WO2021167562A1

WO2021167562A1 - Nutritional compositions for cancer patients undergoing chemotherapy and/or radiotherapy and/or pre-post surgery

Info

Publication number: WO2021167562A1
Application number: PCT/TR2021/050062
Authority: WO
Inventors: Zafer Toksoz
Original assignee: Montero Gida Sanayi Ve Ticaret Anonim Sirketi
Priority date: 2020-02-21
Filing date: 2021-01-26
Publication date: 2021-08-26
Also published as: TR202002698A2

Abstract

The present invention relates to liquid compositions, comprising protein,carbohydrate, fat, fiber, vitamins, minerals combined with at least source of nucleobase, which provide nutritional support for cancer patients undergoing chemotherapy and/or radiotherapy and/or pre-post surgery.

Description

NUTRITIONAL COMPOSITIONS FOR CANCER PATIENTS UNDERGOING CHEMOTHERAPY AND/OR RADIOTHERAPY AND/OR PRE-POST SURGERY

Field of Invention

The present invention relates to liquid compositions providing nutritional support for cancer patients undergoing chemotherapy and/or radiotherapy and/or pre-post surgery.

The background of the invention

Cancer is currently a leading cause of deaths worldwide and the number of new cases is growing rapidly in both, developed and developing countries. Cancer is the second main cause of death worldwide. According to the World Health Organization (WHO), there were 18.1 million people new cases of cancer worldwide in 2018 and 9.6 million people died of the disease. Even so, early detection and advancements in medical treatment have greatly increased the number of cancer survivors. However, many cancer patients experience malnutrition and significant weight loss due to decreased food intake, emotional stress, and tumor-associated metabolic alterations. The nutritional status of cancer patients is a critical determinant of successful treatment and quality of life (QOL). Cancer therapy induced adverse events also contribute to malnutrition and delays in cancer therapies and may contribute to cancer deaths in a large proportion of patients.

For many patients, the effects of cancer and cancer treatments make it hard to eat well. Cancer treatments that affect nutrition include stem cell transplant, chemotherapy, hormone therapy, radiation therapy, surgery, immunotherapy. Specifically, when the head, neck, esophagus, stomach, intestines, pancreas, or liver are affected by cancer treatment, it is hard to take in enough nutrients to stay healthy.

Nutrition is a process in which food is taken in and used by the body for growth, to keep the body healthy, and to replace tissue. Good nutrition is important for good health. Eating the right kinds of foods before, during, and after cancer treatment can help the patient feel better and stay stronger.

Also, cancer and cancer treatments may affect the taste, smell, appetite, and the ability to eat enough food or absorb the nutrients from food. This can lead to malnutrition, which is a condition caused by a lack of key nutrients. Malnutrition can cause the patient to be weak, tired, and unable to fight infection or complete cancer treatment. Malnutrition can get worse if cancer grows or spreads. Taking the right amount of protein and daily caloric need is important for healing, fighting infection, and having enough energy.

The body needs protein for growth, repair body tissue, and to keep our immune systems healthy. Especially, people with cancer often need more protein than usual. After surgery, chemotherapy, or radiation therapy, extra protein is usually needed to heal tissues and help fight infection. When the body doesn’t get enough protein, it might break down muscle for the fuel it needs. This makes it take longer to recover from illness and can lower resistance to infection.

On the other hand, there are many types of high protein liquids or semi-liquid nutritional compositions currently on the market. The nutritional compositions provide to get the nutrients body needs. These nutrients include proteins, fats, carbohydrates, water, vitamins, and minerals. However, in the state of art, there is no nutritional composition particularly containing RNA in addition to these components for cancer patients to catalyze biochemical reactions, respond to cellular signals, regulate gene expression, synthesize proteins and to help cells grow rapidly.

In the patent literature also, there are nutritional compositions which are specifically formulated for different age ranges and for different objectives. They can be supplementary to malnourishment or they can provide complete nutrition.

For example, patent document numbered EP0756827B1 discloses the nutritional composition containing proteins and/or protein hydrolysates, carbohydrates, lipids, bulkages, and water particularly for patients with impaired immune function or patients with tumor.

The state of art includes about nutritional composition comprising protein, fat, carbohydrate, water, vitamin, mineral and ribonucleic acid. However, these compositions are not sufficient to meet the compositions required by cancer patients at the required rates.

Considering the state of art, there is still a need for nutritional compositions, customized for cancer patients undergoing chemotherapy and/or radiotherapy and/or pre-post surgery, providing complete and balanced nutrition helping to keep the body healthy, recover damaged tissue, catalyze biochemical reactions, synthesize proteins, assist in the rapid proliferation of cells while enhancing stability by reducing sedimentation and oxidation at the same time. During illness, treatment or recovery, daily need for calories and protein may be greater than usual.

In view of the present disclosure or through practice of the present invention, other advantages or the solutions to other problems may become apparent.

Objects and Brief Description of the Invention

Another object of the present invention is to obtain nutritional compositions enhancing stability by reducing sedimentation and oxidation at the same time.

Another object of the present invention is to obtain nutritional compositions having reduced osmolarity and osmolality, and accordingly enhanced patient compliance.

Another object of the present invention is to obtain nutritional compositions having balanced carbohydrate content which is free of glucose, ensuring patient’s daily energy need.

Another object of the present invention is to obtain nutritional compositions biocompatible components with no redundancy or competitive absorption.

Another object of the present invention is to obtain nutritional compositions essentially comprising water, at least one source of protein, at least one source of carbohydrate, at least one source of fat, at least one source of fiber, vitamins and minerals.

Another object of the present invention is to obtain nutritional compositions comprising a source of nucleobase to catalyze biochemical reactions, respond to cellular signals, regulate gene expression, synthesize proteins and assist in the rapid proliferation of cells.

Another object of the present invention is to obtain nutritional compositions comprising source of nucleobase in combination with vitamin D to support both immune, brain and nervous system health, healthy bones.

Another object of the present invention is to obtain nutritional compositions free of lactose to protect gastrointestinal system in cancer patients with sensitive stomach and gut. Another object of the present invention is to obtain nutritional compositions with enhanced fiber range to support gastrointestinal system.

Another object of the present invention is to obtain nutritional compositions comprising caseinates in specific ranges as protein sources to provide reduced osmolarity and sedimentation.

Another object of the present invention is to obtain nutritional compositions comprising docosahexaenoic acid and eicosapentaenoic acid in encapsulated form to reduce oxidation and provide deodorization.

Another object of the present invention is to develop a process for preparing such compositions to enhance homogenization and reduce oxidation.

Detailed description of the invention

In accordance with the objects outlined above, detailed features of the present invention are given herein.

The present invention relates to a liquid composition providing nutritional support for cancer patients undergoing chemotherapy and/or radiotherapy and/or pre-post surgery, comprising;

- water

- at least one source of protein is selected from the group comprising sodium caseinate and calcium caseinate or mixtures thereof,

- at least one source of carbohydrate,

- at least one source of fat,

- at least one source of fiber,

- vitamins,

- minerals, wherein the composition further comprises at least one source of nucleobase in combination with vitamin D; and the weight ratio of said source of nucleobase to vitamin D is in the range of 1:0.00007 to 1 :0.0007, preferably 1 :0.00003 to 1 :0.0003.

In an embodiment, said source of nucleobase is selected from the group comprising subunits of ribonucleic acid ("RNA"), polymeric forms RNA, yeast RNA, or combinations thereof.

According to the preferred embodiment, said source of nucleobase is RNA (ribonucleic acid). RNA (ribonucleic acid) is a chemical compound that can be made by the body. RNA (ribonucleic acid) can also be made in a laboratory. RNA is used as medicine or health supplements.

RNA also performs many functions in multi-cell organisms such as catalyzing biochemical reactions, responding to cellular signals, regulating gene expression, synthesizing proteins and assisting in the rapid proliferation of cells. Also, RNA in the early postoperative time period improves postoperative immunologic responses and helps to overcome more rapidly the immunologic depression after surgical trauma, treatment of chemotherapy, treatment of radiotherapy. Multi-cell organisms also synthesize proteins with RNA.

The primary value of RNA as a health supplement deals with its ability to assist in the rapid proliferation of cells. This property is especially useful during surgery, chemotherapy, radiotherapy, injury and attacks on the immune system. For these reasons, RNA supplementation has a critical importance for cancer patients undergoing chemotherapy and/or radiotherapy and/or pre-post surgery.

In the most preferred embodiment, the composition comprises RNA as source of nucleobase in an amount of 0.05 - 0.5 g/100ml_.

According the most preferred embodiment, the nutritional composition comprises at least one source of nucleobase and vitamin D in combination.

On the other hand, RNA improves memory and mental sharpness, treats depression, increases energy. Also, RNA helps preserve bone mass and strength. And in those who have had cancer, it speeds and aids recovery.

Similarly as RNA, Vitamin D has multiple roles in the body. Vitamin D assists in promoting healthy bones, treating depression, supporting immune, brain, and nervous system health and influencing the expression of genes involved in cancer development. Also, Vitamin D plays a significant role in the regulation of calcium and maintenance of phosphorus levels in the blood. These factors are vital for maintaining healthy bones. Vitamin D deficiency manifests as a softening of the bones in cancer patients vitamin D deficiency results in poor bone density and muscular weakness.

Also, vitamin D deficiency may play a role in depression and possibly other mental disorders. Research indicates that vitamin D may improve many health outcomes, particularly cancer. In the light of these information, ribonucleic acid is combined specifically with vitamin D to provide an enhanced effect on support immune, brain and nervous system health, healthy bones. It has been observed that this combination increases the absorption of these components through the patient’s digestive system. Accordingly, increase in the effectiveness of the components is also expected.

The weight ratio of source of nucleobase to vitamin D is in the range of 1 :0,000007 to 1 :0.00007, preferably 1:0.00003 to 1 :0,0003. It has been surprisingly seen that absorption of these two components can be increased even more by using specifically these ranges.

According to one embodiment, said source of carbohydrate is selected from the group comprising sucrose, maltodextrin, fructose, hydrolyzed corn starch, corn syrup solids, high fructose corn syrup or mixtures thereof.

Preferably, the composition is free of glucose to reduce insulin resistance, especially in cancer patients who have prediabetes and who are likely to develop type 2 diabetes. Prediabetes usually occurs in people who already have some insulin resistance or whose beta cells in the pancreas aren’t making enough insulin to keep blood glucose in the normal range. Glucose intake significantly increases this risk since it is absorbed directly across the lining of the small intestine into your bloodstream, which delivers it to your cells and it raises blood sugar more quickly than other sugars, which stimulates the release of insulin.

Additionally, in a preferred embodiment, the composition is also free of lactose to increase patient compliance; since studies demonstrate that the prevalence of lactose malabsorption increases significantly patients with cancer.

In the preferred embodiment; the composition comprises maltodextrin and sucrose. The weight ratio of maltodextrin to sucrose is in the range of 1:0.1 to 1:1, preferably 1:0.25 to 1:0.45. It has been surprisingly seen that the osmolality of the composition can be reduced by using specifically these ranges.

Accordingly, the osmolality of the composition is in the range of 100-1000 mOsm/kg water, preferably 200-800 mOsm/kg water. Besides, the osmolarity of the composition is in the range of 100-800 mOsm/L, preferably 200-600 mOsm/L. According to one embodiment, said source of protein is selected from the group comprising casein, soy, rice, pea, carob, oat, whey, caseino-glyco-macropeptides or mixtures thereof.

Preferably, the composition is free of whey to provide a balanced solid content and to achieve good heat stability and flowability on tubular plant production.

According to the preferred embodiment, the composition comprises sodium caseinate and calcium caseinate as protein sources. The weight ratio of sodium caseinate to calcium caseinate is in the range of 1 :0.1 to 1 :10, preferably 1 :2 to 1:5. Specifically, these ratios provide enhanced stability by reducing sedimentation over time and increase shelf-life accordingly. It has been also observed that the use of sodium caseinate and calcium caseinate as protein sources supports the reduction of osmolality. Most preferably, said ratio is 1 :4.

According to one embodiment, said source of fat is selected from the group comprising fish oil, medium-chain triglycerides, rapeseed oil, sunflower oil, high oleic sunflower oil, safflower oil, rapeseed oil, soy oil, olive oil, canola oil, corn oil, peanut oil, rice bran oil, butter fat, hazelnut oil, structured lipids or mixtures thereof.

According to the preferred embodiment, said source of fat is selected from the fish oil, medium- chain triglycerides, rapeseed oil, sunflower oil, high oleic sunflower oil or mixtures thereof. This selection of fat source has been shown to reduce oxidation and prolong the shelf life of the composition.

According the preferred embodiment, the composition further comprises docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). Most preferably, DHA and EPA are included in the composition in the encapsulated form to assure the deodorization of the fishy flavor and odor. Additionally, encapsulation reduces oxidation during the production process and the shelf-life.

Specific ranges of a combination of DHA and EPA, which have been surprisingly found during the trials, are used to reinforce the reduction of oxidation. According to one embodiment, the weight ratio of total fat to a combination of docosahexaenoic acid and eicosapentaenoic acid is in the range of 1 :0.05 to 1 :0.2, preferably 1:0.1 to 1 :0.2.

According to the one embodiment, said source of fiber is selected from the group comprising fructooligosaccharides, inulin, guar gum, xanthan gum, xylooligosaccharides, gum arabic, pectin, acacia gum, resistant starch, dextrans or mixtures thereof. According to the preferred embodiment, the composition comprises fructooligosaccharides and inulin. Preferably, the total amount of fructooligosaccharides and inulin is 1-4 g/100ml_, most preferably 1.75-2.25 g/100ml_. It is aimed to improve the bowel functions of cancer patients by the specific selection of these water-soluble fibers and their amounts which are relatively high considering the prior art.

According the one embodiment, the nutritional composition includes vitamins selected from the group comprising of vitamin A, Vitamin B1 (thiamine), VitaminB2 (riboflavin), Vitamin B3 (niacin or niacinamide ), Vitamin BS (pantothenic acid), Vitamin B6 (pyridoxine, pyridoxal, or pyridoxamine, or pyridoxine hydrochloride), Vitamin B7 (biotin), Vitamin B9 (folic acid), and Vitamin B12 (various cobalamins; commonly cyanocobalamin in vitamin supplements), vitamin C, vitamin D, vitamin E, vitamin K, K1 and K2 (i.e. , MK-4, MK-7), folic acid, biotin, choline or combinations thereof.

According to the one embodiment, the nutritional composition comprises minerals selected from the group comprising of sodium, potassium, phosphorus, magnesium, chloride, iron, zinc, manganese, fluoride, copper, iodine, selenium, chromium, boron, molybdenum, nickel, tin, vanadium, zinc, or combinations thereof.

According to the one embodiment, the nutritional composition can be administered orally or via tube feding.

According to the one embodiment, the energy value of the composition is in the range of 140- 170 kcal/100 mL to ensure the daily energy needs of cancer patients.

According to one embodiment, the composition comprises;

- 8-12 g/100ml_ protein

- 10-20 g/100ml_ carbohydrate

- 3-6 g/100ml_ fat

- 300-1200 mg/100ml_ docosahexaenoic acid and eicosapentaenoic acid in total

- 1-3 g/100m L fiber

- 100-300 mg/100ml_ ribonucleic asid

According to one preferred embodiment, the composition further comprises;

- 40-100 mg/100ml_ choline - 50-150 mcg/100ml_ palmitat

- 50-100 mcg/100mL beta-carotene

- 3-90 mcg/100ml_ vitamin D

- 1-6 mcg/100ml_ vitamin E

- 10-30 mcg/100ml_ vitamin K

- 20-40 mg/100ml_ vitamin C

- 40-100 mcg/100ml_ folic acid

- 0.1-0.5 mg/100ml_ vitamin B1

- 0.1-0.5 mg/100mL vitamin B2

- 0.1-0.5 mg/100ml_ vitamin B6

- 0.3-1 mcg/100m L vitamin B12

- 2-5 mg/100ml_ vitamin B3

- 0.5-5 mg/100ml_ vitamin B5

- 3-10 mcg/100ml_ vitamin B7

- 50-300 mg/100ml_ sodium

- 100-400 mg/100ml_ potassium

- 40-100 mg/100m L chloride

- 100-500 mg/100ml_ calcium

- 50-200 mg/100m L phosphorus

- 10-50 mg/100ml_ magnesium

- 1-5 mg/100ml_ iron

- 1-5 mg/100ml_ zinc

- 0.1-1 mg/100ml_ manganese

- 100-500 mcg/1 OOmL copper

- 10-50 mcg/1 OOmL iodine

- 5-20 mcg/100mL selenium

- 5-20 mcg/100mL chromium

- 10-30 mcg/1 OOmL molybdenum

These analytically selected ratios ensure the required effective doses for complete nutrition, toxic safety and patient compliance. Furthermore, they enhance the stability and prolonged shelf-life.

According to all these embodiments, the below-given formulations can be used in the liquid composition subjected to the invention. Example 1 : Liquid composition providing nutritional support for cancer patients undergoing chemotherapy and/or radiotherapy and/or pre-post surgery

Example 2: Liquid composition providing nutritional support for cancer patients undergoing chemotherapy and/or radiotherapy and/or pre-post surgery

The preparation method of the above-mentioned liquid compositions given in examples 1 and 2 is prepared by following these steps: a. Blending water-soluble components in water b. Pasteurizing the mixture c. Adding fat sources to the mixture d. UHT processing the total mixture

Claims

1. A liquid composition providing nutritional support for cancer patients undergoing chemotherapy and/or radiotherapy and/or pre-post surgery, comprising;

- water

- at least one source of protein,

- at least one source of carbohydrate,

- at least one source of fat,

- at least one source of fiber,

- vitamins,

- minerals, wherein the composition further comprises at least one source of nucleobase in combination with vitamin D; and the weight ratio of said source of nucleobase to vitamin D is in the range of 1:0.00007 to 1:0.0007, preferably 1:0.00003 to 1:0.0003.

2. The composition according to claim 1, wherein said source of nucleobase is selected from the group comprising subunits of ribonucleic acid ("RNA"), polymeric forms of RNA, yeast RNA, and mixtures thereof.

3. The composition according to claim 1, wherein said vitamins are selected from the group comprising vitamin A (palmitate), beta carotene, vitamin E, vitamin K, vitamin C, folic acid, vitamin B1 (thiamine), vitamin B2 (riboflavin), vitamin B3 (niacin), vitamin B5 (Pantothenic acid) vitamin B6 (pyridoxine), vitamin B7, Vitamin B9 (folic acid), vitamin B12, choline or combinations thereof.

4. The composition according to claim 1 , wherein said source of carbohydrate is selected from the group comprising sucrose, maltodextrin, fructose, hydrolyzed corn starch, corn syrup solids, high fructose corn syrup or mixtures thereof.

5. The composition according to claim 4, wherein the composition comprises maltodextrin and sucrose.

6. The composition according to claim 5, wherein the weight ratio of maltodextrin to sucrose is in the range of 1 :0.1 to 1 : 1 , preferably 1 :0.25 to 1 :0.45.

7. The composition according to claim 1, wherein said source of protein is selected from the group comprising casein, soy, rice, pea, carob, oat, whey, caseino-glyco- macropeptides or mixtures thereof.

8. The composition according to claim 7, wherein the composition comprises sodium caseinate and calcium caseinate.

9. The composition according to claim 8, wherein the weight ratio of sodium caseinate to calcium caseinate is in the range of 1:0.1 to 1:10, preferably 1:2 to 1:5, more preferably it is 1:4.

10. The composition according to claim 1, wherein said source of fat is selected from the group comprising fish oil, medium-chain triglycerides, rapeseed oil, sunflower oil, high oleic sunflower oil, safflower oil, rapeseed oil, soy oil, olive oil, canola oil, corn oil, peanut oil, rice bran oil, butter fat, hazelnut oil, structured lipids or mixtures thereof.

11. The composition according to claim 10, wherein said source of fat is selected from the fish oil, medium chain triglycerides, rapeseed oil, sunflower oil, high oleic sunflower oil or mixtures thereof.

12. The composition according to claim 1, wherein the composition further comprises docosahexaenoic acid and eicosapentaenoic acid.

13. The composition according to claim 12, wherein said docosahexaenoic acid and eicosapentaenoic acid are present in the encapsulated form in the composition.

14. The composition according to claim 12 or 13, wherein the weight ratio of total fat to docosahexaenoic acid and eicosapentaenoic acid is in the range of 1:0.05 to 1:0.2, preferably 1:0.1 to 1:0.2.

15. The composition according to claim 1, wherein said source of fiber is selected from the group comprising fructooligosaccharides, inulin, guar gum, xanthan gum, xylo- oligosaccharides, gum arabic, pectin, acacia gum, resistant starch, dextrans or mixtures thereof.

16. The composition according to claim 15, wherein the composition comprises fructooligosaccharides and inulin in a total amount of 1-4 g/100ml_, preferably 1.75- 2.25 g/100ml_.

17. The composition according to claim 1 , wherein said minerals are selected from the group comprising sodium, potassium, chloride, calcium, phosphorus, magnesium, iron, zinc, manganese, copper, iodine, selenium, chromium, molybdenum or mixtures thereof.

18. The composition according to any one of the preceding claims, wherein the composition comprises

- 8-12 g/100ml_ protein

- 10-20 g/100ml_ carbohydrate

- 3-6 g/100ml_ fat

- 300-1200 mg/100ml_ docosahexaenoic acid and eicosapentaenoic acid in total

- 1-3 g/100m L fiber

- 2-5 mcg/100ml_ vitamin D

- 100-300 mg/100 ml_ ribonucleic acide

19. The composition according to claim 18, wherein the composition further comprises

- 40-100 mg/100ml_ choline

- 50-100 mcg/100ml_ palmitate

- 50-100 mcg/100ml_ beta-carotene

- 1-6 mcg/100ml_ vitamin E

- 10-30 mcg/100ml_ vitamin K

- 20-40 mg/100ml_ vitamin C

- 40-100 mcg/100ml_ folic acid

- 0.1-0.5 mg/100ml_ vitamin B1

- 0.1-0.5 mg/100ml_ vitamin B2

- 0.1-0.5 mg/100ml_ vitamin B6

- 0.3-1 mcg/100m L vitamin B12

- 2-5 mg/100ml_ vitamin B3

- 0.5-5 mg/100ml_ vitamin B5

- 3-10 mcg/100ml_ vitamin B7

- 50-300 mg/100ml_ sodium

- 100-400 mg/100ml_ potassium

- 40-100 mg/100m L chloride - 100-500 mg/100ml_ calcium

- 50-200 mg/100 L phosphorus

- 10-50 mg/100ml_ magnesium

- 1-5 mg/100ml_ iron

- 1-5 mg/100ml_ zinc

- 0.1-1 mg/100ml_ manganese

- 100-500 mcg/100ml_ copper

- 10-50 mcg/100ml_ iodine

- 5-20 mcg/100ml_ selenium

- 5-20 mcg/100ml_ chromium

- 10-30 mcg/100ml_ molybdenum

20. The composition according to any one of the preceding claims, wherein the energy value of the composition is in the range of 140-170 kcal/100 ml_.

21. The composition according to any one of the preceding claims, wherein the composition is free of lactose and arginine.

22. A process for preparing the composition according to any one of the preceding claims, comprising the following steps:

- Blending water soluble components in water

- Pasteurizing the mixture

- Adding fat sources to the mixture

- UHT processing the total mixture