CN102846610A - Local externally-applied antalgic compound preparation composition for skin and preparation method thereof - Google Patents
Local externally-applied antalgic compound preparation composition for skin and preparation method thereof Download PDFInfo
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- CN102846610A CN102846610A CN2012103497623A CN201210349762A CN102846610A CN 102846610 A CN102846610 A CN 102846610A CN 2012103497623 A CN2012103497623 A CN 2012103497623A CN 201210349762 A CN201210349762 A CN 201210349762A CN 102846610 A CN102846610 A CN 102846610A
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Abstract
The invention relates to local externally-applied antalgic compound preparation composition for skin and a preparation method of the compound preparation composition. The compound preparation composition comprises the following components: (a) lidocaine hydrochloride; (b) ropivacaine hydrochloride monohydrate and conventional pharmaceutic adjuvant. The invention further relates to the preparation method of the compound preparation composition, which comprises the following steps of: mixing the lidocaine hydrochloride and the ropivacaine hydrochloride monohydrate through a conventional technological way and the conventional pharmaceutic adjuvant, and carrying out split charging to obtain the compound preparation composition. According to the compound preparation composition and the preparation method, the effect is significant, the efficacy time is long, the side effect is reduced, and the compliance of the patients is improved, so that the pain of the patients is alleviated. The compound preparation method composition provided by the invention can be applied to the pains caused by various factors, and has a good application prospect.
Description
Technical field
The present invention relates to medical technical field, specifically, a kind of local skin external application analgesic compound preparation composition and method of making the same that relates to.
Background technology
Local pain is behind clinical modal a kind of local operation or post-traumatic pain, loses neuropathic pain etc. after mainly comprising local pain that skin wound pain, injection or puncture cause and herpes zoster.Because the clinical nursing activity amount is large, does not cause numerous medical personnel's attention for local pain to the misery that the patient brings.Adopt local anesthetic percutaneous dosing treatment local pain to obtain clinically good result, as (grace is received frost to adopt compound lidocaine emulsifiable paste, Emlacream, every gram cream contains prilocaine and lignocaine is 25mg), stablize neurocyte by blocking the neural impulse generation and conducting required ion flow, reach the topical pain relief effect thereby produce the local anesthesia effect, but two kinds of medicines all belong to middle effect class local anesthetic in this compound recipe, analgesic activity is held time and is fallen short of.
Lidocaine hydrochloride (Lidocaine Hydrochloride) is to imitate local anesthetic in the most frequently used amide-type, by suppressing neuron membrane Na
+Interior stream and stablize neuron membrane stops the conduction of the generation of nerve action potential and impulsion and reaches analgesic effect, has rapid-action, the characteristics such as penetration power strong, skin good absorbing.At present existing lidocaine hydrochloride emulsifiable paste [Yali Zhu, Sheng Guorong. compound lidocaine emulsifiable paste external safety testing. pharmacy and clinical research, 2011; 19(5): 475-477], lidocaine hydrochloride jelly [Zhao Yu, An Xuemei, Liu Pihong, etc. lidocaine gel is smeared and is added hot compression therapy injectivity phlebitis observation of curative effect. contemporary medical science, 2009; The research of the external preparation report such as 15(28): 140].
Ropivacaine HCL (Ropivacaine Hydrochloride) is the long-acting local anesthetic of novel amide-type, has that acting duration is long, cardiac toxicity is low, sensation-motion retardance separates and the characteristics such as peripheral blood vessel contraction, and it is more suitable for for analgesia.Have clinically at present its injection listing (Naropin, Naropin), also there is its gel to be used for research report [the Franz-Montan M of oral mucosal surface anesthesia, Silva AL, Cogo K, et al.Efficacy of 1% ropivacaine gel for topical anesthesia of human oral mucosa.Quintessence Int, 2007; 38 (7): 601-6].
But, there is no at present the compound preparation compositions research of lidocaine hydrochloride and Ropivacaine HCL, also have no the external preparation research report that other contain middle effect class local anesthetic, long-acting class local anesthetic simultaneously.
Summary of the invention
The present invention is directed to the deficiency that above-mentioned prior art exists, a kind of compound preparation composition and method of making the same of local skin external application analgesic is provided.Effect of the present invention is remarkable, and effective drug duration is long, has reduced side effect, has improved patient's compliance, thereby has reduced patient's misery, and the present invention can be used for the pain that various factors causes, has a good application prospect.
The present invention is achieved through the following technical solutions,
The present invention relates to a kind of local skin external application analgesic compound preparation compositions, described compositions comprises following each component:
(a) lidocaine hydrochloride,
(b) Ropivacaine HCL,
And conventional pharmaceutic adjuvant.
Preferably, the weight ratio of described lidocaine hydrochloride and described Ropivacaine HCL is (0.25～25): 1.
Preferably, the weight ratio of described lidocaine hydrochloride and Ropivacaine HCL is 5:2.
Preferably, the weight ratio of described lidocaine hydrochloride and Ropivacaine HCL is 1:1.
Preferably, the dosage form of described compound preparation compositions is varnish, ointment, gel or thermosensitive hydrogel agent.
Second aspect the invention still further relates to the preparation method of aforementioned local skin external application analgesic compound preparation compositions, comprises the steps: to get lidocaine hydrochloride and Ropivacaine HCL, adopts routine techniques means and conventional pharmaceutic adjuvant mixed processing, packing, and get final product.
Compared with prior art, the beneficial effect that the present invention has is: local skin external application analgesic compound preparation compositions of the present invention, the Ropivacaine HCL that lidocaine hydrochloride in the employing in the effect class local anesthetic can rise in drug effect characteristics and the long-acting class local anesthetic fast can be kept combining of the long characteristics of effective drug duration, effect of the present invention is remarkable, effective drug duration is long, reduced side effect, improved patient's compliance, thereby reduced patient's misery, the present invention can be used for the pain that various factors causes, has a good application prospect.
The specific embodiment
The invention will be further described for following instance.The present embodiment carries out under take technical solution of the present invention as prerequisite, has provided detailed embodiment and process.Although with reference to preferred embodiment the present invention is had been described in detail; it will be understood by those skilled in the art that; still can make amendment or the part technical characterictic is equal to replacement the specific embodiment of the present invention; and not breaking away from the spirit of technical solution of the present invention, it all should be encompassed in the technical scheme scope that the present invention asks for protection.
Embodiment 1,The preparation of externally used compound varnish and compliance test result thereof
The present embodiment relates to a kind of local skin external application analgesic compound preparation compositions, and its preparation method comprises the steps: to take by weighing lidocaine hydrochloride 50g, Ropivacaine HCL 2g and is dissolved in an amount of purified water; Other gets sodium carboxymethyl cellulose 20g and swells in an amount of hot purified water, adds glycerol 50g, carbamide 100g dissolving and 5% ethyl hydroxybenzoate alcoholic solution 10g; Two liquid are merged, add purified water to full dose 1000g, stir evenly, end product externally used compound varnish is remembered in packing.
Sodium carboxymethyl cellulose (CMC-Na) can increase the denseness of varnish in the externally used compound varnish of the present embodiment, is conducive to prolong drug action time; Glycerol has moisture-keeping function, can reduce skin irritation; Carbamide can horny layer softening, is conducive to the dermal osmosis of medicine; Ethyl hydroxybenzoate is antiseptic, can prevent that preparation from going mouldy; Each composition consumption obtains through orthogonal design optimization in the prescription.
Implementation result: see Table 1.Adopt the topical pain relief effect of Mus tail tenderness method the effects medicine: get the adult female mice of Kunming kind, body weight 18～22g, at first mark apart from tail point 1/3 place at mouse tail, in the mark tenderness, survey the front Basic Pain Threshold value of administration with YLS-3E electronics tenderness instrument; Be divided at random blank varnish matched group, lidocaine hydrochloride varnish group, Ropivacaine HCL varnish group and compound recipe varnish group (n=10) by the basic tenderness threshold of pain and body weight, respectively at mouse tail mark coating, and behind coating, measure respectively pain threshold when 30min, 240min.
Lidocaine hydrochloride varnish, Ropivacaine HCL varnish and compound recipe varnish all have increasing action to the mouse skin threshold of pain, with blank varnish matched group comparing difference significance (P＜0.05) are arranged, and wherein increase the threshold of pain with compound recipe varnish group the most remarkable.
Table 1
| Group | 30min pain threshold (g) | 240min pain threshold (g) |
| Blank varnish matched group | 234.37±56.07 | 233.41±55.35 |
| Lidocaine hydrochloride varnish group | 341.11±61.75 | 294.32±51.75 |
| Ropivacaine HCL varnish group | 240.43±53.59 | 250.23±55.93 |
| Compound recipe varnish group | 350.70±62.00 | 308.70±58.00 |
Embodiment 2,The preparation of externally used compound emulsifiable paste and compliance test result thereof
The present embodiment relates to a kind of local skin external application analgesic compound preparation compositions, and its preparation method comprises the steps: to take by weighing lidocaine hydrochloride 20g, Ropivacaine HCL 20g, glycerol 50g and sodium lauryl sulphate 10g and is dissolved in the hot purified water of 600g (70 ℃) getting water; Other gets white vaseline 140g, octadecanol 80g, liquid Paraffin 60g, azone 20g and ethyl hydroxybenzoate 1g and puts and be heated to 70 ℃ in the water-bath, melts to get oil phase; Water is added in the oil phase in constantly stirring, note stirring to same direction, until fully emulsifying adds purified water to full dose 1000g, stir evenly, packing namely gets end product externally used compound emulsifiable paste.
Glycerol is wetting agent in the externally used compound emulsifiable paste of the present embodiment, can reduce skin irritation; Sodium lauryl sulphate is emulsifying agent, and made O/W type substrate is being stablized in the pH scope widely; White vaseline, octadecanol and liquid Paraffin consist of oil phase; Azone is skin absorption promoter, can promote the dermal osmosis of medicine; Ethyl hydroxybenzoate is antiseptic, can prevent that preparation from going mouldy; Each composition consumption obtains through orthogonal design optimization in the prescription.
Implementation result: see Table 2.Adopt the topical pain relief effect of Mus tail tenderness method the effects medicine: get the adult female mice of Kunming kind, body weight 18～22g, at first mark apart from tail point 1/3 place at mouse tail, in the mark tenderness, survey the front Basic Pain Threshold value of administration with YLS-3E electronics tenderness instrument; Be divided at random blank varnish matched group, lidocaine hydrochloride varnish group, Ropivacaine HCL varnish group and compound recipe varnish group (n=10) by the basic tenderness threshold of pain and body weight, respectively at mouse tail mark coating, and behind coating, measure respectively pain threshold when 30min, 240min.
Lidocaine hydrochloride emulsifiable paste, Ropivacaine HCL emulsifiable paste and compound cream all have increasing action to the mouse skin threshold of pain, with blank emulsifiable paste matched group comparing difference significance (P＜0.05) are arranged, and wherein increase the threshold of pain with the compound cream group the most remarkable.
Table 2
| Group | 30min pain threshold (g) | 240min pain threshold (g) |
| Blank emulsifiable paste matched group | 229.37±51.07 | 230.13±55.25 |
| Lidocaine hydrochloride emulsifiable paste group | 320.11±57.51 | 258.42±53.75 |
| Ropivacaine HCL emulsifiable paste group | 270.34±55.38 | 320.41±58.49 |
| The compound cream group | 338.70±61.30 | 341.70±62.00 |
Embodiment 3,The preparation of externally applied compound gel and compliance test result thereof
The present embodiment relates to a kind of local skin external application analgesic compound preparation compositions, and its preparation method comprises the steps: that taking by weighing lidocaine hydrochloride 5g, Ropivacaine HCL 20g by prescription is dissolved in an amount of purified water; Other gets carbopol (Carbomer-940) 10g and swells in an amount of hot purified water, adds glycerol 50g, azone 20g and 5% ethyl hydroxybenzoate alcoholic solution 6g; Two liquid are merged, regulate pH to 6.0 with triethanolamine, add purified water to full dose 1000g, stir evenly, packing namely gets the end product externally applied compound gel.
Carbomer-940 is as the host material of gel in the externally applied compound gel of the present embodiment, and viscosity is best when the near neutrality of pH; Glycerol has moisture-keeping function, can reduce skin irritation; Azone can promote the dermal osmosis of medicine as dermal osmosis accelerator; Ethyl hydroxybenzoate is antiseptic, can prevent that preparation from going mouldy; Triethanolamine has the pH regulator effect; Each composition consumption obtains through orthogonal design optimization in the prescription.
Implementation result: see Table 3.Adopt the topical pain relief effect of Mus tail tenderness method the effects medicine: get the adult female mice of Kunming kind, body weight 18～22g, at first mark apart from tail point 1/3 place at mouse tail, in the mark tenderness, survey the front Basic Pain Threshold value of administration with YLS-3E electronics tenderness instrument; Be divided at random blank varnish matched group, lidocaine hydrochloride varnish group, Ropivacaine HCL varnish group and compound recipe varnish group (n=10) by the basic tenderness threshold of pain and body weight, respectively at mouse tail mark coating, and behind coating, measure respectively pain threshold when 30min, 240min.
Lidocaine hydrochloride jelly, Ropivacaine HCL gel and compound gel all have increasing action to the mouse skin threshold of pain, with blank gel matched group comparing difference significance (P＜0.05) are arranged, and wherein increase the threshold of pain with the compound gel group the most remarkable.
Table 3
| Group | 30min pain threshold (g) | 240min pain threshold (g) |
| Blank gel matched group | 230.48±51.12 | 232.31±53.83 |
| The lidocaine hydrochloride jelly group | 240.61±54.63 | 238.32±53.25 |
| Ropivacaine HCL gel group | 271.40±55.26 | 318.32±56.50 |
| The compound gel group | 282.62±56.30 | 330.60±61.20 |
Embodiment 4,The preparation of externally used compound thermosensitive hydrogel and compliance test result thereof
The present embodiment relates to a kind of local skin external application analgesic compound preparation compositions, its preparation method comprise the steps: by prescription take by weighing lidocaine hydrochloride 50g, Ropivacaine HCL 20g, benzalkonium bromide 0.1g, PLURONICS F87 (German BASF AG) 5g are dissolved in an amount of purified water, poloxamer188 (German BASF AG) 160g is added to while stirring and is uniformly dispersed, add purified water to full dose 1000g, stir evenly, 4 ℃ in refrigerator is placed and obtained gelation temperature in 24 hours is 32 ℃ clear and bright solution, packing.
Poloxamer188 and PLURONICS F87 coupling are as the host material of thermosensitive hydrogel in the externally used compound thermosensitive hydrogel of the present embodiment, and temperature sensitive temperature is 32 ℃; Benzalkonium bromide is antiseptic, can prevent that preparation from going mouldy; Adopt cold process preparation technology; Each composition consumption obtains through orthogonal design optimization in the prescription.
Implementation result: see Table 4.Adopt the topical pain relief effect of Mus tail tenderness method the effects medicine: get the adult female mice of Kunming kind, body weight 18～22g, at first mark apart from tail point 1/3 place at mouse tail, in the mark tenderness, survey the front Basic Pain Threshold value of administration with YLS-3E electronics tenderness instrument; Be divided at random blank varnish matched group, lidocaine hydrochloride varnish group, Ropivacaine HCL varnish group and compound recipe varnish group (n=10) by the basic tenderness threshold of pain and body weight, respectively at mouse tail mark coating, and behind coating, measure respectively pain threshold when 30min, 240min.
Lidocaine hydrochloride thermosensitive hydrogel, Ropivacaine HCL thermosensitive hydrogel and compound temperature sensitive gel all have increasing action to the mouse skin threshold of pain, with blank thermosensitive hydrogel matched group comparing difference significance (P＜0.05) is arranged, wherein increase the threshold of pain with compound temperature sensitive gel group the most remarkable.
Table 4
| Group | 30min pain threshold (g) | 240min pain threshold (g) |
| Blank thermosensitive hydrogel matched group | 230.20±51.00 | 228.31±50.36 |
| Lidocaine hydrochloride thermosensitive hydrogel group | 342.00±61.25 | 290.30±51.00 |
| Ropivacaine HCL thermosensitive hydrogel group | 270.62±52.58 | 310.80±54.60 |
| Compound temperature sensitive gel group | 368.62±66.20 | 352.20±60.80 |
Embodiment 1～4 effect shows: lidocaine hydrochloride and Ropivacaine HCL form the externally used compound preparation compositions and have local synergic antalgic effect, and to select thermosensitive hydrogel be suitable as the dosage form of compound preparation compositions.In addition, this compound temperature sensitive gel is lost neuropathic pain behind clinical 40 example puncture patients, 20 routine herpes zoster on probation, and analgesia effect is remarkable, effective percentage 100%, no side effects.
In sum, local skin external application analgesic compound preparation compositions of the present invention, the Ropivacaine HCL that lidocaine hydrochloride in the employing in the effect class local anesthetic can rise in drug effect characteristics and the long-acting class local anesthetic fast can be kept combining of the long characteristics of effective drug duration, effect of the present invention is remarkable, and effective drug duration is long, has reduced side effect, improved patient's compliance, thereby reduced patient's misery, the present invention can be used for the pain that various factors causes, has a good application prospect.
Claims (6)
1. a local skin external application analgesic compound preparation compositions is characterized in that, described compositions comprises following each component:
(a) lidocaine hydrochloride,
(b) Ropivacaine HCL,
And conventional pharmaceutic adjuvant.
2. local skin external application analgesic compound preparation compositions as claimed in claim 1 is characterized in that, the weight ratio of described lidocaine hydrochloride and described Ropivacaine HCL is (0.25～25): 1.
3. local skin external application analgesic compound preparation compositions as claimed in claim 2 is characterized in that, the weight ratio of described lidocaine hydrochloride and Ropivacaine HCL is 5:2.
4. local skin external application analgesic compound preparation compositions as claimed in claim 2 is characterized in that, the weight ratio of described lidocaine hydrochloride and Ropivacaine HCL is 1:1.
5. local skin external application analgesic compound preparation compositions as claimed in claim 1 is characterized in that, the dosage form of described compound preparation compositions is varnish, ointment, gel or thermosensitive hydrogel agent.
6. method for preparing local skin external application analgesic compound preparation compositions as claimed in claim 1, it is characterized in that, comprise the steps: to get lidocaine hydrochloride and Ropivacaine HCL, adopt routine techniques means and conventional pharmaceutic adjuvant mixed processing, packing, and get final product.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN103816111A (en) * | 2014-02-26 | 2014-05-28 | 中国人民解放军第二军医大学 | Ropivacaine nanometer lipid carrier temperature-sensitive in-situ gel and preparation method thereof |
| CN104146954A (en) * | 2014-08-29 | 2014-11-19 | 广东埃纳生医疗投资发展有限公司 | Composite local anesthetic and preparation method of composite local anesthetic injection |
| CN113616796A (en) * | 2021-07-15 | 2021-11-09 | 江苏康禾生物制药有限公司 | Pain-relieving and anti-inflammatory compound sustained-release preparation |
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| CN101494976A (en) * | 2005-12-14 | 2009-07-29 | 扎尔斯制药公司 | Compositions and methods for dermally treating pain |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103816111A (en) * | 2014-02-26 | 2014-05-28 | 中国人民解放军第二军医大学 | Ropivacaine nanometer lipid carrier temperature-sensitive in-situ gel and preparation method thereof |
| CN103816111B (en) * | 2014-02-26 | 2016-08-17 | 中国人民解放军第二军医大学 | A kind of ropivacaine nano-lipid carrier temperature sensing in situ gel rubber and preparation method thereof |
| CN104146954A (en) * | 2014-08-29 | 2014-11-19 | 广东埃纳生医疗投资发展有限公司 | Composite local anesthetic and preparation method of composite local anesthetic injection |
| CN113616796A (en) * | 2021-07-15 | 2021-11-09 | 江苏康禾生物制药有限公司 | Pain-relieving and anti-inflammatory compound sustained-release preparation |
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