CN1266685A - Process for preparing long-acting compound analgesic - Google Patents
Process for preparing long-acting compound analgesic Download PDFInfo
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- CN1266685A CN1266685A CN 00114359 CN00114359A CN1266685A CN 1266685 A CN1266685 A CN 1266685A CN 00114359 CN00114359 CN 00114359 CN 00114359 A CN00114359 A CN 00114359A CN 1266685 A CN1266685 A CN 1266685A
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Abstract
A process for preparing a long-acting compound analgesic includes such steps as proportionally weighing the recrystallized long-acting analgesic component and local anesthetic component, fully dissolving in water for injection, stirring, adding osmotic pressure regulator, antioxidizing agent and acid-alkali reagent, diluting with water for injection, regulating pH value, filtering, pouring, and sterilization. Its advantages are long acting up to one month, convenient application, high safety, low cost and stable quality.
Description
The present invention relates to a kind of technical matters method of long-acting composite analgesic preparation of product, it belongs to the medicine and pharmacology technical field, also belongs to technical field of chemistry.For a long time, because human to various diseases institute algesiogenic cause of disease understanding limitation, particularly the therapeutic outcome of persistent pain is not satisfied to various pain to make people.At present, the most frequently used clinically analgesic is divided into two big classes: a class is non-steroidal anti-inflammatory medicine (NSAID); Another kind of is the opiates anti-inflammatory agent.Because various chronic, all necessary long-term heavy dose of medications of persistent pain, so, non-steroidal anti-inflammatory class medicine life-time service can cause many untoward reaction such as gastrointestinal reaction, gastric ulcer, gastrorrhagia and allergy; Opiates anti-inflammatory drug life-time service has addiction and is limited the use of in accordance with the law.
Methylene blue is the twentieth century medicine of the fifties with regard to using clinically, and the intravenous injection of methylene blue injection is used for the rescue of cyanide poisoning and nitrite poisoning.And domestic and foreign literature has also been reported the otherwise application of methylene blue, as oral methylene blue treatment urinary system calculus; The treatment periodontitis; And the reported in literature of the therapeutical effect relevant with the present invention also publishes in succession.For example, adopt methylene blue and procaine system to be made into compound recipe solution partial closure treatment neurodermatitis [Chen Xinqian etc., " new pharmacology " (14 editions), People's Health Publisher (1998)]; Adopt methylene blue, Daphne giraldii Nitsche and tetracaine compound recipe solution to be used for operation on anus pain relieving [Ren Chuanpao " Chinese Medical Journal " 1997 (2) 158]; The composite solution that adopts methylene blue, dexamethasone, vitamin B12 to form is used for 50 example treatment trigeminal neuralgias [Cao suckle treasure's " Clinical Anaesthesiology magazine " 1992 (8) 2 119].
Although the report of existing methylene blue analgesic effect in the document, but reported in literature only is the clinicist uses commercially available separately methylene blue injection and the interim compatibility of other drug, composition (ratio, concentration), preparing technique process, quality control, the animal test of pesticide effectiveness for the analgesic prescription are all studied, just the small test technical result of " experimental stage " can't be directly used in suitability for industrialized production.And, the technology of these reported in literature, the dilution administration also exists the uncertainty of bringing " secondary pollution ", analgesic concentration and the unstability (being the unstability of drug quality) of analgesic compound recipe solution compatibility of drugs before clinical use.
The objective of the invention is:, intend proposing containing the product that methylene blue in the analgesic of methylene blue produces the optimum concentration range of human body of analgesic effect and be convenient to suitability for industrialized production and form and the technical matters method in order to overcome the problem that above-mentioned analgesic exists; Dilute the secondary pollution that administration may bring before also will avoiding, overcome clinical use, and plan is explored the stability of component concentration, ratio when solving two kinds of compatibility of drugss of analgesic, make the analgesic constant product quality, but in the hope of reaching analgesic that local location uses hold time long, no addiction, and can alleviate the pain that diseases such as pain that the caused pain of performing the operation, treatment of traumatic pain, gingivitis causes and hemorrhoid complicated by anal fistula cause.In addition, technical matters method of the present invention answers raw material to be easy to get, not have special reagent, uncomplicated, the easy operating of technical matters method in preparation, and the product cost price is relatively low, is easy to carry out industrial-scale production.
Be the technical measures that realize that the object of the invention is taked:
Analgesic of the present invention prepares used methylene blue raw material to be needed can use after the assay was approved through refining.Process for purification is: with the methylene blue recrystallization, after the oven dry, the internal control quality standard of working out by the present invention can use after the assay was approved.
Methylene blue and one or more local anesthetics that the present invention will make with extra care after qualified are prepared into a kind of composite injection stable formulation, the position is done to soak into or the retardance drug administration by injection around pain, utilize methylene blue and nervous tissue that the characteristics of strong affinity are arranged, reversibility blocking-up peripheral nerve is to the susceptibility of pain, reach the purpose of analgesia sensation, by the consumption of control methylene blue, its analgesic effect was maintained about a couple of days to one month.
Local anesthetic is except that lignocaine, and also alternative use tetracaine or procaine or bupivacaine also can use by multiple local anesthetic simultaneously.
The concentration range of the contained methylene blue of analgesic of the present invention is 0.05%～2.0%; The concentration range of one or more in the local anesthetic is 0.05%～5.0%.
The technical matters method of analgesic preparation of the present invention is: will make with extra care methylene blue after the assay was approved, after the water for injection dissolving that uniform temperature is arranged, join and use in the dissolved local anesthesia drug solns of water for injection, the limit edged stirs, and behind the mixing, adds the additional additives that comprises osmotic pressure regulator, pH value regulator, antioxidant by consumption 0.1%～2.0% respectively, the pH value of regulator solution is between 3.0-7.0, after filtration, be sub-packed in and in, promptly obtain the analgesic product after the sterilization.
Additional additives has: the reagent of regulating osmotic pressure is that sodium chloride is or/and glucose; The reagent of regulating pH value is acid-base reagents such as hydrochloric acid or sodium hydroxide; The antioxidant that increases analgesic stability is sodium sulfite or sodium metabisulfite etc.
The method of quality control of analgesic of the present invention, it is to adopt high performance liquid chromatography (HPLC) method, mobile phase is the acetonitrile solution that contains acetate buffer.Immobile phase is a silica gel chromatographic column.This can measure the content of this analgesic component effectively, is an effective analysis test method to control, assurance analgesic product quality.
Compared with the prior art, the technique effect that reached of the present invention:
Analgesic of the present invention, through toxicological study institute of Wuhan Tongji Medical Univ. " toxicity, pharmacological testing ", this analgesic adopts electrostimulation and hot plate method through in accordance with regulations animal experiment, proves to have analgesic activity at 30 days; 1 minute onset time, effectively held time this product safety, irritated, the non-toxic reaction of nothing 30 days.Methylene blue has reversibility to the effect of peripheral nerve.Show through animal experiment and clinical practice, not only keep analgesic time length and do not have addiction.
This analgesic can use at part, the caused pain of disease such as pain that pain, treatment of traumatic pain, the gingivitis that can alleviate performs the operation causes causes and hemorrhoid complicated by anal fistula.It is stable that the component of the analgesic product that is prepared into is formed concentration ratio, and product quality is also just stable, and the control of product quality detection method of science is arranged.Because constant product quality, analgesic effect duration can be more than 2 years.Simultaneously, can not produce secondary pollution in the production yet.When using clinically, medical personnel do not need to face with preceding solubilizer dilution or dosing, can increase or reduce the capacity of administration according to the situation of pain degree, time and position size, thereby make things convenient for the clinical medical and nursing personnel to use, and are beneficial to individual administration yet.
In the technical matters method of this analgesic preparation of product, its methylene blue and local anesthetic raw material, reagent and other additional additives are easy to get, do not need special reagent in the preparation, so cost is lower, and operational approach is simple, handle easy, industrial-scale production analgesic product easy to implement, all enterprise, factories that possesses the injection working condition all can produce this analgesic product.
Embodiment:
Take by weighing methylene blue 20 grams, dissolve it with 80 ℃ of waters for injection; Other takes by weighing lignocaine 100 grams, dissolve it with 80 ℃ of waters for injection, methylene blue solution and lignocaine solution are mixed, and be stirred to mix homogeneously, in composite solution, add 2% glucose solution 20ML then, add 0.1mol/L hydrochloric acid solution 2ML, the pH value to 5.5 of regulator solution adds the injection water again, make liquor capacity to 1000ML, after filtration, filtrate is carried out packing, after sterilization, promptly obtain analgesic injection product.
Claims (3)
1. the technical matters method of a long-acting composite analgesics preparation of product, it is characterized in that: in methylene blue: local anesthetic=0.05-2: the 0.05-5 ratio is dissolved the methylene blue of recrystallization with water for injection, in addition will comprise that any one or more local anesthetic of tetracaine, lignocaine, procaine, bupivacaine dissolves with water for injection, two kinds of solution mix homogeneously under agitation; Add osmotic pressure regulator respectively, regulate the acid-base reagent that comprises hydrochloric acid or sodium hydroxide that pH value uses, the antioxidant that increases the pH stability of medicine by 0.1-0.2% then, be diluted to certain volume with water for injection, the pH value to 3.0 of regulator solution is between 7.0, packing is after filtering also sterilized, and promptly obtains the analgesic product.
2. by the described technical matters method of claim 1, it is characterized in that: additional additives is the reagent that comprises the adjusting osmotic pressure of sodium chloride, glucose; Regulate the composite solution pH value with the acid-base reagent that comprises hydrochloric acid, sodium hydroxide; Increase analgesic stability with the antioxidant that comprises sodium sulfite, sodium metabisulfite.
3. by the described technical matters method of claim 1, it is characterized in that: adopt high performance liquid chromatography control analgesic product quality, its mobile phase is the acetonitrile solution that contains acetate buffer, and immobile phase is a silicagel column, adopts external standard method content.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 00114359 CN1266685A (en) | 2000-01-29 | 2000-01-29 | Process for preparing long-acting compound analgesic |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 00114359 CN1266685A (en) | 2000-01-29 | 2000-01-29 | Process for preparing long-acting compound analgesic |
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| CN1266685A true CN1266685A (en) | 2000-09-20 |
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| CN 00114359 Pending CN1266685A (en) | 2000-01-29 | 2000-01-29 | Process for preparing long-acting compound analgesic |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103239456A (en) * | 2013-04-26 | 2013-08-14 | 临江市妇幼保健院 | Pharmaceutical composition for easing pain and use thereof |
| CN103393714A (en) * | 2013-08-20 | 2013-11-20 | 李赴朝 | Local anesthesia pain-relieving time-delay agent |
-
2000
- 2000-01-29 CN CN 00114359 patent/CN1266685A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103239456A (en) * | 2013-04-26 | 2013-08-14 | 临江市妇幼保健院 | Pharmaceutical composition for easing pain and use thereof |
| CN103393714A (en) * | 2013-08-20 | 2013-11-20 | 李赴朝 | Local anesthesia pain-relieving time-delay agent |
| WO2015024420A1 (en) * | 2013-08-20 | 2015-02-26 | Li Fuchao | Local anesthesia pain-relieving time-delay agent |
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