The true about Neohesperidin Dihydrochalcone.

In 1975 started Mr. Tomás Serrano Alvarez, owner of Laboratory Oftalmia, at Beniaján (Murcia) with the production of Hesperidin. This was possible thanks to a good research understanding with the university of Murcia, viz.: Prof. Dr. Francisco Sabater and Prof. Dr. Miguel Sánchez. In a very short time Oftalmiso was a good competitor of the multinational Merck of Darmstadt.

In 1976, Mr. Tomás Serrano Alvarez decided to construct an industrial complex of about 50.000 square meters because of the excellent sales and good future possibilities of Hesperidin. Having started to work in 1974 in laboratory Oftalmismo in the export department I had an excellent business collaborationship that time with my director, the export manager Mr. Juan Salar, who was also interested in the production of the sweetener Neohesperidin Dihydrochalcone. When I decided to travel to my country (Holland) to see the export possibilities for Hesperidin and Citrus Bioflavonoids, he asked me to find out on the university of Amsterdam more information about the bioflavonoid "Neohesperidin", raw material for the production of the sweetener Neohesperidin Dihydrochalcone. because during his visit in France he was documentally informed of this sweetener that presumingly was produced by Jafora in Israel in collaborationship with the Weizmann Institute.

After having visited possible interesting firms for Hesperidin and Citrus Bioflavonoids I realized that for this type of products there still was not a ready market in Holland and so before flying back to Spain I decided to visit the university of Amsterdam, where after one day of intense reading I was able to obtain an very old paper of the year 1949 written in German that spoke in details how to obtain Neohesperidin. When being back in Spain I informed Mr. Salar of the content of this research paper and maybe as a result of that the the following notice was published in IMS Pharmaceutical Marketletter, Vol. 4, No 27, July 4, 1977:

OFTALMISMO SWEETENER PROJECT

A small and independent Spanish pharmaceuticals firm, Oftalmiso SA, has disclosed plans for an ambitious three-stage expansion of bioflavonoids production, with an eye on the artificial sweetener market. The Murcia-base firm, which already supplies about 25% of total world demand for Hesperidin (Vitamin P) and 15% of all citroflavooids (Vitamin P complex), will initially double hesperidin output capacity to 200 tons per year and raise citroflavonoid production from 80 to 150 tons per year. Oftalmiso is investing 98 million pesetas ($1.4 millon) in this stage of its expanded production programme.

The company has developed its own technology for manufacture of the citrus-based sweetener neohesperidin dihydrochalcone, for which international patents rights are pending. Research in the U.S., Israel and the Soviet Union reportedly are also working with bioflavonoids as a possible replacement for saccharin and cyclamates in the artificial sweetener market. No health risks have been discovered in the substance to date, which is said to be 1,500 times sweetener than sugar by weight. In addition, bioflavonoids have a wide range of therapeutic applications, particularly as capillary protecters, and are used increasingly in the preservation of natural flavourings and foodstuffs. Oftalmiso is continuing its search for pharmaceutical applications of local raw materials, particularly citrus fruits.

That time Oftalmiso did not have any own technology for the manufacturing of this sweetner and appearantly this message was given to IMS for especial commercial reasons. Maybe to obtain more credits from the banks? Due to the fact that credits had to be paid very soon and the construction of the new plant could not be effected in time, Oftalmiso became in financial problems and was declared months later in suspension of payments.

The result of that was that Prof. Dr. Miguel López founded thereafter with his brother, José López Sánchez - that time General Manager of an important preserve industry in the north of Spain - and other members of the family, business friends, as well as important professors of the university and myself, the firm Zoster S.A.
My previous director, Mr. Salar continued in Oftalmiso and started lateron working for some years with another company called Extracciones del Sureste that took over Oftalmiso to continue the production of Hesperidin.
Thereafter he worked for at least ten years in Nigeria. When creating Zoster S.A., Prof. López informed me that my future job would be taking charge of the export of the Hesperidin and Citrus Bioflavonoids, as well as the research of new products that could be produced in Zoster S.A.

Due to my previous job and having in my posession the german paper how to extract Neohesperidin, I tried to promote the production of this sweetener in Zoster. Unfortunately the Chief Chemist that time in charge of the production of Hesperidin and Bioflavonoids was not able to extract the product. According to his saying he had done the trials, but the results were bad and consequently the idea of this sweetener was abandoned. However, I did not give up this project, in which I seriously believed and wanted to have this product produced in Zoster, sothat I during years tried to convince the other shareholdes of this opportunity. I had in this sense lateron the help of the general manager, Mr. José López Sánchez, who arranged the necessary cientific contacts. Another chemist in Zoster succeeded in extracting the neohesperidin and the project was given to Prof. Dr. Francisco García Sabater, who succeeded in collaborationship with Prof. José Antonio del Ríos of the university of Murcia to produce on pilote scale the so desired Neohesperidin Dihydrochalcone. Thereafter things were moving quickly in Zoster, because in a rather short time an industrial plant was created in 1982 for the daily production of this sweetener. In that time the sweetener was only allowed in Belgium and after several investigations a buyer was found for the same in the form of a flavour company that used the sweetener in their flavours. During a visit several months later in 1983 to the flavour company in Belgium, the owner declared that Jafora could not produce sufficient quantities and after having assuring that Zoster was able to produce the quantities needed, a contract with substantial quantities was obtained.

Due to the fact that Jafora was not able to supply sufficient toxicological papers, the Belgish flavour company pressed to arrange this, because otherwise there would be a great possibility that the sweetener would be prohibited in Belgium again. Therefore I visited several times the institute T.N.O in the Netherlands, where the necessary toxicological studies were undertaken with good success. The toxicological papers in question were given in time to the company in Belgium, but unfortunately the company informed us a year later that they had abandoned the sweetener in their flavours. Consequently it was my responsability to find another application for this sweetener, because this was the only customer using this in food. After the necessary research, trials and work I succeeded several months later to find a new application for this sweetener. And so I started to promote the sweetener in the animal feed industry with good results. This is now the main application for this sweetener in the world..

Beginning 1982 a new young chemist, Mr. Julián Castillo Sánchez, entered in Zoster and in 1985 another young chemist, Mr. Obdulio Benavente García. Both became shareholders in Zoster and lateron they were the first in developing another new interesting sugar, namely L-Rhamnose, from citrus bioflavonoids that I pretended to have produced in Zoster. It was again Prof. Sabater who had to interfere for having produced this sugar in Zoster. Apparently this team of Prof. Sabater and these two young chemists worked very well, because lateron Dr. Castillo and Dr. Benavente suceeded in higher yields of the sweetener Neohesperidin Dihydrochalcone during processing and it was Dr. Castillo that suceeded in producing this sweetener with better solublity in certain liquids. These two young chemists were in Zoster the drive for new products and new qualities of the same till the sale of Zoster in 1989. Thereafter the new owners had other ideas and the research of new products was abandoned. During at least 8 years all shareholdes of Zoster could not make any competition to the new owner and so being free in 1998 Dr. Castillo and Dr. Benavente thought it was time to leave their forced isolation and they started working in another company, where in a very short time they were able to create more than 20 new products. They learned well their lessons with Prof. Sabater and now the spirit of Prof. Sabater is seen each time when they create another new product. Today they belong to the best scientists in the world for citrus bioflavonoids.