Aiming to develop innovative medical foods
“Development of a new concentrated liquid diet product found nowhere else”
How can we prevent complications such as aspiration pneumonia caused by liquid diets refluxing from the stomach, and diarrhea? We want to address such medical challenges and solve them with unprecedented, groundbreaking new products. Born from that challenge is a concentrated liquid diet product that is in liquid form when consumed but turns into a gel in the stomach.
Researchers from the Medical Foods Research Institute who were involved in development will tell the whole story—from the original idea, through the many trials and challenges, to the foundation that nurtured them.
Our manufacturing insights came from the medical field
Kazuya Mizugai Senior Researcher, MF Product Design Laboratory, Medical Foods Research Institute
Our newly developed concentrated liquid diet product uses pectin as a dietary fiber. It is normally a liquid, but when pH drops, its flow characteristics change from a liquid to a gel. Simply put, it changes from a liquid to a solid in the stomach when it is mixed with gastric acid. Why is something like this needed? If it remains a liquid, it may reflux from the stomach or move quickly from the stomach to the intestines and cause loose stools. We believe that those risks are reduced because it is easy to drink as a liquid that turns into a gel in the stomach.
For this reason, in the early 2000s, medical institutions took measures such as mixing pectin or agar into concentrated liquid diet products to pre-solidify them. Subsequently, various companies launched a range of semi-solid concentrated liquid diets. In 2007, we released the only semi-solid product on the market set with agar, and it earned positive evaluations from medical institutions. At the same time, we learned that users were calling for improvements to semi-solid concentrated liquid diets that are designed with high viscosity to achieve effects, because they were too firm and difficult to use.
While we were struggling with whether we could create something that can be used as a liquid and naturally solidifies in the stomach, an event occurred that became a decisive hint to a solution. We received a complaint that even when pectin was mixed into our concentrated liquid diet product, it did not solidify. When we tried it, sure enough, even after mixing pectin, it remained a free-flowing liquid. However, when we put it into artificial gastric juice, it solidified into a jelly-like state. At that moment, we were convinced that a groundbreaking new product unlike anything seen before could be created.
Pectin is a type of dietary fiber with many types available. It is commonly used in jams and similar products, gels in response to certain pH*1 and calcium levels, and is susceptible to heat. We reasoned that if we could find a pectin that can withstand sterilization (heat) during manufacturing, the path to formulation would open, so we searched materials and found a particular pectin. We also came to understand why a concentrated liquid diet that does not solidify even when pectin is mixed will gel upon contact with artificial gastric juice.
Around that time, we launched a project with staff from the Nutrition Laboratory and the Formulation Laboratory to develop next-generation products and began working on a new concentrated liquid diet based on this idea, handing off formulation research to Naoyuki Endo, a colleague in the MF Product Design Laboratory with extensive experience in formulation. In truth, what followed turned into a long, arduous journey, but thanks to the dogged efforts of the Formulation Laboratory team led by Mr. Endo, we were able to bring an innovative product to the world.
- pH: Hydrogen ion concentration index (a measure used to determine acidity or alkalinity)
We did not give up until we perfected the idea
Naoyuki Endo Senior Researcher, MF Product Design Laboratory, Medical Foods Research Institute
Once I took over formulation studies for the new product, the next steps were clear. A concentrated liquid diet product is a liquid preparation that contains protein, carbohydrates, fats, vitamins, and minerals. I understood based on data provided by Mr. Mizugai and from past experience that adding pectin causes proteins to aggregate and precipitate and makes separation of fats more pronounced. Since a concentrated liquid diet product must generally keep its nutritional components uniform, I believed that we could formulate it if we found a solution.
So first we tried, one after another, ingredients commonly used in concentrated liquid diets that we thought might contribute to quality stability. When sufficient results were not obtained, we expanded the scope and repeatedly conducted exhaustive screening of food materials and additives, and finally found something that could successfully homogenize the components.
We thought we were about 80% of the way to success, but unfortunately the prototype gelled after a few days even without any intervention. The cause was that the mechanism designed to gel upon mixing with gastric acid was prematurely activated during storage. We knew what kind of materials to add for improvement, but we had to avoid disrupting the nutritional balance as a concentrated liquid diet.
We couldn’t give up here. After that, endless days of grueling trial and error followed. With improvements, the period during which it remained stable without gelling gradually extended from a few days to a few weeks, and then to several months. From the time we took over the baton of formulation development, it ultimately took years before we could see a path to achieving the target shelf life of nine months. I am grateful to the company for allowing such a long-term challenge.
Working to discover new functionalities
Kazuo Hino Senior Researcher, MF Nutrition Research Laboratory, Medical Foods Research Institute
The MF Nutrition Research Laboratory to which I belong examines the physiological effects of products and verifies them through experiments. As formulation staff members Mr. Mizugai and Mr. Endo verified, we knew that this product solidifies in a beaker containing artificial gastric juice. Therefore, we first confirmed that the administered product actually gels in the stomach of animals. Next, we had to verify what physiological effects result from the product gelling in the stomach. We wanted to determine whether this product could reduce the risks of complications associated with liquid administration, such as reflux from the stomach and diarrhea. As a result of nonclinical experiments, we confirmed that the new concentrated liquid diet product is less prone to cause reflux and less likely to cause loose stools compared with general products.
Following these steps, we accumulated data on the anticipated product and confirmed that there were no issues with safety or nutritional effects when administered long-term. For drugs, clinical studies are conducted before marketing to confirm effects in patients, but no such studies are conducted for food. The data we provide is important information that serves as explanatory material to enable actual use of the product in medical settings.
Therefore, our efforts continue even after product launch. For example, the physiological effects of the dietary fiber and collagen hydrolysate contained in this concentrated liquid diet product is a very interesting topic. We collect feedback and data from patients and health care professionals, freely discuss ideas and questions across divisions and hierarchies, and identify new functionalities that the product may have. Enhancing product value through such challenges is also an important part of our work.
(Affiliated departments and job titles current as of the time of the interview.)
