Novel Process for Extraction of Piperine

[pHarmacist]

Piperine:



Abstract:

The present invention relates to a process for extraction of piperine from the fruits of Piper species, comprising the steps of: contacting the fruit of piper species with aqueous hydrotrope solution at a temperature in the range of 0-100 C. and separating the solution from the solid residue by known methods, and recovering piperine from the solution by known methods.

Previous methods for separation of piperine:

H. Staudinger and H. Schnieider [Ber; 56, 699(1923)] described a process for the extraction of piperine from Piper nigrum fruits, wherein the alkaloid was extracted using ethanol and the extract was treated with aqueous sodium hydroxide to remove all the resinous matter. Other solvents used for extraction are petroleum ether and dichloromethane. The extraction of piperine into these organic solvents is not selective as other compounds like gums, polysaccharides and resins are extracted reducing the purity of piperine. The post extraction processing to purify piperine is cumbersome and uneconomical. A liquid pepper composition containing pepper in a concentrated form has been prepared by extracting the pepper fruits with acetone and subsequent treatment with anhydrous lactic acid (Wealth of India, Raw Materials, Vol. III, pg. 111).

Vidal, J. P. and Richard, H., (Scientific .Aliments 1987, 7(3), 481-98) outlines a procedure for the production of black pepper oleoresins by dense carbon dioxide extraction or carbon dioxide+ethanol extraction. The extract contains 16.7% essential oils and 42.2% piperine which was very close to that obtained by dichloromethane as solvent.

Hans J. (3,706594 German. Offen. DE 28/02/1987, Beutler) described a process wherein gaseous carbon dioxide under supercritical conditions is passed downward through a packed bed of pulverised pepper and the loaded solvent is then expanded in a downstream separator for release of the extracted material. However, this process using supercritical fluid extraction is not economical and still a further solvent extraction step is essential for obtaining pure piperine.

Most of these prior art processes relate to the extraction of Piper nigrum oleoresin containing piperine and other volatile oils. Piperine containing oleoresin is then solvent extracted and recrystallised to obtain pure piperine. These conventional processes are carried out using a number of steps which often present difficult operating conditions and result in a high cost of production.


Summary of Present Invention:

The invention provides a novel two-step process for the extraction of piperine from plants of piper species using aqueous hydrotrope solution.


Chemicals Used:
 
* Piper nigrum (Dried fruits of black pepper)
* Sodium butyl glycol sulphate (50% aqueous solution, Hulls Germany)
* Sodium n-butyl benzene sulphonate salt (synthesised in the laboratory)
* Sodium cumene sulphonate (Navdeep Chemicals Pvt.Ltd.)
* Sodium xylene sulphonate (Navdeep Chemicals Pvt.Ltd.)
* Sodium p-toluene sulphonate(Navdeep Chemicals Pvt.Ltd)
* Dichloromethane (AR grade)
* Methanol (HPLC grade)
* Method of Analysis: High Performance Liquid Chromatography with C18 reverse phase column.

EXAMPLE 1

Whole pepper 20 gms was pulverised to a coarse powder of mesh size# 6 and was added to 100 ml aqueous sodium butyl glycol sulfate of 2.5 gmol/lit concentration and the suspension was stirred vigorously for 2 hours at 30 DEG C. The solution was filtered and then diluted by addition of 310 ml waterThe precipitated piperine was dried and analysed for purity. The recovery of piperine was 58.8% (716 mg.) based on the amount of piperine present in the dried fruit with a purity of 98%.

EXAMPLE 2

Whole pepper 20 gms was pulverised to a coarse powder of mesh size# 6 and added to 100 ml aqueous sodium butyl glycol sulfate 2.5 of gmol/lit concentration and the suspension was stirred vigorously for 2 hours at 80 DEG C. The solution was filtered and then diluted three times by addition of 310 ml water. The precipitated piperine was dried and then dissolved in dichloromethane and analysed for purity. The recovery of piperine was 56.38% (687 mg.) based on the amount of piperine present in the dried fruit with a purity of 89%.

EXAMPLE 3

Whole pepper 20 gms was pulverised to a coarse powder of mesh size# 6 and added to 100 ml aqueous sodium n-butyl benzene sulfonate of 1.0 gmol/lit concentration and the suspension was stirred vigorously for 2 hours at 30 DEG C. The solution was filtered and then diluted by the addition of 2000 ml of water. The precipitated piperine was separated by centrifugation, dried and then dissolved in dichloromethane and analysed for purity. The recovery of piperine was 63.92% (0.76 g.) based on the amount of piperine present in the dried fruit with a purity of 97.4%.

EXAMPLE 4

Whole pepper 20 gms was pulverised to a coarse powder of mesh size# 6 and added to 100 ml aqueous sodium n-butyl benzene sulfonate of 2.0 gmol/lit concentration and the suspension was stirred vigorously for 2 hours at 30 DEG C. The solution was filtered and then diluted by addition of 2000 ml. of water. The precipitated piperine was separated by centrifugation, dried and then dissolved in dichloromethane and analysed for purity. The recovery of piperine was 95.75% (1.14 g.) based on the amount of piperine present in the dried fruit with a purity of 93%.

EXAMPLE 5

Whole pepper 20 gms was pulverised to a coarse powder of mesh size# 72 and added to 100 ml aqueous sodium n-butyl benzene sulfonate of 2.0 gmol/lit concentration and the suspension was stirred vigorously for 2 hours at 30 DEG C. The solution was filtered and then diluted by addition of 2000 ml of water. The precipitated piperine was separated by centrifugation, dried and then dissolved in dichloromethane and analysed for purity. The recovery of piperine was 92.14% (1.095 g.) based on the amount of piperine present in the dried fruit with a purity of 90.15%.

EXAMPLE 6

Whole pepper 20 gms was pulverised to a coarse powder of mesh size #300 and added to 100 ml aqueous sodium n-butyl benzene sulfonate 2.0 gmol/lit concentration and the suspension was stirred vigorously for 2 hours at 30 DEG C. The solution was filtered and then diluted by addition of 2000 ml water. The precipitated piperine was separated by centrifugation, dried and then dissolved in dichloromethane and analysed for purity. The recovery of piperine was 90.14% (1.07 g.) based on the amount of piperine present in the dried fruit with a purity of 89.14%.

EXAMPLE 7

Whole pepper 20 gms was pulverised to a coarse powder of mesh size# 6 and was added to 100 ml aqueous sodium n-butyl benzene sulfonate of 2.0 gmol/lit concentration and was stirred vigorously for 2 hours at 30 DEG C. The solution was filtered and then extracted with 50 ml. dichloromethane three times. The recovered piperine was analysed for purity. The recovery of piperine was 96.82% (1.15 g.) based on the amount of piperine present in the dried fruit with a purity of 95.13%.

EXAMPLE 8

Whole pepper 20 gms was pulverised to a coarse powder of mesh size# 6 and added to 100 ml of aqueous sodium xylene sulfonate 2.0 gmol/lit concentration and was stirred vigorously for 2 hours at 30 DEG C. The solution was filtered and then diluted by addition of 2000 ml water. The precipitated piperine was separated by centrifugation, dried and then dissolved in dichloromethane and analysed for purity. The recovery of piperine was 65.43% (0.77 g.) based on the amount of piperine present in the dried fruit with a purity of 60.41%.

EXAMPLE 9

Whole pepper 20 gms was pulverised to a coarse powder of mesh size# 6 and added to 100 ml of aqueous sodium cumene sulfonate 2.0 gmol/lit concentration and was stirred vigorously for 2 hours at 30 DEG C. The solution was filtered and then diluted by addition of 2000 ml water. The precipitated piperine was separated by centrifugation, dried and then dissolved in dichloromethane and analysed for purity. The recovery of piperine was 72.3% (0.85 g.) based on the amount of piperine present in the dried fruit with a purity of 68.00%.

EXAMPLE 10

Whole pepper 20 gms was pulverised to a coarse powder of mesh size# 6 and added to 100 ml aqueous sodium p-toluene sulfonate of 2.0 gmol/lit concentration and the suspension was stirred vigorously for 2 hours at 30 DEG C. The solution was filtered and then diluted by addition of 2000 ml water. The precipitated piperine was separated by centrifugation, dried and then dissolved in dichloromethane and analysed for purity. The recovery of piperine was 49% (0.582 g.) based on the amount of piperine present in the dried fruit with a purity of 52.3%.

Refernece:

Patent US6365601

"Turn on, Tune in and Drop Out"

[foxy2]

Here is an alternative method of extracting piperine.

They can never take away Piperine and therefore Piperonal.
foxy


Solubilized oleoresin black pepper, method of making same, and method of adding same to chewing gum

Patent US5087458

Oleoresin black pepper is an extract of pepper produced by extracting piperine, volatile oils and fixed oils from dried pepper pods by using a solvent, such as ethylene dichloride or acetone. After extraction, the solvent is removed, as by distillation, and there remains an extract of pepper known as oleoresin black pepper. The oleoresin black pepper is an unstable paste-like composition which, upon standing, separates into two phases. As a result of its instability, oleoresin black pepper is difficult to utilize in the manufacture of compositions that require its presence. By solubilizing the oleoresin black pepper into a stable, free-flowing, liquid oleoresin composition, the oleoresin black pepper becomes much easier to handle when used in various manufacturing processes. Unfortunately, oleoresin black pepper is very difficult to solubilize. The only solvent available for solubilizing oleoresin black pepper, prior to the discovery of the present invention, was benzyl alcohol. See U.S. Pat. No. 4,409,257.


Use of piperine as a bioavailability enhancer

Patent US5744161

Example 14
A preparation obtained in a unique manufacturing process.

Commercially available Black pepper oleoresin or Long pepper oleoresin is used as the source of piperine. Ground up Black pepper or Long pepper can also be used.

To a mixture of butanol and hexane (35 liters), 35 kg Black pepper oleoresin is added and heated to 40.degree. C. The mixture is then cooled and filtered. The precipitate is washed with Butanol/hexane mixture to obtain crude piperine.

The crude piperine is dissolved in methanol at 60.degree. C. and treated with alumina and charcoal by stirring. It is then filtered and concentrated under vacuum to obtain a powder.
Bioperine.RTM.

Material thus prepared has the following specifications: Color: Pale yellow crystalline powder
Melting range: 128 degrees-131 degrees Celsius
Assay: min. 98% pure piperine (by HPLC)


Process for making high purity piperine for nutritional use

Patent US6054585

Example
A process to recover piperine from resin of black pepper.

A reaction vessel was charged with 0.9 kg of urea, 3.7 kg of ethanol or 2.7 kg of methanol and 0.3 kg of the resin of black pepper to form a mixture. The mixture was refluxed for approximately one hour. The refluxed mixture was cooled overnight to a temperature of 0.degree. to 5.degree. C. The cooled mixture was then filtered to remove solids (e.g. wax, urea, fatty acids). The filtrate was then concentrated to obtain 180 g of piperine and some unreacted urea. The 180 g of piperine was recrystallized by adding ethanol. The piperine crystals were collected by filtration and dried to yield approximately 75 g of 98% pure piperine.


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Isolation of Natural Piperine (I)
Grind fresh peppercorns (25 g) to a fine powder, place in a Soxhlet thimble, and extract with
ethanol (100 mL) for 90 minutes. Cool the resulting solution, filter if necessary, and concentrate on
the rotary evaporator. Keep the water bath below 60 °C during the concentration. Dissolve the
residue in 10 % alcoholic potassium hydroxide (25 mL). Decant the solution if any residue re-
mains. Cool the solution in an ice bath, and add water dropwise (about 30 ml will be required) to
precipitate the piperine. Collect the piperine on a sintered glass funnel, and dry it on the vacuum
pump. If time allows, a recrystallization from acetone:hexanes (3:2) will produce cleaner material.
Record the mp, ir and 1 H nmr spectrum of piperine.

http://www.chemistry.uvic.ca/chem465-66/465e03piperine.pdf

Piperine Home Page

http://web1.caryacademy.org/chemistry/rushin/StudentProjects/CompoundWebSites/2000/Piperine/piperin_home_page.htm

[Rhodium]

Most of the above can already be found in 3base's excellent archive:

https://www.thevespiary.org/rhodium/Rhodium/chemistry/3base/piperonal.pepper/