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THE PATENTS ACT, 1970 (39 of 1970)
&
THE PATENTS RULES, 2003 PROVISIONAL SPECIFICATION [See section 10, Rule 13]
DECOLORIZATION OF PROCESS STREAMS BY CHEMICAL OXIDATION IN THE MANUFACTURE OF TRICHLOROGALACTOSUCROSE:
PHARMED MEDICARE PVT. LTD., A COMPANY INCOPORATED UNDER THE COMPANIES ACT, 1956, WHOSE ADDRESS IS 141 WALCHAND HIRACHAND MARG, MUMBAI - 400 001, MAHARASHTRA, INDIA.
THE FOLLOWING SPECIFICATION DESCRIBES THE INVENTION.
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TECHNICAL FIELD
The present invention relates to decolorization treatment to a process stream during production of chlorinated sugars including 1'-6'-Dichloro-1'-6'-DIDEOXY-β-Fructofuranasyl-4-chloro-4-deoxy-galactopyranoside i.e. trichlorogalactosucrose (TGS) and its precursor (TGS-6-ester).
DESCRIPTION:
Majority of strategies used in prior art methods of production of 4,1', 6' trichlorogalactosucrose, the high intensity sweetener, abbreviated for the purpose of this specification as "TGS", also expressed as 1'-6'-Dichloro-1'-6'-DIDEOXY-β-Fructofuranasyl-4-chloro-4-deoxy-galactopyranoside, predominantly involve chlorination of 6-O-acyl sucrose by use of Vilsmeier-Haack reagent, to form 6 acyl 4,1', 6'trichlorogalactosucrose, using various chlorinating agents such as phosphorus oxychloride, oxalyl chloride, phosphorus pentachloride etc, and a tertiary amide such as dimethyl formamide (DMF). After the said chlorination reaction, the reaction mass is neutralized to pH 7.0 -7.5 using appropriate alkali hydroxides of calcium, sodium, etc. to deacylate / deacetylate the 6 acetyl 4,1', 6'trichlorogalactosucrose to form 4,1', 6' trichlorogalactosucrose.
The chlorinated mass after chlorination whether before or after deacylation is very dark in colour. This is due to a large number of decomposition products produced during the chlorination process. These compounds mostly are mixtures of caramel, furfurals etc. These compounds impart strong colour on the product and is very difficult to remove selectively by a particular adsorptive process such as carbon treatment etc.
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Individual components of the mixture of colour imparting compounds present in the chlorinated mass have a wide variety of properties, and some compounds have properties close to that of TGS. Therefore, these colour compounds move along with the purified TGS till the crystallization stage and imparts strong colour on the product crystallized. This results in reduced product purity and the final product specifications are not achieved.
During the purification of TGS by affinity chromatography, these colour compounds which have similar properties to that of TGS also binds along with TGS on to the resin and elute out along with the product. This results in reduction of the adsorptive capacity of the resin and is therefore undesirable.
The colouring compounds, which interfere during crystallization, must be removed by various treatment methods including but not limited to charcoal treatment and the like. In some cases, charcoal treatment is carried out repeatedly to obtain a colour free product.
A novel process of removing the colour from the Chlorinated mass or any other process stream in the purification cycle comprises subjecting the said stream to chemical oxidation process. This chemical oxidation process using ozone gas removes the colour from the process stream without subjecting the same to any kind of adsorptive methods. The Ozone gas is directly bubbled into the process stream and the decolourisation starts immediately. When the desired colour of the stream is achieved, it is then taken for the next purification stage. This method of decolourisation could be carried out at ambient temperature within a range of 5° to 60° celcius and at atmospheric pressure, does not require special conditions of temperature and pressure. . The method does not result in any product loss and the degree of decolourisation is achieved to highest possible
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extent when compared to any other known adsorptive colour removal which shall always carry away some product along with colour. However this chemical oxidation method does not degrade or carry away TGS with it.
The decolourised process stream when taken for isolation of TGS yields a product of high purity comprising a purity of 92 - 95 % and like in a single crystallization step without using any other adsorptive colour removal method such as charcoal treatment.
The colour reduction is measured in terms of Colour index Units abbreviated as CU measured on Platinum Cobalt Scale. The typical colour reduction is 6200 units per 1000 L in a time period of 4 -5 hrs with an Ozone gas bubbling rate at 100-120 g/hr. The gas bubbled as Ozone in the preferred process is a gas that effectively contains 7% to 14% of Ozone dissolved in Oxygen. This decolourisation is accompanied by reduction in pH of the solution and requires pH adjustment during Ozonization process.
The decolourisation step can be applied at one or more of a stage of TGS purification process including but not limited to the following :
1. Neutralized mass after chlorination containing 6-acetyl TGS with / without DMF.
2. Deacylated mass after chlorination containing TGS with / without DMF.
3. 6-acetyl TGS /TGS in an organic water immiscible solvent extract including one or more of ethyl acetate, methyl ethyl ketone, butyl acetate, methylene chloride, and the like.
4. 6-acetyl TGS/TGS in water.
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5. 6-acetyl TGS/TGS in water + a water miscible solvent including one or more of methanol, acetone and the like.
6. Any partially purified process stream, obtained in a process of preparation of TGS, containing hydrophilic or hydrophobic impurities.
7. A purified product stream prior to crystallization.
8. A crystallized product subjected to colour removal by re-dissolving in aqueous or organic solvent in which TGS/ 6-acetyl TGS is soluble.
9. Can be used in addition to any adsorptive colour removal not limited to charcoal treatment, resin treatment, etc.
10. Can be used for more than one time in the process
The description given in this specification as well as results given below are an account of summary of interim results on some of the preferred embodiments, which shall be improved upon by further work and fine tuned until complete specification is submitted. The details of work done so far disclosed below serve as illustrations and do not limit the scope of actual techniques used or scope of or range of reaction conditions or process conditions claimed. The techniques and reaction conditions or process conditions disclosed below are subject matter of ongoing trials and fine tuning or trials in alternative or better conditions. Several other adaptations of the embodiments will be easily anticipated by those skilled in this art and they are also included within the scope of this priority of subject matter covered by this specification. Throughout this specification, singular also encompasses its plural as well as one or more members of the same kind, unless context does not permit. Thus, "an organic solvent" encompasses also more than one organic solvent individually or as a mixture and could be any of the known organic solvent achieving same function or effect
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as described in the context of its use exemplified in the specification. Thus, mention of a 6-acetyl sucrose also encompasses in it one or more of a 6-acyl sucrose including 6-bezoyl sucrose, 6-acetyl sucrose, sucrose—6-phthalate, sucrose-6-propionate, sucrose-6-glutarate and the like.
In one experiment, 70 kg of 6-acetyl sucrose was chlorinated using the Vilsmeier-Haack Reagent generated from thionyl chloride.
386 kg of DMF was taken in a reactor and 16 kg of carbon was added to it. The mass was stirred and 300 kg of thionyl chloride was added dropwise keeping the temperature below 40°C. The mass was stirred for 60 minutes and then cooled to 0 - 5°C.
65 kg of 6-acetyl sucrose in DMF was added to the Vilsmeier reagent formed keeping the temperature below 5°C. After the addition, the reaction mass temperature was raised to room temperature maintained for 60 minutes.
Then the mass was heated to 85°C maintained for 60 minutes, heated again to 100°C maintained for 6 hrs and further heated to 115°C and maintained for 1.5 hrs.
The chlorinated mass containing 42% 6-acetyl TGS was then quenched with 1:1 calcium hydroxide slurry up to pH 7.0 and the mass was filtered through the filter press. The clear filtrate was then subjected to affinity chromatography using ADS 600 (Thermax India) resin. The filtered mass was passed through the resin bed filled in a column at 300 LPH and the 6-acetyl TGS and other chlorinated derivatives were selectively bound to the resin and the DMF water layer consisting of the inorganic salts in soluble form passed out as a flow-through fraction. The resin was then washed with 2 bed volumes of water at pH 7.0 and then 6-acetyl TGS fractions were eluted out and collected separately carefully
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using 35% methanol in water. Methanol from the pure 6-acetyl TGS fractions was removed by Falling Film evaporator.
The eluent fraction was then subjected to falling film evaporation to remove the methanol completely. The concentrate was then subjected to Ozonization by bubbling ozone gas through the solution. The volume of the solution was 1400 L containing 26.6 kg of 6-acetyl TGS. The initial colour index of the feed was 12500 CU on the Platinum Cobalt scale and the pH of the solution was 5.38. In the preferred process, the Ozone gas used for bubbling into the feed was generated as a gas containing high concentration of Ozone by using plant of Megazone series Model M212 (M/s. Aurozon P.O. Box 43, Pondicherry, India) Any other Ozone plant giving a gas containing Ozone at a concentration sufficient to cause decolorization can be used for the purpose of this invention. The bubbling rate was fixed to 150g/ hr of Ozone gas with a concentration rating of 7% nominal and maximal up to 14% w/w in Oxygen, although other rates of bubbling may also be used.
The pH of the solution was adjusted between 5-6 using 10% sodium hydroxide solution during the Ozonization. The Ozonization was completed after 14 hrs and the colour index of the solution after Ozonization was found to be 65 CU on the Platinum Cobalt scale. The 6-acetyl TGS before and after Ozonization remained the same without any loss.
This solution was then subjected to deacylation by addition of 35% sodium hydroxide solution to raise the pH up to 9.5 and monitored by TLC under stirring. After deacylation, the solution was subjected to extraction using ethyl acetate and concentrated.
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The TGS was then crystallized in a mixture of methanol and ethyl acetate and dried. The purity of the TGS isolated was found to be 99.6% with an overall yield Of 34.5%.

Dated this 8th day of January, 2007.

(MANISF SAURASTRI) KRISHNA & SAURASTRI
FOR PHARMED MEDICARE PVT. LTD. Jy their Agent
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