Pharma & Healthcare News October 2015

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Contents

Lynside Pro GI+ becomes ibSium .....................................1

Xylitol and erythritol fordirect compression .................2

New KitoZyme study completed with promisingresults ......................................3

MICROCEL® Microcrystalline cellulose ..................................4

Egg albumen protein is an effective protein source ........5

OleoGrape®SEED - powerfulantioxidant .............................6

The Alsiano Healthcareteam .......................................8

No. 21 • October 2015

Pharma & Healthcare News Alsiano

Publisher: Alsiano A/SCirculation: 550 copies

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.

Lynside Pro GI+ becomes ibSiumThe all-natural long-term solution from Lesaffre Human Care to reduce abdominal pain and dis-comfort is currently being rebranded as ibSium. Same innovative ingredient – now stronger identity

Aiming at increasing visibility and rais-ing 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 prod-uct 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 ingredi-ent 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 Na-tional Collection of Microorganism Cultures as CNCM¬3856.

• An innovative and natural ingre-dient which has demonstrated a significant effect relieving abdomi-

nal pain and discomfort of indivi-duals with irritable bowel syn-drome (IBS) through

- 2 clinical studies on a total of 600 volunteers with IBS and conducted by independent experts in Gastro-enterology

- 1 consumer study implemented in collaboration with prescribing phy-sicians on more than 1160 volun-teers 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 considera-tion for long-term use.

• Fast-acting solution with signs of improvement felt within the first few days of consumption.

Health claim for ibSium in Canada- read more on p.2.

(continues on page 2 >>)

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FoodNews No. 1 • February 2004 AlsianoPharma & Healthcare News No. 21 • October 2015 Alsiano

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Health claim for ibSium in CanadaBased 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.

• EU QPS (Qualified Presumption of Safety) microorganism and US GRAS (Generally Recognized as Safe) status.

In a nutshell, ibSium is a natural al-ternative to prescription drugs often used in intestinal pain and discomfort management. ibSium can be consid-ered as a safe and efficient innova-tive strategy for long term use in im-proving the quality of life of people suffering from digestive disorders by easing their symptoms.

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

Xylitol and erythritol for direct compressionFutaste erythritol and xylitol contribute effective compaction properties within specific tableting applications and usages

Europe products can provide the de-sired texture, appearance and dos-age combined with mouthfeel and sweetness flavour which are key components of various formulations.

Futaste Europe offers direct compres-sion 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 excep-tional sweetness and providing fla-vour improvement.

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

Low and almost zero calorieErythritol and xylitol can offer tablet-ing processors potential to utilise a low kcal product and almost zero kcal too if erythritol is chosen. The Futaste

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 opportuni-ties 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

For further information please con-tact Alsiano.

been accepted for publication in the renowned peer-reviewed “United Eu-ropean 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 be-comes the best substantiated natural ingredient with a clinically proven ef-fect on IBS symptoms.

Article 413

Article 414

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Pharma & Healthcare News No. 21 • October 2015 Alsiano

Article 415

The unique nature of KitoZyme’s chitosanKiOnutrime-CsG is a unique natural fibre extracted from fungi using a patented proc-ess developed by KitoZyme. It dissolves in 10 minutes in the acidic environment of the stom-ach. That means that a dose can be administered almost im-mediately 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.

New KitoZyme study completed with promising resultsA new clinical study involving around 100 persons has demonstrated excellent results achieved with KiOnutrime-CsG, which helps combat excess weight and obesity

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

By KitoZyme

KitoZyme operates in three segments of the healthcare sector: digestive health, weight management and car-diovascular health. The study related to a product within weight mana-gement has just been completed. More specifically, the objective was to verify and demonstrate the reduc-tion in bodyweight in overweight and obese subjects as a result of the lipid-absorbing 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 statis-tically significant reductions in body fats and abdominal, hip and waist measurements in people who took

Patients recorded a clear, progressive reduction in their weight”

people in the treatment group were given five capsules per day, each con-taining 500 mg of KiOnutrime-CsG. The 32 people enrolled in the control group followed the same procedure but their capsules contained a place-bo. All patients maintained their usu-al eating habits and did not change their lifestyle.

Weight loss was on average 3.2 kg in the group receiving treatment.

The clinical trial requirements in detailThe multicentre clinical trial took place in four hospitals and medical research centres between the end of 2014 and the start of 2015. A to-tal 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

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MICROCEL® from Blanver is the preferred excipient for use in tablets, capsules, granules, pellets and spheres

MICROCEL® Microcrystalline Cellulose

Microcrystalline Cellulose (MCC) is a partially depolymerised pure cel-lulose. Its appearance is a white, in-soluble, odorless and tasteless pow-der, 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

ApplicationsMICROCEL® 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 applica-tions shown in the table below.

MICROCEL® types for each manufactured processThe MICROCEL® range consists of four different types. The range of recommended levels of use for all ap-plications for the four types, either in wet granulation or in direct compres-sion, is usually between 10 and 90%. Each type is able to function in the following manufacturing processes:

MICROCEL® 101: Wet Granulation, API Adsorption/Absorption, Vegeta-ble Extract Adsorption/Absorption and Pellet & Spheronisation;

Tablets for direct compression

Tablets by wet granulation

Capsules (automatic machine)

Capsules (semi-auto-matic machine

Granules

Pellets and spheres

API adsorption

API absorption

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

Reduce

s fria

bility

Binder

agen

tFlo

w aid

Disinteg

rant &

Diluen

t

Facili

tates

additio

n of

Carrier

for d

rugs

Oil adso

rption

Vegeta

ble ex

tract

Facili

tates

extru

sion


MICROCEL® 102: Wet Granulation, Direct Compression, API Adsorption/Absorption, Vegetable Extract Ad-sorption/Absorption, Capsule (Auto-matic Filling);

MICROCEL® 12 & 200: Direct Com-pression, Poor Flowing APIs, API Ad-sorption/Absorption, Vegetable Ex-tract Adsorption/Absorption, Capsule (Semi-Automatic Filling).

Regulatory Information

CAS: 9004-34-6DMF (US FDA): 9201

Compressio

n

dissolutio

n aid

carrie

r

in liquid fo

rm

granulat

ion solutio

nMICROCEL®

applications

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Egg albumen protein is an effective protein sourceEAP-Sport from Pulviver offers an alternative protein source with high biologi-cal 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 proteinsEgg 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 animalorigin, its amino acid composition is comparable with whey protein con-centrate.

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

BLANVER is a global leader with more than 30 years of experience in the production of excipients for the pharma-ceutical, food and cosmetic in-dustries.

Blanver products comply with the highest quality standard and are present in various for-mulations in more than 100 countries worldwide.

MICROCEL®

comparative characteristics

Differential analysis

Average particle size (microns)

Retained on 60 mesh (%)



Loss on drying (%)

Bulk density (g/cm3)

101

50

NMT 1

-

NMT 30

NMT 7

0.26-0.31

102

100

NMT 8

-

NLT 45

NMT 7

0.28-0.33

12

160

NLT 10

NLT 40

-

NMT 7

0.30-0.40

200

180

NLT 10

NLT 50

-

NMT 7

0.33-0.44

NMT = No More Than - NLT = No Less Than

Article 416


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*calculated on dry matter content; Kjeldahl N x 6.25)

Types

• 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

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OleoGrape®SEED - powerful antioxidantA 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 associ-ated with strong socio-economic bur-dens1, 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 inflamma-tion and pain. However, so far there is no curative treatment for OA.

It is well known that the inflamma-tory cytokines such as IL-1ß play im-portant 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), ma-jor bioactive polyphenols present in grape seed and olive, exert numer-ous health promoting effects coun-teracting inflammation, aging and cancer. In the light of these promising data we were interested in decipher-ing 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, con-serve the bioactivity after oral con-sumption.

MethodsHuman chondrocytes and cartilage explants were harvested from tibial plateau and femoral condyles of hu-man cadavers to test whether PCy/HT using OleoGrape®SEED can coun-teract IL-1ß effects. In these cellular models, the cytotoxicity was evalu-ated using a Methyl tetrazolium salt (MTS) assay. The products released (NO, PGE2 and MMP-13) were meas-ured by the Griess method and by Enzyme-linked immunosorbent assay (ELISA), respectively. Then, the anti-IL-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 in-duced by anterior cruciate ligament transection (ACLT). OleoGrape®SEED

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 pa-rameter determines the effectiveness of a protein through the measure-ment 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 excel-lent protein source.

Biological value: a measurement of how efficient the body utilises pro-tein consumed in a diet. A food with

or vehicle (Veh) were administrated every two days by stomacal gavages for 13 weeks, starting 3 weeks be-fore surgery. Knee OA severity was quantitatively assessed by X-ray blind evaluation using a homemade radio-graphic score performed by 2 inde-pendent readers.


Article 417

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Egg

Casein

Whey

Soy

Bean

Wheat gluten

Net protein

utilisation

Source: Hoffman et al. (2004)

Protein efficient ration

Biological value

Protein type

3.9

2.5

3.2

2.2

0.0

0.8

100

77

104

74

-

64

94

76

92

61

0

67

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 para- meter of nitrogen retention. How-ever, the difference lies in that the biological value is calculated from ni-trogen absorbed whereas net protein utilisation is from nitrogen ingested.

The biological quality of egg albumen

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ResultsResults indicated that OleoGrape® SEED did not affect human chondro-cytes viability under 10x concentra-tion. Of interest, our data indicated that OleoGrape®SEED treatment sig-nificantly 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

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

ConclusionTo conclude, our data illustrated that OleoGrape®SEED counteracts the IL-1ß effects similarly in isolated chondrocytes and cartilage explants. Finally, HT and PCy were bioavail-able and conserved their bioactivi-ties 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.

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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 com-pared 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 chondrocytesRabbits (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.

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 be-fore 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.

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The Alsiano Healthcare team

Key accounts

Anders Hager

M.Sc. Chem.Sales director

E-mail: [email protected]. dir.: +45 8230 0026Mobile: +45 2618 8545

Pharmaceuticals - cosmeticshealth & nutrition

Annette Strarup

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


Lene Baldasano del Valle

Logistics manager

E-mail: [email protected]. dir.: +45 8230 0015

Logistics


Lene Aarøe Nissen

B. Chem. Eng.Area sales manager


Malene Rask Harder

Sales assistant


Sales support

Signe Mørck

Sales assistant


Sales support

Hedvig Åkesson

M.Sc. AgricultureArea sales manager

E-mail: [email protected]. dir.: +45 8230 0009Mobile: +46 708 155 012


Susse Liff Hansen

Quality manager


Quality

Article 418

>>7. Loeser RF, Goldring SR, Scanzello CR, Goldring MB. Osteoarthritis: a dis-ease of the joint as an organ. Arthritis Rheum 2012; 64: 1697-1707.

References1. 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: popu-lation based cohort study. BMJ 2011; 342: d1165.2. Leardini G, Salaffi F, Caporali R, Cane-si B, Rovati L, Montanelli R. Direct and indirect costs of osteoarthritis of the knee. Clin Exp Rheumatol 2004; 22: 699-706.

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

4. Kapoor M, Martel-Pelletier J, Lajeu-nesse D, Pelletier JP, Fahmi H. Role

of proinflammatory cytokines in the pathophysiology of osteoarthritis. Nat Rev Rheumatol 2011; 7: 33-42.

5. Chabane N, Zayed N, Afif H, Mfuna-Endam L, Benderdour M, Boileau C, et al. Histone deacetylase inhibitors sup-press interleukin-1beta-induced nitric oxide and prostaglandin E2 production in human chondrocytes. Osteoarthritis Cartilage 2008; 16: 1267-1274.

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

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Pharma & Healthcare News October 2015