PROCESS FOR THE PREPARATION OF BAKUCHIOL COMPOSITION SUBSTANTIALLY FREE OF FURANOCOUMARIN IMPURITIES

Abstract

The present invention relates to a process for preparation of Bakuchiol enriched psoralea extract substantially free of furanocoumarin impurities such as psoralen, isopsoralen and Bakuchicin and composition comprising the same. The process of the present invention uses unpulverized seeds of Psoralea genus of plants such as Psoralea corylifolia and employs novel single column chromatographic separation technique comprising silica gel and aluminium oxide columns clubbed to form single column to obtain a bakuchiol composition which is substantially free of furanocoumarin impurities. The bakuchiol composition is effective for prevention, alleviation, reduction, or treatment of post inflammatory hyper pigmentation (PIH) without any side-effects such as potential phototoxicity, topical irritation, carcinogenicity, and reproductive toxicity associated with furanocoumarin impurities.

Claims

1. A method for the preparation of a composition comprising Bakuchiol that is substantially free of furanocoumarin impurities said method comprising the steps of: a. Extracting unpulverized seeds of Psoralea genus of plants with petroleum ether through ultrasonication technique; b. Purifying extract obtained in step (a) by single column chromatographic separation technique comprising of silica gel and aluminium oxide columns clubbed into a single column to obtain a bakuchiol composition which is free of furanocoumarin impurities.

2. The method for the preparation of a composition comprising Bakuchiol as claimed in claim 1 wherein the plant is Psoralea corylifolia Linn.

3. The method for the preparation of a composition comprising Bakuchiol as claimed in claim 1 wherein the time for extraction in step (a) is in the range from 15 to 45 min.

4. The method for the preparation of a composition comprising Bakuchiol as claimed in claim 1 wherein the purity of Bakuchiol is not less than 99% with impurity profile not more than 20.0 ppm.

5. A Bakuchiol composition substantially free of furanocoumarin impurities such as Psoralen, Isopsoralen and Bakuchicin.

6. The Bakuchiol composition as claimed in claim 5 wherein the purity of Bakuchiol is not less than 99.0% and Assay of the main ingredient Bakuchiol by HPLC is also not less than 99.0%.

7. The Bakuchiol composition as claimed in claim 5 contains Bakuchiol with a purity 99.90% and Assay of the main ingredient Bakuchiol by HPLC is also not less than 99.0% and furanocoumarin impurities limit was not more than 20.0 ppm and the said Bakuchiol composition is free from Additives and Excipients.

8. The Bakuchiol composition as claimed in claim 7 wherein the Assay limit is not less than 99.0%.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0050] The following description is provided to assist in a comprehensive understanding of exemplary embodiments of the invention. It includes various specific details to assist in that understanding but these are to be regarded as merely exemplary.

[0051] Features that are described and/or illustrated with respect to one embodiment may be used in the same way or in a similar way in one or more other embodiments and/or in combination with or instead of the features of the other embodiments.

[0052] The present invention relates to process for preparation of Bakuchiol enriched psoralea extract essentially free of furanocoumarin impurities such as psoralen, isopsoralen and Bakuchicin. Thus, the potential phototoxicity, topical irritation, carcinogenicity, and reproductive toxicity associated with these compounds are essentially eliminated. The present invention more particularly relates to Bakuchiol compositions that is effective for prevention, alleviation, reduction, or treatment of post inflammatory hyper pigmentation (PIH).

[0053] “Prevention” in the context of the present invention refers to prophylactic methods which hinder or stop the occurrence of a particular condition, for example PIH.

[0054] “Alleviation” in the context of the present invention refers to lessening or mitigating the effects or symptoms of a particular condition, for example PIH.

[0055] “Reduction” in the context of the present invention refers to decreasing the effects or symptoms of a particular condition, for example PIH.

[0056] “Treatment” in the context of the present invention refers to techniques or methods intended to improve the symptoms of decrease or stop the occurrence of a particular condition, for example PIH.

[0057] “Impurity” includes any substance that is not desired in the bakuchiol composition, typically resulting from the isolation of bakuchiol from natural sources. The term impurity includes, but is not limited to furanocoumarin compounds including, but not limited to, psoralen, isopsoralen and other coumarin type impurities.

[0058] In an embodiment there is provided a method for the preparation of a composition comprising Bakuchiol that is substantially free of furanocoumarin impurities said method comprising the steps of: [0059] a. Extracting unpulverized seeds of Psoralea genus of plants with petroleum ether through ultrasonication technique; [0060] b. Purifying extract obtained in step (a) by single column chromatographic separation technique comprising silica gel and aluminium oxide columns clubbed into a single column to obtain a bakuchiol composition which is free of furanocoumarin impurities.

[0061] In another embodiment, the bakuchiol is extracted from Psoralea genus of plants, for example, Psoralea corylifolia L. (Luguminosae) or Psoralea glandulosa L. (Papilionaceae).

[0062] In a preferred embodiment Bakuchiol is extracted from seed of Psoralea corylifolia.

[0063] The purity of Bakuchiol obtained by the process of the present invention is not less than 99% and with impurity profile not more than 20.0 ppm.

[0064] In yet another embodiment there is provided a Bakuchiol enriched psoralea extract substantially free of furanocoumarin impurities such as Psoralen, Isopsoralen and Bakuchicin. The purity of Bakuchiol in the said extract is not less than 99% and content of impurity not more than 20.0 ppm.

Examples

[0065] The present invention will now be explained in detail by reference to the following formulation examples and a test example, which should not be construed as limiting the scope of the present invention.

[0066] Manufacturing Process:

[0067] Extraction:

[0068] In the Ultrasonication extraction of Psoralea corylifolia unpulverized seeds with PETROLEUM ETHER 60-80 extraction the content of Bakuchiol by HPLC will come around 65-67%, the Content of psoralene and angelicin will be 0.80% & 0.50%. In regular solvent extractions the limits will be 1.5-2.0%.

[0069] Initially we have processed with the coarse powder of P. corylifolia L. It was extracted with different solvents (ethanol, methanol, acetone, petroleum ether, and dichloromethane) in Raw material:solvent ratio of 1:10 volumes by ultrasonication method for 45 min with input power of 220 V and heating power of 550 W, equipped with time and temperature controller. The extracts obtained were concentrated under reduced pressure to obtain brownish colored viscous liquid. The extract was evaporated to dry to get brownish extract, which contains Bakuchiol by HPLC assay 28-30.0% Assay. That results almost same as regular extraction process.

[0070] After that we have invented a process which contains the unpulverized seeds extracted with a high-intensity probe system (Model: UIP2000dht) of 2000 W and 20 kHz from Heilscher Ultrasound Technology. Ultrasonic probe was immersed in a seed-solvent mixture. Raw material:solvent ratio of 1:4 volumes. Temperature was maintained between 40-60° C. Sample was treated with ultrasound power range 60-90% with amplitude 70-90% for 15 min. The extracts obtained were concentrated under reduced pressure to obtain light brownish colored viscous liquid. The extract was evaporated to dry to get a light brownish extract, which contains Bakuchiol by HPLC assay 65-68.0% Assay. That results almost double to the regular extraction process

[0071] The Time of Extraction and Volume of Solvents are as Follows:

[0072] Extraction: 4.0 Volumes of solvent to the raw material quantity and time of extraction maximum 15.0 minutes.

[0073] Total Extraction solvent volume will be 4.0 Volumes to the raw material quantity and total time consumption will be 15.0 minutes, with an output Assay 65-67% and % Yield 5.5-6.0 in a single extraction.

[0074] The extraction process of the present invention eliminates the 12.0 volumes of alcohol consumption and 7.0 volumes of Hexane consumption in the process and reduces the 30.0 hours of time cycle.

[0075] Purification:

[0076] The Novel Column chromatographic separation technique in the purification step is used in the present invention. The present inventors have clubbed the Silica Gel and Aluminium oxide columns in a single column in calculated proportions based on NLT 65% assay extracted material.

[0077] 65-67% assay paste on 1.5 volumes of silica Gel 100-200 #Mesh and chromatographed over 3.5 volumes of calculated proportionate of Silica Gel and Aluminum oxide as a separation column, the solvent used for the column was only 10.0 KL of Hexane and Ethyl acetate solvent re-circulated.

[0078] One single column with total 5.0 volumes of separation Silica Gel and Aluminum oxide reduces the 10.0 volumes of Silica Gel and 10.0 volumes of Aluminum oxide, which will be a great benefit for the environment, because the Silica Gel and Aluminum oxide are not reused products, both the products are effluents only. The process of the present invention reduces the effluent load.

[0079] In the present invention by using invented column process by taking Ultrasonic extracted material, an Assay of Bakuchiol NLT 99.0% with and impurity profile NMT 20.0 ppm is obtained [Content of Psoralene and Angelicin will be 2.0 ppm & 0.1 ppm]

[0080] The present invention reduces the huge alcohol use in extraction process as well as time of the process which includes pulverization, extraction, filtration and alcohol distillation which in turn reduces the energy consumption, manpower and working hours with better assay [67% Instead of 27%], and the product is free from Alcohol [Methanol/Ethanol] traces.

[0081] And in continuation the separation step also reduces the Silica Gel and Aluminum oxide quantities as well as solvent consumption, there is huge solvent consumption for older two column process which includes solvent distillation and loss etc. In single column process of the present invention the solvent consumption of solvent is reduced and higher assay with lesser impurity load is obtained.

EXAMPLES

[0082] The present invention will now be explained in detail by reference to the following examples which should not be construed as limiting the scope of the present invention.

Example 1

[0083] 1000.0 Kg Psoralea Corylifolia Linn unpulverized seeds were extracted with 4000.0 Ltrs Petroleum ether using a high-intensity probe system (Model: UIP2000dht) of 2000 W and 20 kHz from Heilscher Ultrasound Technology. Ultrasonic probe was immersed in a seed-solvent mixture, Temperature was maintained between 40-60° C. Sample was treated with ultrasound power range 60-90% with amplitude 70-90% for 15 min. [0084] The above extract was evaporated to dry to get a light brownish extract, weight 50.10 Kg, which contains Bakuchiol by HPLC assay 67.29% Assay and Content of Psoralene and Angelicin are 0.49% and 0.62% respectively. [0085] The 50.0 Kg crude light brown colored paste was adsorbed on 75.0 Kg of Silica gel 100-200 Mesh #, and chromatographed over the column contains a total 175.0 Kg of Silica gel and aluminium oxide. [0086] As per TLC, collected the Bakuchiol pure fractions and distilled of the fractions to get pure honey colored product Qty: 19.5 Kg with an Assay 99.20% and content of Psoralene and Angelicin are 0.02 ppm % & 0.01 ppm % respectively.

[0087] The product of the present invention [NeuvaChiol™ [Bakuchiol 99%]] contains Bakuchiol with a purity 99.90% and furanocoumarin impurities limit was NMT 20.0 ppm and this product is free from Additives/Excipients and the Assay limit was 99.0%. The Bakuchiol known product offer only 99.0% purity and their assay is NMT 90.0%. The product of the present invention have the Assay limit NLT 99.0%, % Moisture by KF [USP<921>1.0%] to make 100.0% composition.