Technical Description

Refined and Standardized dry Extract produced from Bilberry Fruit Fresh

Appearance Dark reddish-violet, amorphous hygroscopic powder

Storage Preserve in tight container, protected from light, heat and humidity

Bibliografic References

1. Monograph. Vaccinium myrtillus (Bilberry). Altern Med Rev. Oct;6(5):500-4. (2001)2. Anthocyanosides and microvessel walls: new findings on the mechanism of action of their protective effect in syndromes due to abnormal capillary fragility. Minerva Med;68(52):3565-3581 (1977). Mian E.3. Anthocyanins in Cardiovascular Disease. Developing Solutions, LLC, Washington, American Society for Nutrition. Adv. Nutr. 2: 1–7 (2011). Taylor C. Wallace4. Effects of Mirtogenol on ocular blood flow and intraocular hypertension in asymptomatic subjects. Mol Vis (2008);14:1288-1292. Steigerwalt, R. D., Gianni, B., Paolo, M., Bombardelli, E., Burki, C., and Schonlau, F.5. Anthocyanosides in the treatment of retinopathies. 1981 May;178(5):386-9. Scharrer A, Ober M. Klin Monbl Augenheilkd.6. Monitoraggio perimetrico di soggetti miopi in trattamento farmacologico a lungo termine con un’associazione tra antocianosidi e vitamine. Boll. Ocul. 1990, 69 (1), 57-71. Gandolfo E.Natural Therapies for Ocular Disorders Part Two: 7. Cataracts and Glaucoma. Altern Med Rev. 126: 10619-10631. Kathleen Head, ND (2004).8. Diabetic and hypertensive retinopathy therapy with Vaccinium myrtillus anthocyanosides (Tegens). Double blind, placebo-controlled clinical trial. Ann Ottalmol Clin Ocul 1987;113:1173. Perossini M, et al.9. Diabetic cataracts and flavonoids. Science 1977;195:87-89. Varma SD, Mizuno A, Kinoshita JH.10. Studies on Vaccinium myrtillus anthocyanosides. I. Vasoprotective and anti-inflammatory activity. Arzneim Forsch 1976;26:829-832. Lietti A, Cristoni A, Picci M.11. Anthocyanin supplementation improves serum LDL- and

HDL-cholesterol concentrations associated with the inhibition of cholesteryl ester transfer protein in dyslipidemic subjects. Am J Clin Nutr.; 90(3): 485-92. Epub 2009 Jul 29. Qin Y, Xia M, Ma J, Hao Y, Liu J, Mou H, Cao L, Ling W (2009).12. Effects of Vaccinium myrtillus anthocyanosides on arterial vasomotion. Arzneim Forsch 1991;41:905-909. Colantuoni A, Bertuglia S, Magistretti MJ, Donato L.13. Contributo al trattamento delle flebopatie da stasi in gravidanza. Minerva Ginecol. 1980, 32, 1-10. Grismondi G.L.14. Antiulcer and healing activity of Vaccinium myrtillus anthocyanosides. 1987 Feb;42(2):29-43. Cristoni A, Magistretti MJ. Farmaco Prat.15. Gli antocianosidi da Vaccinium Myrtillus nella cura delle flebopatie da stasi degli arti inferiori. Gaz. Med. It. 1980, 139, 217-224. Tori A.16. Molecular Mechanisms Behind the Chemopreventive Effects of Anthocyanidins. J Biomed Biotechnol. (5): 321–325 (2004). De-Xing Hou, Makoto Fujii, Norihiko Terahara, and Makoto Yoshimoto.17. Antioxidant capacity as influenced by total phenolic and anthocyanin content, maturity, and variety of Vaccinium species. J Agric Food Chem. 46: 2686- 93. (1998) Prior RL, Cao G, Martin A, Sofic E, McEwen J, O’Brien C, Lischner N, Ehlenfeldt M, Kalt W, Krewer G and others.18. Bilberry juice modulates plasma concentration of NF-kappaB related inflammatory markers in subjects at increased risk of CVD. Eur J Nutr. 2010 Sep;49(6):345-55. Karlsen A, Paur I, Bøhn SK, Sakhi AK, Borge GI, Serafini M, Erlund I, Laake P, Tonstad S, Blomhoff R

Linnea SA Via Cantonale CH-6595 Riazzino (TI) Switzerland Tel: +41 (0)91 850 5050Fax: +41 (0)91 850 5070 E-Mail: info@linnea.ch Web: www.linnea.ch

Linnea Inc 435 McCartney Street Easton, PA 18042

Tel: 888-253-0044 (US) or +1 610-253-7950Fax: +1 610-253-7970E-mail: dstanek@linnea.chWeb: www.linnea-us.com

BILBERRY FRUIT DRY EXTRACT

EP USP

TLC Identification Complies Complies

ASSAY (HPLC)

(dry basis)

32.4 % to 39.6% of Anthocyanins

expressed as cyanidin 3-O-

glucoside chloride

≥ 36.0 % of Anthocyanins expressed

as cyanidin 3-O- glucoside chloride

Total anthocyanidins (HPLC) NMT 1.0 % NMT 1.0 %

Water content NMT 4.5 % (LoD) NMT 4.5 % (KF)

Ash NMT 2.0 % (Total Ash) NMT 3.0 % (Sulphated Ash)

Heavy metals NMT 20 ppm NMT 20 ppm

Microbiology Complies with Harmonized

Pharmaceutical Method

Complies with Harmonized

Pharmaceutical Method

Residual solvents Complies with ICH standard Complies with ICH standard

Contaminants According to current legislations

BILBERRY ETHANOL EXTRACT

HPLC 36% UV 25%

TLC Identification Complies Complies

ASSAY

(dry basis)

HPLC ≥ 36.0 % of Anthocyanins

expressed as cyanidin 3-O-

glucoside chloride

UV ≥ 25.0 % of Anthocyanins

expressed as cyanidin 3-O-

glucoside chloride

Water content NMT 4.5 % NMT 4.5 %

Sulphated Ash NMT 3.0 % NMT 3.0 %

Heavy metals NMT 20 ppm NMT 20 ppm

Microbiology Complies with Harmonized

Pharmaceutical Method

Complies with Harmonized

Pharmaceutical Method

Residual solvents Complies with ICH standard Complies with ICH standard

Contaminants According to current legislations

Bilberry Fruit Dry Extract (EP, USP)Bilberry Ethanol Extract (36% HPLC, 25% UV)

Common Applications and Evidence

Eye health and vision improvement

Taken orally, Bilberry extract improves visual acuity in healthy individuals and it is a valid support in the treatment of eye

diseases such as cataracts, macular degeneration, retinitis pigmentosa, glaucoma and myopia. [4,5,6]

In severe eye diseases (retinopathy, glaucoma and toxic amblyoplia), anthocyanosides mitigate retinal vessel abnormalities

and help to prevent visual field disorders [6,7,8]. They are effective in preventing and inhibiting the development of

the early stages of diabetic retinopathy [8,9]. Significant improvements have been observed in ophthalmoscopic and

angiographic parameters of patients receiving Bilberry for one month [8,9].

Vasoprotective activity

Epidemiological investigations have indicated that anthocyanin consumption through the intake of products such as

bilberry juice, red wine or Bilberry extract reduces the risk of cardiovascular diseases [10,11].

Bilberry preparations are used in the prevention and as adjuvants in the treatment of vascular and blood disorders

such as varicose veins, thrombosis and angina. [12,15]

Clinical trials have shown improvements in patients with lower limb varicose veins, thocyanosides had a vasoprotective

effect, combating reduced capillary resistance symptoms such as petechiae, bruising and faecal occult blood [10, 11,12,13].

Antiulcer and astringent activity

For its content in Tannins, bilberry extract is used as astringent and to treat diarrhoea. In animal models of gastric ulcers,

cyanidin chloride contained in Bilberry extract showed antiulcer activity. [14]

Bilberry extract is used against haemorrhoid of pregnant women as totally natural product [13], it is also used in

ENT surgery to reduce intra-and post-operative bleeding and to prevent the onset of haemorrhagic complications, by

reducing the idiopathic epistaxis caused by abnormal capillary fragility [14,15].

Free radical scavenging, antioxidant and chemopreventive activities

Anthocyanins have demonstrated an inhibitory effect on the growth of some cancer cells and, due to their global

chemoprotective effect, they are recommended in the prevention of a range of diseases (atherosclerosis,

cardiovascular disease and chronic inflammation) [10, 16].

Bilberry extract plays an important role in protecting against restraint stress-induced liver damage by both scavenging

free radicals and inhibiting lipid peroxidation. [10,16]

Free radical quenching activity has been determined by the ORAC test measuring the antioxidant capacity. Bilberry

exhibited the most potent antioxidant activity (44.6 ± 2.3) among different berries species. [16, 17,18]

Linnea extract is obtained exclusively from the fruits of shrubs native to the wilds of Northern and Eastern European

Countries, which are recognized to have the most effective active substance composition.

Fruits are widely harvested and checked carefully prior to shipment. Bilberries fruits are soft and juicy and thus highly

susceptible to damage. Linnea staff is present on site to monitor all procedures involved in harvesting, cleaning,

refrigerating, storing and transporting the fruits and to guarantee raw material quality from harvest to delivery.

Source

BILBERRY

Vaccinium myrtillus is a small deciduous shrub belonging to the Ericaceae family. The genus Vaccinium comprises

almost 200 species which are most commonly found in Europe, Asia and Northern America. European Bilberry grows

wild to a height of six to twenty-four inches and often forms large, dominant colonies.

Activity

Bilberry extract contains anthocyanosides, tannins and flavonoids that have been largely studied for their antioxidant

effects protecting against free radical damage. [1]

Anthocyanins and other phenolics from bilberry up-regulate defences against oxidative stress, influencing genes

controlled by the antioxidant response element [2], inhibiting the enzymes that cause the degradation of collagen fibres

and promoting biosynthesis. The resulting effect is the decrease in capillary permeability and fragility and the inhibition

of platelet aggregation. Bilberry constituents prevent the release and synthesis of pro-inflammatory compounds. [1,2,3]

The documented effect on night vision is mainly related to the recovery of rhodopsin, which improves ocular blood

flow and lowers intraocular pressure, favourably modifying several enzymatic parameters involved in retina damage. [4]

HPLC profile of Bilberry extract shows a typical fingerprint characterized by the 15 major constituents.

Linnea Bilberry EP EP Bilberry Standard

Name of the plant Vaccinium myrtillus

Part of the plant used Berries

Structural Formula

Bilberry fingerprint

Cyanidin 3-O-glycoside R=R1=OH; R2=H

Delphinidin 3-O-glycoside R=R1= R2=OH

Malvidin 3-O-glycoside R=R2=OMe; R1=OH

Peonidin 3-O-glycoside R=OMe, R1=OH; R2=H

Petunidin 3-O-glycoside R=R1=OH; R2= OMe

R3= arabinose or glucose or galactose

Bilberry Fruit Dry Extract (EP, USP)Bilberry Ethanol Extract (36% HPLC, 25% UV)

1

100

90

80

70

60

50

40

30

20

10

0

10 25 4015 30 4520 35 50

2

4

5

6

7

8

910

11

12

13

14

15

1617 18

1920

3

0.100

0.090

0.080

0.070

0.060

0.050

0.040

0.030

0.020

0.010

0.000

5.00 20.00 35.0010.00 25.00 40.0015.00 30.00 45.00 50.00

1 2

34 5

6

78

910

11

1213

14

15

16

17

18 1920