Pharma & Healthcare News October 2015 by Alsiano A/S

Pharma & Healthcare News Alsiano No. 21 • October 2015

Contents Lynside Pro GI+ becomes ibSium .....................................1 Xylitol and erythritol for direct compression .................2 New KitoZyme study completed with promising results.......................................3 MICROCEL® Microcrystalline cellulose...................................4 Egg albumen protein is an effective protein source . .......5 OleoGrape®SEED - powerful antioxidant..............................6 The Alsiano Healthcare team ........................................8

Lynside Pro GI+ becomes ibSium The all-natural long-term solution from Lesaffre Human Care to reduce abdominal pain and discomfort is currently being rebranded as ibSium. Same innovative ingredient – now stronger identity Aiming at increasing visibility and raising awareness about Lesaffre Human Care’s probiotic yeast, Lynside Pro GI+ is being rebranded. ibSium benefits from a brand new identity: new logo, new graphics, etc. Therefore, you will be presented with an enhanced offer to fulfil all your needs: a unique product with a strong identity, backed by the scientific community, combined with a complete and customisable toolbox and comprehensive support. New identity – same innovative ingredient Although Lesaffre Human Care has chosen to strengthen the brand image of this innovative product through a new identity, the ingredient itself has not changed. Therefore, ibSium is still: • A unique and patented strain of Saccharomyces cerevisiae selected by Lesaffre among thousands of proprietary strains • and registered with the French National Collection of Microorganism Cultures as CNCM¬3856. • An innovative and natural ingredient which has demonstrated a significant effect relieving abdomi-

nal pain and discomfort of individuals with irritable bowel syndrome (IBS) through - 2 clinical studies on a total of 600 volunteers with IBS and conducted by independent experts in Gastroenterology - 1 consumer study implemented in collaboration with prescribing physicians on more than 1160 volunteers presenting symptoms of IBS In addition, ibSium has • An important backing from the scientific community with the publication of results of the first clinical study in the journal “Digestive and Liver Disease”, and recently, the findings of a new clinical study has been accepted for publication in United European Gastroenterology Journal. • Absence of adverse side effects or habituation, allowing consideration for long-term use. • Fast-acting solution with signs of improvement felt within the first few days of consumption. (continues on page 2 >>)

Health claim for ibSium in Canada

Publisher: Alsiano A/S Circulation: 550 copies

- read more on p.2.

Editor-in-chief: Anders Hager Coordinator, text, lay-out: Dorthe Andersson Pharma & Healthcare News is published twice a year and distributed to customers and other interested parties. Reproduction of articles appearing in Pharma & Healthcare News requires prior consent of the author. Alsiano is not responsible for the content of articles written by external authors.

Pharma & Healthcare News Food News

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Alsiano Alsiano

Xylitol and erythritol for direct compression Futaste erythritol and xylitol contribute effective compaction properties within specific tableting applications and usages Futaste Europe offers direct compression versions (DC) of erythritol and xylitol to the tableting industries for filling or binding applications. Both products are sugar free low calorie bulk sweeteners containing exceptional sweetness and providing flavour improvement.

Europe products can provide the desired texture, appearance and dosage combined with mouthfeel and sweetness flavour which are key components of various formulations.

DC production methodology requires excipients of a high quality and functionality. Xylitol and erythritol can contribute where simple tableting applications are required. They are now increasingly used and principally adapted to direct compression applications for high-quality chewable lozenges or tablets, with a pleasant taste and texture.

Xylitol, already well regarded for its excellent oral care and dental properties in the oral consumable confectionery market of chewing gums, can offer calorie reduction, sweetness, flavour enhancement and cooling effect as well. Erythritol also provides excellent sweetness and offers zero calorie opportunities and product claims.

Directly compressible xylitol and erythritol for simple tablet manufacturing • Pleasant taste • Smooth mouthfeel and texture • Low or almost zero calorie • Cooling effect • Tooth-friendly

Low and almost zero calorie Erythritol and xylitol can offer tableting processors potential to utilise a low kcal product and almost zero kcal too if erythritol is chosen. The Futaste

For further information please contact Alsiano.

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>> • EU QPS (Qualified Presumption

of Safety) microorganism and US GRAS (Generally Recognized as Safe) status. In a nutshell, ibSium is a natural alternative to prescription drugs often used in intestinal pain and discomfort management. ibSium can be considered as a safe and efficient innovative strategy for long term use in improving the quality of life of people suffering from digestive disorders by easing their symptoms.

More recognition to ibSium from the scientific community ibSium’s role in helping to reduce Irritable Bowel Syndrome symptoms has again raised the interest of the scientific community. The findings of a new clinical study have recently

Health claim for ibSium in Canada Based on the findings of the first clinical trial, which were recently published in the journal “Digestive and Liver Disease”, Health Canada has granted Lesaffre Human Care a new condition-specific claim for ibSium. The newly approved claim is as follows: “Helps reduce abdominal pain and discomfort associated with irritable bowel syndrome (IBS)”. Obtaining this new health claim is a big win for Lesaffre Human Care; rewarding both its commitment to providing innovative solutions to global health care challenges; and the company’s long term investment in providing strong scientific and clinical data to substantiate the benefits of its patented strain of Saccharomyces ce-revisiae in individuals. A finished product also called ibSium is expected to be launched in Canada in the coming months by Medical Futures Inc.

been accepted for publication in the renowned peer-reviewed “United European Gastroenterology Journal”. As reported in the article, ibSium demonstrated a significant effect in the improvement of gastrointestinal

symptoms in the subjects. With this new official publication, ibSium becomes the best substantiated natural ingredient with a clinically proven effect on IBS symptoms. Article 414

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New KitoZyme study completed with promising results A new clinical study involving around 100 persons has demonstrated excellent results achieved with KiOnutrime-CsG, which helps combat excess weight and obesity By KitoZyme KitoZyme operates in three segments of the healthcare sector: digestive health, weight management and cardiovascular health. The study related to a product within weight management has just been completed. More specifically, the objective was to verify and demonstrate the reduction in bodyweight in overweight and obese subjects as a result of the lipidabsorbing capacity of KiOnutrime, an innovative product developed by KitoZyme and derived from natural fibre of fungal origin. The conclusion and results of this clinical study are very promising since patients recorded a clear, progressive reduction in their weight. Around 100 patients were involved in the study which also demonstrated statistically significant reductions in body fats and abdominal, hip and waist measurements in people who took

KiOnutrime-CSG. The full results of the study are soon to be published in a renowned scientific journal.

“ Patients recorded a clear, progressive reduction in their weight”

The clinical trial requirements in detail The multicentre clinical trial took place in four hospitals and medical research centres between the end of 2014 and the start of 2015. A total of 96 people - men and women who were overweight (BMI of 26-35) and aged between 18 and 65 years were divided into two groups. The 64

The unique nature of KitoZyme’s chitosan KiOnutrime-CsG is a unique natural fibre extracted from fungi using a patented process developed by KitoZyme. It dissolves in 10 minutes in the acidic environment of the stomach. That means that a dose can be administered almost immediately before a meal which makes it convenient and easy for consumers to take. It is also suitable for vegetarians and is certified halal and kosher. KiOnutrime-CsG is authorised in the EU under the Novel Food Regulation and is also approved by EFSA to bear the health claim that it maintains a healthy level of cholesterol (lipid) in the blood. The active ingredient also holds GRAS status as awarded by the US FDA.

people in the treatment group were given five capsules per day, each containing 500 mg of KiOnutrime-CsG. The 32 people enrolled in the control group followed the same procedure but their capsules contained a placebo. All patients maintained their usual eating habits and did not change their lifestyle. Weight loss was on average 3.2 kg in the group receiving treatment. Article 415

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MICROCEL® Microcrystalline Cellulose MICROCEL® from Blanver is the preferred excipient for use in tablets, capsules, granules, pellets and spheres Microcrystalline Cellulose (MCC) is a partially depolymerised pure cellulose. Its appearance is a white, insoluble, odorless and tasteless powder, composed of highly compressible porous particles. Blanver’s MICROCEL line consists of various types distinguished by their particle size and are typically used in tablets, capsules and pellets. ®

As a compression or compaction aid, MICROCEL® promotes: • High hardness of tablets with low pressure in the tablet press • Low friability and minimal weight variation • Excellent die filling • Fast disintegration • Enhanced tablets with poor compressible APIs

MICROCEL® types for each manufactured process The MICROCEL® range consists of four different types. The range of recommended levels of use for all applications for the four types, either in wet granulation or in direct compression, is usually between 10 and 90%. Each type is able to function in the following manufacturing processes: MICROCEL® 101: Wet Granulation, API Adsorption/Absorption, Vegetable Extract Adsorption/Absorption and Pellet & Spheronisation;

MICROCEL® 102: Wet Granulation, Direct Compression, API Adsorption/ Absorption, Vegetable Extract Adsorption/Absorption, Capsule (Automatic Filling); MICROCEL® 12 & 200: Direct Compression, Poor Flowing APIs, API Adsorption/Absorption, Vegetable Extract Adsorption/Absorption, Capsule (Semi-Automatic Filling). Regulatory Information CAS: 9004-34-6 DMF (US FDA): 9201 (continues on page 5 >>)

Applications MICROCEL® is the preferred excipient for use in tablets, capsules, granules, pellets and spheres, as it enhances the adsorption and absorption of drugs for solid dosage formulations. It is able to function in the applications shown in the table below.

MICROCEL® applications

of n n n tio o sio s i ct t olu u g i a r & r t d u d s n t b x t ai n dr rm ad n tio ex ria an n se sio le es latio r for id fo sorp sf te gr utio t id es b t e a e r r a a c it e u e d p t ta er it u nt l en cil rri liq du cil an la nd om gen Flow Disi isso ge rri lu Fa Bi Re Fa gr Oi d Di Ca in C a Ve ca y ilit

Tablets for direct compression

MICROCEL®

Tablets by wet granulation

is the excipient preferred worldwide for use in tablets manufactured by direct compression.

Capsules (automatic machine) Capsules (semi-automatic machine Granules Pellets and spheres API adsorption API absorption

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Egg albumen protein is an effective protein source EAP-Sport from Pulviver offers an alternative protein source with high biological protein quality when lactose intolerance or cow milk allergy is an issue Athletes need protein primarily to repair and rebuild muscles broken down during exercise and to help optimise carbohydrate storage in the form of glycogen. Whey proteins and casein are common and well-known sources, but unfortunately not fitted for persons with lactose intolerance or cow milk allergy. Pulviver offers an alternative which is completely milk and lactose free – EAP-Sport, 100% egg albumen protein. Egg albumen protein is the best replacer for milk proteins and EAP-Sport is easy to dissolve due to a unique instant process.

Egg albumen, a natural source of proteins Egg albumen powder is the result of a simple and clean production process. After the separation of the egg yolk and the egg white, the liquid is spray dried and pasteurised. No chemical treatment whatsoever is applied. The result is a pure ingredient which still contains all the vitamins and minerals naturally present in the egg albumen.

Egg albumen contains interesting levels of amino acids. All 9 essential acids are present, and all 3 BCCA’s (Branched Chain Amino Acids) which are essential for intensive muscular activity are naturally present. As egg albumen is a protein source of animal origin, its amino acid composition is comparable with whey protein concentrate.

EAP-Sport - applications • Single source used as medium rate digesting protein • Used in a blend to create a steadier, sustained release of amino acids into the bloodstream. • Excellent alternative for whey and casein

(continues on page 6 >>)

• 100% egg albumen • > 84% protein content* • Similar high biological protein quality • Conservation of all naturally present minerals and vitamins • Easy to dissolve – no lumps • Neutral flavour and taste *calculated on dry matter content; Kjeldahl N x 6.25)

MICROCEL®

comparative characteristics Types

Differential analysis

101

102

200

Average particle size (microns)

100

160

180

Retained on 60 mesh (%)

NMT 1

NMT 8

NLT 10

Retained on 100 mesh (%)

NLT 40

NLT 50

Retained on 200 mesh (%)

NMT 30

NLT 45

Loss on drying (%)

NMT 7

Bulk density (g/cm3)

0.26-0.31

0.28-0.33

0.30-0.40

0.33-0.44

NMT = No More Than - NLT = No Less Than

BLANVER is a global leader with more than 30 years of experience in the production of excipients for the pharmaceutical, food and cosmetic industries. Blanver products comply with the highest quality standard and are present in various formulations in more than 100 countries worldwide. Article 416

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OleoGrape®SEED - powerful antioxidant A study shows that OleoGrape®SEED, extract from olive and grape seed, may be of clinical significance for the treatment of osteoarthritis By Elsa Mevel, Grap’Sud PhD Student Osteoarthritis (OA) is a major health concern that affects a growing part of the aging population and is associated with strong socio-economic burdens1, 2. The optimal treatment would consist in a therapy that can arrest the progressive degradation and the loss of articular cartilage and improve relief of symptoms such as inflammation and pain. However, so far there is no curative treatment for OA. It is well known that the inflammatory cytokines such as IL-1ß play important roles in OA3, 4. IL-1ß is thus well known to stimulate the synthesis of nitric oxide (NO), prostaglandin E2 (PGE2) and MMP-135, 6. Procyanidins (PCy) and hydroxytyrosol (HT), major bioactive polyphenols present in grape seed and olive, exert numerous health promoting effects counteracting inflammation, aging and cancer. In the light of these promising data we were interested in deciphering whether a combination of PCy

and HT, using OleoGrape®SEED, an extract from olive and grape seed, could have chondroprotective actions and, in a clinical perspective, conserve the bioactivity after oral consumption. Methods Human chondrocytes and cartilage explants were harvested from tibial plateau and femoral condyles of human cadavers to test whether PCy/ HT using OleoGrape®SEED can counteract IL-1ß effects. In these cellular models, the cytotoxicity was evaluated using a Methyl tetrazolium salt (MTS) assay. The products released (NO, PGE2 and MMP-13) were measured by the Griess method and by Enzyme-linked immunosorbent assay (ELISA), respectively. Then, the antiIL-1ß effects of PCy/HT metabolites found in sera after oral consumption were evaluated. For the in vivo study, rabbits (6 per groups) underwent a destabilisation of the right joint induced by anterior cruciate ligament transection (ACLT). OleoGrape®SEED

or vehicle (Veh) were administrated every two days by stomacal gavages for 13 weeks, starting 3 weeks before surgery. Knee OA severity was quantitatively assessed by X-ray blind evaluation using a homemade radiographic score performed by 2 independent readers. (continues on page 7 >>)

The biological quality of egg albumen As shown in the table, egg albumen has one of the highest quality scores compared with other protein types measured on these three parameters: Protein efficiency ratio: this parameter determines the effectiveness of a protein through the measurement of growth of rats as animal model. It measures the weight gain in grams per gram of protein. Values above 2.7 are considered as an excellent protein source. Biological value: a measurement of how efficient the body utilises protein consumed in a diet. A food with

a high value corresponds to a high supply of essential amino acids. Net protein utilisation: it is similar to the biological value except that it involves a direct measurement of retention of absorbed nitrogen. Net protein utilisation and biological value both measure the same parameter of nitrogen retention. However, the difference lies in that the biological value is calculated from nitrogen absorbed whereas net protein utilisation is from nitrogen ingested. Article 417

Protein efficient ration

Biological value

Net protein utilisation

Egg

3.9

100

Casein

2.5

Whey

3.2

104

Soy

2.2

Bean

0.0

Wheat gluten

0.8

Protein type

Source: Hoffman et al. (2004)

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Results Results indicated that OleoGrape SEED did not affect human chondrocytes viability under 10x concentration. Of interest, our data indicated that OleoGrape®SEED treatment significantly inhibited the IL-1ß-induced levels of the MMP-13, NO and PGE2 in isolated cultured chondrocytes (Fig. 1) as well as in the organ culture of human cartilage explants (Fig. 2). Moreover, sera collected from rabbits force-fed with extracts were found to exhibit an anti-IL-1ß effect in in vitro models of cultured chondrocytes (Fig. 3). X-ray of rabbits knees showed that OleoGrape®SEED decreased the ligament calcification, osteophytes formation, bone sclerosis and width of joint space narrowing associated ®

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with a significant decrease in the radiographic score compared to ACLT vehicle group (Fig. 4).

Conclusion To conclude, our data illustrated that OleoGrape®SEED counteracts the IL-1ß effects similarly in isolated chondrocytes and cartilage explants. Finally, HT and PCy were bioavailable and conserved their bioactivities in serum after oral consumption. We also provided in vivo evidence in post-traumatic OA model that OleoGrape®SEED exerts a modest but clearly noticeable effect on cartilage degradation. Taken together, these results suggest that OleoGrape®SEED may be of clinical significance for the OA treatment.

Figure 4: Effects of Oleogrape on ACLT rabbits model. Rabbits (n=6 per group) underwent ACLT of the right knee. Vehicle (Veh) or Oleogrape was administered every two days for 13 weeks starting 3 weeks before surgery, X-ray and radiographic score of lateral control (Ct) or ACLT rabbits treated with vehicle or Oleogrape at 10 weeks following surgery. *p>0.05 compared to ACLT receiving vehicle group.

Figure 1: Effects of Oleogrape on IL-1ß induced MMP, NO and PGE2 production in human chondrocytes. Cells were pre-treated with 10x concentration of Oleogrape 24h prior to IL-1ß (1mg/mL) 24. Data were expressed as relative MMP-13, NO and PGE2 productions compared to control condition (1ng/mL). *p<0.05 compared with cells stimulated with IL-1ß.

Figure 2: Effects of Oleogrape on IL-1ß induced MMP, NO and PGE2 production in human cartilage explants. Explants were pre-treated with 10x concentration of Oleogrape 24h prior to IL-1ß (1mg/mL) 24. Data were expressed as relative MMP-13, NO and PGE2 productions compared to control condition (1ng/mL). *p<0.05 compared with cells stimulated with IL-1ß.

Figure 3: Effects of sera from rabbits fed with Oleogrape on IL-1ß induced MMP, NO and PGE2 production in chondrocytes Rabbits (n=3 per condition) were fed with Oleogrape (100mg/kg) or saline solution (NaCl) every two days during 6 days and serum was harvested 2h after the last gastric gavage. Cells were pre-treated with serum from rabbits at a final concentration of 2.5% (v/v) 24 h pripr to IL-1B (1ng/mL) 24h. Data were expressed as relative MMP-13, NO and PGE2 productions compared to control condition (1ng/mL). *p<0.05 compared with cells treated with serum from rabbits fed with NaCl and stimulated with IL-1ß.

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The Alsiano Healthcare team Pharmaceuticals - cosmetics health & nutrition

Key accounts Anders Hager

Lene Aarøe Nissen

Annette Strarup

M.Sc. Chem. Sales director

B. Chem. Eng. Area sales manager

B.Sc. (Hons.) Chem. Eng. Area sales manager

E-mail: ahg@alsiano.com Tel. dir.: +45 8230 0026 Mobile: +45 2618 8545

E-mail: lan@alsiano.com Tel. dir.: +45 8230 0025 Mobile: +45 2270 1002

E-mail: ask@alsiano.com Tel. dir.: +45 8230 0049 Mobile: +45 2270 1015

Pharmaceuticals - cosmetics health & nutrition

Logistics Susse Liff Hansen

Lene Baldasano del Valle

M.Sc. Agriculture Area sales manager

Quality manager

Logistics manager

E-mail: haa@alsiano.com Tel. dir.: +45 8230 0009 Mobile: +46 708 155 012

E-mail: slh@alsiano.com Tel. dir.: +45 8230 0017

E-mail: lb@alsiano.com Tel. dir.: +45 8230 0015

Sales support Malene Rask Harder

Signe Mørck

Sales assistant

E-mail: mrh@alsiano.com Tel. dir.: +45 8230 0007

E-mail: sm@alsiano.com Tel. dir.: +45 8230 0042

References Nuesch E, Dieppe P, Reichenbach S, Williams S, Iff S, Juni P. All cause and disease specific mortality in patients with knee or hip osteoarthritis: population based cohort study. BMJ 2011; 342: d1165. 2. Leardini G, Salaffi F, Caporali R, Canesi B, Rovati L, Montanelli R. Direct and indirect costs of osteoarthritis of the knee. Clin Exp Rheumatol 2004; 22: 699-706. 1.

Goldring MB. The role of the chondrocyte in osteoarthritis. Arthritis Rheum 2000; 43: 1916-1926.

Kapoor M, Martel-Pelletier J, Lajeunesse D, Pelletier JP, Fahmi H. Role

Quality

Hedvig Åkesson

Sales support

Pharmaceuticals - cosmetics health & nutrition

of proinflammatory cytokines in the pathophysiology of osteoarthritis. Nat Rev Rheumatol 2011; 7: 33-42. Chabane N, Zayed N, Afif H, MfunaEndam L, Benderdour M, Boileau C, et al. Histone deacetylase inhibitors suppress interleukin-1beta-induced nitric oxide and prostaglandin E2 production in human chondrocytes. Osteoarthritis Cartilage 2008; 16: 1267-1274.

Mengshol JA, Vincenti MP, Brinckerhoff CE. IL-1 induces collagenase-3 (MMP-13) promoter activity in stably transfected chondrocytic cells: requirement for Runx-2 and activation by p38 MAPK and JNK pathways. Nucleic Acids Res 2001; 29: 4361-4372.

solutions based on innovation

Loeser RF, Goldring SR, Scanzello CR, Goldring MB. Osteoarthritis: a disease of the joint as an organ. Arthritis Rheum 2012; 64: 1697-1707.

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