CN101249152B - Preparing method of low toxicity aconitum analgesia preparation - Google Patents

Abstract

The invention discloses a preparation method of a low toxic aconite analgesia preparation. Taking TCM Crude Sichuan aconite root and Crude kusnezoff monkshood as raw ingredients, the preparation method adds NaOH in the raw ingredients based on the conventional aconitine extraction technology, so as to lead the high toxic diester type alkaloid to be thoroughly degraded into low toxic aconine combination and analgesic effects to be unchanged. The aconine class material obtained by the preparation method is processed into oral preparations such as troches, dropping pills, etc., the bioavailability is high, the toxicity is low, and the cost is low.

Description

A kind of preparation method of low toxicity aconitum analgesia preparation

Technical field

The present invention relates to a kind of manufacture method of aconitum analgesia preparation, be used for pharmaceuticals industry.

Background technology

Radix Aconiti is the dry parent root (main root) of ranunculaceae plant Aconitum carmichjaelii Debx. (Aconitum carmichaeli Debx.).Radix Aconiti is turbination, and the multidirectional side in middle part is expanded, the appearance sepia, and scattered have a tubercle shape lateral root, and matter is solid, acrid in the mouth and numb tongue.Radix Aconiti Preparata is irregular lamellar, crust pitchy, tangent plane grey black, visible polygon ring grain, lightly seasoned and not numb tongue or little numb tongue.Radix Aconiti Preparata is one of conventional Chinese medicine clinically.Effect with antalgic, expelling wind and removing dampness.Energy warming the meridian network, and, have very strong narcotic analgesic effect again with by ailment said due to cold or exposure, except that cold temperature.Radix Aconiti Kusnezoffii (Radix AconitiKusnezoffii) belongs to the dried root of cohosh Aconitum kusnezoffii Reichb, also has the effect of antalgic, expelling wind and removing dampness.

Very toxic because of Radix Aconiti, must can take orally through concocting processing, Radix Aconiti Kusnezoffii has the toxicity bigger than Radix Aconiti because of it, and Shang Weijian is used for clinical report.The toxic component of Radix Aconiti is mainly aconitine, and oral 0.2mg just makes us poisoning, and 3～4mg will poison the people with poison.And the toxic component of Radix Aconiti Kusnezoffii is the high molecular alkaloid of two esterifications such as benzoyl-Palmic acid or linoleic acid, so toxicity is bigger.

Tradition is concocted the Radix Aconiti method: get clean Radix Aconiti size separately, water or saturated limewater are dipped to the interior no dried heart, take out to add water boil 4～6h, only get the big individual solid person of reaching and cut the interior no white heart, when mouth is tasted little living numb feeling in the tongue, take out and coolly do to sixty percent, be drying to obtain the Radix Aconiti Preparata sheet.Its detoxifcation mechanism be Aconitum carmichjaelii Debx. in the immersion and boiling process of long period, hypertoxic aconitine is hydrolyzed into toxicity less even benzoyl aconine seldom and aconine.

This tradition concocting method has following defective:

1, lime water soak and decocting in water after, with the no white heart in cutting, it is quality control standard that mouth is tasted sense organ such as little living numb feeling in the tongue, has the incomplete probability of aconitine hydrolysis, also just has the danger of poisoning;

2, because of differences such as the places of origin of raw materials, trophophase and process of preparing Chinese medicine conditions, cause the uncertain of finished product mesaconitine, aconitine content, influence drug effect;

3, the soak that is abandoned in the concocting process contains mass efficient composition aconine, is the significant wastage to raw material.

Summary of the invention

For solving the defective that exists in traditional concocting method, the invention provides a kind of preparation method of low toxicity aconitum analgesia preparation, its technical scheme of taking is:

This preparation method adopts following processing step:

1) preparation of drug extract:

1. get Radix Aconiti or Radix Aconiti Kusnezoffii, pulverize the NaOH-alcoholic solution lixiviate of back, keep water temperature, reflux or supersound extraction 6-8 hour at 80-90 ℃ with 0.1mol/L;

2. the filtering residue that obtains after filtering is used the NaOH-alcoholic solution lixiviate twice of 0.1mol/L again, keeps water temperature at 80-90 ℃, reflux or supersound extraction 6-8 hour;

3. after the filtrate that 1. 2. obtains with step by step merges, at first reclaim ethanol to there not being the alcohol flavor, transfer PH to arrive neutrality then, the gained concentrated solution is the drug extract of aconine compounds;

4. concentrated solution at first extracts with chloroform, merges to obtain organic facies, uses anhydrous magnesium sulfate drying then, after the filtration filtrate is used the Rotary Evaporators evaporate to dryness, thereby obtains the crystal of Aconitum carmichjaelii Debx. total alkaloids;

2) tablet or drop pill preparation

According to the conventional preparation method of tablet or drop pill, in crystal, add substrate and mix, tabletting or make drop pill.

Concentration of ethanol can be controlled in 10%-95% in the NaOH-alcoholic solution.

The beneficial effect that the present invention had is:

1, with the lixiviate of NaOH-alcoholic solution, 80-90 ℃ of hot reflux or supersound extraction make Aconitum carmichjaelii Debx. in the immersion and boiling process of long period, and the aconitine of severe toxicity is hydrolyzed into toxicity less even benzoyl aconine seldom and aconine;

2, take the lixiviating solution that contains mass efficient composition aconine, improved the bioavailability of medical material;

3, purification and quantitatively aconine, replacing traditional sense organ is quality control standard, improves the accuracy and the safety of dosage.

The specific embodiment

Below in conjunction with embodiment the present invention is described further.

Embodiment one:

1. take by weighing Mount Taishan and produce Radix Aconiti Kusnezoffii 100g, pulverize in the 500ml round-bottomed flask of packing into, add the NaOH-95% ethanol 300ml of 0.1mol/L, then round-bottomed flask is placed in the water-bath, install reflux, keep water temperature at 85 ℃, 6 hours after-filtration are extracted in hot reflux;

2. the filtering residue that obtains after filtering is used the NaOH-95% alcoholic solution lixiviate twice of 0.1mol/L again, keeps water temperature at 85 ℃, reflux or supersound extraction 6 hours;

3. after the filtrate that obtains by step 1 and step 2 merges,, reclaim ethanol, transfer PH to neutral with hydrochloric acid then, the about 20ml of gained concentrated solution to there not being the alcohol flavor at the Rotary Evaporators concentrating under reduced pressure;

4. extract with 30mL * 3 chloroforms, merge and to obtain organic facies, use anhydrous magnesium sulfate drying, after the filtration filtrate used the Rotary Evaporators evaporate to dryness, thereby obtain the crystal of Aconitum carmichjaelii Debx. total alkaloids;

5. according to the preparation method of conventional tablet or drop pill, in crystal, add substrate and mix, tabletting or make drop pill.

Crystal is weighed, and the 100g Radix Aconiti Kusnezoffii obtains the thick Aconitum carmichjaelii Debx. total alkaloids of 1.15g, and yield is 1.15%; Crystal is carried out LC-MS analysis (mass spectrum is seen Fig. 1), can conclude that according to mass spectrum product is an aconine;

Embodiment two:

1. take by weighing commercially available Radix Aconiti Kusnezoffii 100g, in the 500ml beaker of packing into after the pulverizing, add the NaOH-10% ethanol 300ml of 0.1mol/L, then beaker is put in the ultrasonic leaching device, keep water temperature, filter 85 ℃ of lixiviates 6 hours;

2. the filtering residue that obtains after filtering is used the NaOH-95% alcoholic solution lixiviate twice of 0.1mol/L again, keeps water temperature at 85 ℃, reflux or supersound extraction 6 hours;

3. after the filtrate that obtains by step 1 and step 2 merges,, reclaim ethanol, transfer PH to neutral with hydrochloric acid then, the about 20ml of gained concentrated solution to there not being the alcohol flavor at the Rotary Evaporators concentrating under reduced pressure;

4. extract with 30mL * 3 chloroforms, merging obtains organic facies, uses anhydrous magnesium sulfate drying, filters, and filtrate is used the Rotary Evaporators evaporate to dryness, thereby obtain the crystal of Aconitum carmichjaelii Debx. total alkaloids;

5. according to the preparation method of conventional tablet or drop pill, in crystal, add substrate and mix, tabletting or make drop pill.

Crystal is weighed, and the 100g Radix Aconiti Kusnezoffii obtains the thick Aconitum carmichjaelii Debx. total alkaloids of 0.95g, and yield is 0.95%; Crystal is carried out LC-MS analysis (mass spectrum is seen Fig. 2), can conclude that according to mass spectrum product is an aconine.

Description of drawings

Fig. 1 is the M/Z200-1000 scope scanning mass spectrum of Mount Taishan of the present invention aconine that Radix Aconiti Kusnezoffii is put forward;

Fig. 2 is the M/Z400-1000 scope scanning mass spectrum of aconine that commercially available Radix Aconiti Kusnezoffii is put forward.

Claims (2)

1. the preparation method of a low toxicity aconitum analgesia preparation is characterized in that adopting following processing step:

1) preparation of drug extract:

1. get Radix Aconiti or Radix Aconiti Kusnezoffii, pulverize the NaOH-alcoholic solution lixiviate of back, keep water temperature, reflux or supersound extraction 6-8 hour at 80-90 ℃ with 0.1mol/L;

2. the filtering residue that obtains after filtering is used the NaOH-alcoholic solution lixiviate twice of 0.1mol/L again, keeps water temperature at 80-90 ℃, reflux or supersound extraction 6-8 hour;

3. after the filtrate that 1. 2. obtains with step by step merges, at first reclaim ethanol to there not being the alcohol flavor, transfer PH to arrive neutrality then, the gained concentrated solution is the drug extract of aconine compounds;

4. concentrated solution at first extracts with chloroform, merges to obtain organic facies, uses anhydrous magnesium sulfate drying then, after the filtration filtrate is used the Rotary Evaporators evaporate to dryness, thereby obtains the crystal of Aconitum carmichjaelii Debx. total alkaloids;

2) tablet or drop pill preparation

According to the conventional preparation method of tablet or drop pill, in crystal, add substrate and mix, tabletting or make drop pill.

2. the preparation method of a kind of low toxicity aconitum analgesia preparation according to claim 1, it is characterized in that: the concentration of ethanol scope is 10%-95% in the NaOH-alcoholic solution.

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