 2008,28 (3): 198-200), azone is to only 2.06% (Zhang Feng etc. of the utilization rate of lignocaine in lignocaine spray; The impact of laurocapram on transdermal permeation of lidocaine in lignocaine spray; Medicine Leader, 2010,29 (1): 31-33).
CN102370613B discloses a kind of lidocaine gel agent, and in said preparation, transdermal enhancer is made up of mango butter and menthol.Due to the synergism of mango butter and menthol, higher to the transdermal efficiency of lidocaine hydrochloride, be up to 17.09%.But menthol easily distils, need avoid high temperature, therefore lidocaine gel agent is for a long time or after accelerating to investigate, skin permeation rate declines.
Summary of the invention
In view of the deficiencies in the prior art, technical problem to be solved by this invention is how to improve the transdermal penetration rate of lidocaine hydrochloride.Inventor considers that microemulsion can improve drug osmotic rate, but regrettably, even if be prepared into microemulsion, the permeability of lignocaine is only up to 21.3%.Further, inventor considers it may is the problem of penetrating agent, and inventor, through lot of experiments research, is surprised to find that while adopting oleic acid polyethyleneglycol glyceride as transdermal enhancer, skin permeation rate obviously increases.
Based on above research, the object of the invention is to by prescription and technique are improved, thereby a kind of lincomycin hydrochloride and lidocaine hydrochloride gel agent that can effectively improve lidocaine hydrochloride skin transmitance is provided.
The object of the present invention is achieved like this:
A kind of lincomycin hydrochloride and lidocaine hydrochloride gel agent, described gel is take lincomycin hydrochloride and lidocaine hydrochloride as principal agent, take oleic acid polyethyleneglycol glyceride as transdermal enhancer, take Miglyol 812N as surfactant, take Labraso as oil solvent.
Preferably, lincomycin hydrochloride and lidocaine hydrochloride gel agent as above, wherein said gel is prepared from by lincomycin hydrochloride, lidocaine hydrochloride, oleic acid polyethyleneglycol glyceride, Miglyol 812N, Labraso and xanthan gum solution.
Further preferably, lincomycin hydrochloride and lidocaine hydrochloride gel agent as above, wherein said gel is prepared from by following mass percent by lincomycin hydrochloride, lidocaine hydrochloride, oleic acid polyethyleneglycol glyceride, Miglyol 812N, Labraso and xanthan gum solution:
Lincomycin hydrochloride 0.5%
Lidocaine hydrochloride 0.4%
Oleic acid polyethyleneglycol glyceride 5-15%
Miglyol 812N 10-30%
Labraso 20-30%
Xanthan gum solution surplus.
Again further preferably, lincomycin hydrochloride and lidocaine hydrochloride gel agent as above, wherein said gel is prepared from by following mass percent by lincomycin hydrochloride, lidocaine hydrochloride, oleic acid polyethyleneglycol glyceride, Miglyol 812N, Labraso and xanthan gum solution:
Lincomycin hydrochloride 0.5%
Lidocaine hydrochloride 0.4%
Oleic acid polyethyleneglycol glyceride 7.5-12%
Miglyol 812N 16-22%
Labraso 23-26%
Xanthan gum solution surplus.
Lincomycin hydrochloride and lidocaine hydrochloride gel agent of the present invention, the concentration of wherein said xanthan gum solution is 5%-10%(W/V).Further preferably, the concentration of xanthan gum solution as above is 7%(W/V).
The present invention also provides the preparation technology of above-mentioned lincomycin hydrochloride and lidocaine hydrochloride gel agent, and this technique comprises the steps:
(1) lincomycin hydrochloride and lidocaine hydrochloride are joined in xanthan gum solution, be stirred to dissolve, obtain settled solution, for subsequent use as water;
(2) take oleic acid polyethyleneglycol glyceride, Miglyol 812N, add in Labraso, stir, obtain settled solution, for subsequent use as oil phase;
(3) oil phase is joined in water, stir, obtain lincomycin hydrochloride and lidocaine hydrochloride gel.
Compared with prior art, the lincomycin hydrochloride and lidocaine hydrochloride gel agent preparation technology who the present invention relates to is simple, and without particular storage condition, product stability is good, is easy to industrialized great production.The more important thing is, increased substantially the transdermal penetration rate of lidocaine hydrochloride, thereby further improved drug effect.
The specific embodiment
Now further describe preparation process of the present invention and implementation result by following examples, embodiment is only for the object of illustration, do not limit the scope of the invention, within the apparent change that those of ordinary skills make according to the present invention simultaneously and modification are also contained in the scope of the invention.
the preparation of embodiment 1 lincomycin hydrochloride and lidocaine hydrochloride gel
lincomycin hydrochloride 0.5%
Lidocaine hydrochloride 0.4%
Oleic acid polyethyleneglycol glyceride 5.8%
Miglyol 812N 20%
Labraso 20%
5% xanthan gum solution surplus.
Preparation technology:
(1) lincomycin hydrochloride, lidocaine hydrochloride are joined to 5%(W/V) xanthan gum solution in, be stirred to dissolve, obtain settled solution, for subsequent use as water;
(2) take oleic acid polyethyleneglycol glyceride, Miglyol 812N, add in Labraso, stir, obtain settled solution, for subsequent use as oil phase;
(3) oil phase is joined in water, stir, obtain lincomycin hydrochloride and lidocaine hydrochloride gel.
the preparation of embodiment 2 lincomycin hydrochloride and lidocaine hydrochloride gels
lincomycin hydrochloride 0.5%
Lidocaine hydrochloride 0.4%
Oleic acid polyethyleneglycol glyceride 13.1%
Miglyol 812N 27%
Labraso 30%
10% xanthan gum solution surplus.
Preparation technology:
(1) lincomycin hydrochloride, lidocaine hydrochloride are joined to 10%(W/V) xanthan gum solution in, be stirred to dissolve, obtain settled solution, for subsequent use as water;
(2) take oleic acid polyethyleneglycol glyceride, Miglyol 812N, add in Labraso, stir, obtain settled solution, for subsequent use as oil phase;
(3) oil phase is joined in water, stir, obtain lincomycin hydrochloride and lidocaine hydrochloride gel.
the preparation of embodiment 3 lincomycin hydrochloride and lidocaine hydrochloride gels
lincomycin hydrochloride 0.5%
Lidocaine hydrochloride 0.4%
Oleic acid polyethyleneglycol glyceride 10%
Miglyol 812N 18%
Labraso 24%
7% xanthan gum solution surplus.
(1) lincomycin hydrochloride, lidocaine hydrochloride are joined to 7%(W/V) xanthan gum solution in, be stirred to dissolve, obtain settled solution, for subsequent use as water;
(2) take oleic acid polyethyleneglycol glyceride, Miglyol 812N, add in Labraso, stir, obtain settled solution, for subsequent use as oil phase;
(3) oil phase is joined in water, stir, obtain lincomycin hydrochloride and lidocaine hydrochloride gel.
comparative example 1 does not add penetrating agent oleic acid polyethyleneglycol glyceride
lincomycin hydrochloride 0.5%
Lidocaine hydrochloride 0.4%
Miglyol 812N 18%
Labraso 24%
7% xanthan gum solution surplus.
Preparation technology:
(1) lincomycin hydrochloride, lidocaine hydrochloride are joined to 7%(W/V) xanthan gum solution in, be stirred to dissolve, obtain settled solution, for subsequent use as water;
(2) take Miglyol 812N, add in Labraso, stir, obtain settled solution, for subsequent use as oil phase;
(3) oil phase is joined in water, stir, obtain lincomycin hydrochloride and lidocaine hydrochloride gel.
comparative example 2 adopts carbamide to replace oleic acid polyethyleneglycol glyceride as penetrating agent
lincomycin hydrochloride 0.5%
Lidocaine hydrochloride 0.4%
Carbamide 10%
Miglyol 812N 18%
Labraso 24%
7% xanthan gum solution surplus.
(1) lincomycin hydrochloride, lidocaine hydrochloride, carbamide are joined to 7%(W/V) xanthan gum solution in, be stirred to dissolve, obtain settled solution, for subsequent use as water;
(2) take Miglyol 812N, add in Labraso, stir, obtain settled solution, for subsequent use as oil phase;
(3) oil phase is joined in water, stir, obtain lincomycin hydrochloride and lidocaine hydrochloride gel.
comparative example 3 adopts azone to replace oleic acid polyethyleneglycol glyceride as penetrating agent
lincomycin hydrochloride 0.5%
Lidocaine hydrochloride 0.4%
Azone 10%
Miglyol 812N 18%
Labraso 24%
7% xanthan gum solution surplus.
(1) lincomycin hydrochloride, lidocaine hydrochloride are joined to 7%(W/V) xanthan gum solution in, be stirred to dissolve, obtain settled solution, for subsequent use as water;
(2) take azone, Miglyol 812N, add in Labraso, stir, obtain settled solution, for subsequent use as oil phase;
(3) oil phase is joined in water, stir, obtain lincomycin hydrochloride and lidocaine hydrochloride gel.
the preparation of comparative example's 4 lidocaine hydrochloride ointments
Lidocaine hydrochloride 4g
Triethanolamine 0.2g
Ethyl hydroxybenzoate 0.1g
Mango butter 6g
Menthol 2g
Glyceryl monostearate 2g
Liquid paraffin 4g
Vaseline 1g
Lanoline 4g
Water 60g
Preparation method:
(1) take mango butter, menthol, glyceryl monostearate, liquid paraffin, vaseline and lanoline, be heated to 80 ℃ of mixed meltings, make oil phase;
(2) under the condition of 75 ℃, take triethanolamine, lidocaine hydrochloride and ethyl hydroxybenzoate, soluble in water, make water;
(3) water of step (2) is poured in the oil phase of step (1), after stirring, made Lidocaine hydrochloride transdermal ointment.
the transdermal penetration rate determination experiment of embodiment 4 medicines
In the non-jacket layer diffusion cell of improved Franz, carry out Transdermal Absorption experiment.The fresh depilation abdominal part Corium Mus of peeling off is fixed between two Room diffusion cells, stratum corneum side is to supply pool, corium is towards acceptance pool, and the ointment that contains transdermal enhancer of 0.5g is spread upon above the horny layer of Corium Mus equably, process after 20 minutes, wipe the corresponding ointment containing transdermal enhancer.Setting water temperature in temperature chamber is 37 ± 0.1 ℃, in acceptance pool, adds 7 milliliters of corresponding acceptable solutions, and acceptable solution is normal saline, puts into the preheating body outer osmotic disperser temperature chamber of 30 minutes, and setting acceptance pool mixing speed is 100 revolutions per seconds.In supply pool, add lincomycin hydrochloride and lidocaine hydrochloride gel agent, carry out In vitro penetration test.After 12h, measure the content of lidocaine hydrochloride in absorption cell.Drug level in sample liquid adopts HPLC method to detect.
The mensuration of drug level.Employing high performance liquid chromatography detects.Chromatographic condition: adopt YWG C18 chromatographic column (250mm × 4.6mm, 5 μ m), phosphate buffer (is got the sodium dihydrogen phosphate 1.3ml of 1mol/L and the disodium phosphate soln 32.5ml of 0.5mol/l, be placed in the volumetric flask of 1000ml, be diluted with water to scale, shake up, adjusting pH value with phosphoric acid is 8.0)-acetonitrile (50: 50); Detect wavelength 254nm; Flow velocity 1.0ml/min; 30 ℃ of column temperatures; Sample size 10 μ l.Adopt the method for peak area to measure drug level.
In the sample of sampling, the accumulation transmitance S (%) of lidocaine hydrochloride calculates according to the following formula: S=(7 × C)/(5% × W × 1000) × 100%; Wherein, the concentration (μ g/ml) of acceptable solution Chinese medicine when C is sampling, W is lidocaine hydrochloride jelly agent drug loading (g).Result of the test is as shown in table 1.
The transdermal penetration rate measurement result of the each embodiment sample of table 1
Known according to the result of the test of table 1, prepared by embodiment of the present invention 1-3 product, its lidocaine hydrochloride permeability is high, and after accelerated test, permeability is without significant change; Comparative example 1 does not add penetrating agent oleic acid polyethyleneglycol glyceride, and comparative example 2 and comparative example 3 adopt respectively carbamide, azone to replace oleic acid polyethyleneglycol glyceride as penetrating agent, but its effect is undesirable; Comparative example 4 adopts prior art to prepare ointment, and permeability is lower than the present invention, and after accelerating because of menthol distillation, permeability obviously declines.
Claims (7)
1. a lincomycin hydrochloride and lidocaine hydrochloride gel agent, it is characterized in that: described gel is take lincomycin hydrochloride and lidocaine hydrochloride as principal agent, take oleic acid polyethyleneglycol glyceride as transdermal enhancer, take Miglyol 812N as surfactant, take Labraso as oil solvent.
2. lincomycin hydrochloride and lidocaine hydrochloride gel agent according to claim 1, is characterized in that: described gel is prepared from by lincomycin hydrochloride, lidocaine hydrochloride, oleic acid polyethyleneglycol glyceride, Miglyol 812N, Labraso and xanthan gum solution.
3. lincomycin hydrochloride and lidocaine hydrochloride gel agent according to claim 2, is characterized in that: described gel is prepared from by following mass percent by lincomycin hydrochloride, lidocaine hydrochloride, oleic acid polyethyleneglycol glyceride, Miglyol 812N, Labraso and xanthan gum solution:
Lincomycin hydrochloride 0.5%
Lidocaine hydrochloride 0.4%
Oleic acid polyethyleneglycol glyceride 5-15%
Miglyol 812N 10-30%
Labraso 20-30%
Xanthan gum solution surplus.
4. lincomycin hydrochloride and lidocaine hydrochloride gel agent according to claim 3, is characterized in that: described gel is prepared from by following mass percent by lincomycin hydrochloride, lidocaine hydrochloride, oleic acid polyethyleneglycol glyceride, Miglyol 812N, Labraso and xanthan gum solution:
Lincomycin hydrochloride 0.5%
Lidocaine hydrochloride 0.4%
Oleic acid polyethyleneglycol glyceride 7.5-12%
Miglyol 812N 16-22%
Labraso 23-26%
Xanthan gum solution surplus.
5. according to the lincomycin hydrochloride and lidocaine hydrochloride gel agent described in claim 2-4 any one, it is characterized in that: the concentration of described xanthan gum solution is 5%-10%(W/V).
6. lincomycin hydrochloride and lidocaine hydrochloride gel agent according to claim 5, is characterized in that: the concentration of described xanthan gum solution is 7%(W/V).
7. according to a preparation technology for the lincomycin hydrochloride and lidocaine hydrochloride gel agent described in claim 2-4 any one, it is characterized in that this technique comprises the steps:
(1) lincomycin hydrochloride and lidocaine hydrochloride are joined in xanthan gum solution, be stirred to dissolve, obtain settled solution, for subsequent use as water;
(2) take oleic acid polyethyleneglycol glyceride, Miglyol 812N, add in Labraso, stir, obtain settled solution, for subsequent use as oil phase;
(3) oil phase is joined in water, stir, obtain lincomycin hydrochloride and lidocaine hydrochloride gel.
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| CN201410170731.0A CN103908463B (en) | 2014-04-27 | 2014-04-27 | A kind of lincomycin hydrochloride and lidocaine hydrochloride gel agent and preparation technology thereof |
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| CN201410170731.0A CN103908463B (en) | 2014-04-27 | 2014-04-27 | A kind of lincomycin hydrochloride and lidocaine hydrochloride gel agent and preparation technology thereof |
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| CN103908463B CN103908463B (en) | 2016-06-15 |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112220789A (en) * | 2020-11-10 | 2021-01-15 | 马保臣 | Compound lidocaine gel for pets, and preparation method and quality control method thereof |
| CN112494507A (en) * | 2020-12-23 | 2021-03-16 | 上海新亚药业闵行有限公司 | Lincomycin lidocaine gel and preparation method thereof |
-
2014
- 2014-04-27 CN CN201410170731.0A patent/CN103908463B/en not_active Expired - Fee Related
Non-Patent Citations (4)
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| YANG, JAE-HEON 等: "Transdermal delivery and analgesic effects of lidocaine hydrogel by phonophoresis", 《KOREAN SOCIETY OF PHARMACEUTICAL SCIENCES AND TECHNOLOGY》, vol. 37, no. 3, 31 December 2007 (2007-12-31), pages 149 - 158 * |
| 余小平: "高效液相法测定林可霉素利多卡因凝胶中盐酸利多卡因的含量", 《浙江中西部科技论坛》, 31 December 2005 (2005-12-31), pages 197 * |
| 徐颖颖 等: "促渗剂对利多卡因凝胶透皮作用的影响", 《中国药房》, vol. 14, no. 6, 31 December 2003 (2003-12-31), pages 337 - 338 * |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112220789A (en) * | 2020-11-10 | 2021-01-15 | 马保臣 | Compound lidocaine gel for pets, and preparation method and quality control method thereof |
| CN112494507A (en) * | 2020-12-23 | 2021-03-16 | 上海新亚药业闵行有限公司 | Lincomycin lidocaine gel and preparation method thereof |
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| CN103908463B (en) | 2016-06-15 |
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Inventor after: Wang Dunliang Inventor before: Zhang Defang |
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Effective date of registration: 20160519 Address after: 266034 Shandong province Qingdao City, Tong Fu Road No. 6 Qingdao city hospital for women and children Applicant after: Wang Dunliang Address before: Baoji City, Shaanxi Province Dongfeng Road 721000 District 45 No. Third Hospital of PLA Applicant before: Bai Lingqiang |
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