Prehistory terminology

Probiotics/Prebiotics Lactulose

Food fibers Enterosorbents Lignin LactofiltrumLactofiltrum

Probiotics are beneficial bacteria that can be introduced into the digestive system with food. They enhance immunity, help regulate hormone balance, protect from food poisoning, allergies, and perform other important functions.

Prebiotics are non-digestible carbohydrates that pass through the small intestine undigested and are fermented in the colon by beneficial bacteria thus activating their growth.

Enterosorbents are substances that bind and deduce exogenous and endogenous toxins as well as pathogenic microorganisms and their metabolites from the gastrointestinal tract .

Composition

Medicinal lignin fibers, mg 375,0

 Lactulose, mg 125,0

 Moisture, % 5, 0

Total tablet weight, mg, + 5% 

500,0

Shelf life: 3 years

Lactofiltrum is patented in 1999. Expiry date 2019

Specification of components:

Medicinal lignin by Russian manufacturers standard (approved by the Ministry of Health) FSP 42-02363083-02

Lignin active substance and Lactofiltrum (as finished product) are manufactured on the own plant in accordance with GMP standards. Lignin modified preparation technology and sterilization were elaborated on the basis of the own patent (1999).

Lactulose (complies with Lactulose Concentrate USP26)

New generation prebiotic for elimination of intestinal pathogenic microorganisms and their toxins as well as for activation of own bifidobacteria growth, which normalizes microflora balance Dysbacteriosis of different etiology (gastro-

intestinal chronic and acute diseases, long-term therapy by anti-inflammatory non-steroids, immunosuppresants etc.)

Irritated bowel syndrome with a tendency to constipation and unstable stool

Rehabilitation of microflora disbalance after antibiotic therapy (incl. antibiotic-associated diarrhea)

In complex therapy of atopic dermatitis (diathesis) particularly in pediatric practice

Combined treatment of acute and chronic viral hepatitis and hepatic cirrhosis.

General improvement of intestinal microbiological ecology (for aging population)

Indications:

Dysbacteriosis or microflora disbalance

Vital aspects of abnormal microflora in children

Dysbacteriosis or microflora disbalance:

Microflora disorders are diagnosed in 90% children

Slows down vitamins and minerals absorption thus negatively affecting development of bone, muscle and nervous systems as well as immunity

Often causes or aggravates atopic dermatitis

Has negative destructive influence on the intestinal mucosa causing various gastro-intestinal chronic diseases

Vital aspects of normal microflora in adults and aged peopleNormal microflora

Prevents septic processes in intestines and colon

Results in decreasing internal intoxication

Improves absorption of vitamins and minerals preventing osteoporosis

Has beneficial effect on immunity and general physiological activity

FeaturesDOUBLE MECHANISM INFLUENCE ON MICROFLORA

Lactulose - improves growth and activity of lacto - and bifidobacteria

Lignin - natural enterosorbent, adsorbs wide range of endo- and exogenous toxins and pathogenic microorganisms in the intestines

100 %

Normalization of intestinal microflora

Аdvantages vs traditional probiotic therapy

LACTOFILTRUM®

(as prebiotic)

Bacterial colonies products (probiotics)

Direct absorption of pathogenic microflora and its toxins

Unable to absorb pathogens

Free transit through gastro-intestinal tract with minimum efficacy loss

Substantial loss of activity in intestines due to interference with aggressive stomach excretion

Direct stimulation of own normal microflora growth

Binds histamines and food allergens (in allergo-dermatosis

therapy) High safety profile: can be used for a long time without side

effects

Ideal as preventive (prophylactic) means

Indirect influence on the normal microflora growth

Unable to bind toxic organic metabolites

Restrictions for durable usage

Prophylactic usage with cautions

Сlinical evidence Treatment of dysbacteriosis in children,

including those with functional and chronic gastrointestinal disturbances

0

10

20

30

40

50

60

70

80

Lactofiltrummonotherapy

Standard therapy(spasmolitics,

probiotics)

constipation

abdom. pain

meteorism

Fig. 1 Improvement of clinical condition (treatment duration 14 days)

Effi

cacy

, % p

atie

nts

Research Institute of Pediatrics (Moscow, 2003)

Lactofiltrum influence on intestinal microflora

Microflora compositionNormal

level

With Lactofiltrum (n = 45)

Control (n = 15)

Before After Before After

Bifidobacteria > 8 < 6 > 9 < 7 < 7

Lactobacteria > 6 < 5 > 8 < 5 6

E.coli, weak fermentative < 10 % 13% 5% 12% 9%

Hemolytic E.coli 0 5 0 6 2

Candida < 3 > 5 0 > 5 < 4

Lactase-negative bacteria < 5 % 7% 3% 7% 5%

Enterococcus < 7 > 9 < 3 > 8 < 3

Fig. 2

Research Institute of Pediatrics (Moscow, 2003)

DOSAGES:

Children under 6 months - 1/4 tablet 3-4 times a day

6 months - 1 year - 1/3 tablet 3-4 times a day

1-3 years - 1/2 - 1 tablet 3 times a day

4-7 years - 1 - 1,5 tablets 3 times a day

over 7 years - 2 tablets 3-4 times a day.

1-1,5 hours before or 1-1,5 hours after meal.

Lactofiltrum treatment resulted in normalization of intestinal microflora composition, namely, in elimination of opportunistic bacteria, suppression of cocci and growth of Lacto- and Bifidobacteria.

CONCLUSIONS

Сlinical evidence

CONCLUSIONS (cont.)

Lactofiltrum corrects both intestinal peristalsis and intestinal microflora composition.

Lactofiltrum is effective in pediatric patients with functional gastrointestinal disturbances like

Lactofiltrum can be used for conditioning therapy to enhance the effect of further decontamination against parasitic invasion (lambliasis)

Lacto- and Bifidobacteria-containing drugs can be reasonably used after 14-day conditioning by Lactofiltrum.

At least 14-day treatment by Lactofiltrum with further analysis of feces for dysbacteriosis appears obligatory after children are transferred from hospital to an orphanage. This measure aims at prevention of nosocomial infection in weak children by opportunistic microflora.

Lactofiltrum clinical study in patients with dysbacteriosis Dynamics of clinical symptoms during Lactofiltrum treatment

0%

20%

40%

60%

80%

100%

120%

Beforetreatment

1-st week oftreatment

2-nd week oftreatment

Appetite

Meteorism

Constipation

Unstable stool

RESULTS:

Improvement of clinical signs was associated by alleviation of intestinal dysbacteriosis.

State Medical University (Saratov, 2005)

0

2

4

6

8

10

12

14

skin hyperemia skin pruritis skin dryness

Lactofiltrum + standardtherapy

Standard therapy (diet,antihistamins, topicals,enzymes)

Conclusions:

Lactofiltrum can be recommended for monotherapy of mild atopic dermatitis in the phase of incomplete remission of moderate disease, and for treatment of moderate atopic dermatitis in combination with local therapy.

Atopic dermatitis accompanied by intestinal disturbance with a tendency to constipation and unstable stool

Treatment duration 14 daysDays

Scientific Center of Children Health (Moscow, 2003)

Acute viral hepatitis (A, B, C)

02468

1012

Lactofiltrumtreatment

Control group

Duration of the major clinical signs

Lactofiltrum addition to standard therapy of acute viral hepatitis results in significantly lesser duration and intensity of intoxication (fatigue, headache, low appetite, anorexia, fever), dyspepsia, pain and jaundice. Such

treatment is shown to accelerate normalization of liver and thickened gallbladder wall sizes and gallbladder clearance of the solids compared to control patients.

Federal Medico-Biological Agency (Moscow, 2005)

Days

Treatment duration 21 days

0

1

2

3

4

5

6

7

8

1 2 3 4

0

1

2

3

4

5

6

7

8

1 2 3 4

Intestinal microflora components in patients with genitourinary chlamydiosis (lg CFU/g).

Control group: clarithromycin Experimental group: clarithromycin + Lactofiltrum

Before treat.

After treat.

1 - Lactobacillus spp.

2 - Bifidobacterium spp.

3 - Escherichia coli4 - Enterococcus spp.

Microflora support during oral antibacterial therapy

Institute of Epidemiology and Microbiology (St.-Petersburg)

RESULTS• Decrease of lactobacilli and bifidum bacteria content was statistically significant in the control group (р<0.001 and p< 0.05 respectively).• Analysis did not reveal significant qualitative alteration of the studied microflora components in experimental patient group.

CONCLUSIONS

1. The study confirmed the efficacy of prebiotic Lactofiltrum administration for prevention of dysbacteriosis development during chlamydiosis treatment by macrolide antimicrobial clarithromycin.

2. Lactofiltrum administration concomitantly with antimicrobial treatment of chlamydiosis facilitates preservation of normal intestinal microflora and decreases the risk of intestinal colonization by Candida spp.

3. Lactofiltrum administration decreases the risk of antimicrobials-induced dyspepsia and allergic reactions.

Lactofiltrum prevention of intestinal dysbacteriosis in surgical patients with purulent conditions receiving prolonged antimicrobial therapy (by CEPHAZOLIN, IMIPENEM, MAXIPIME)

Dysbacteriosis parameters

Study group Control group

Before treatment

After treatment

Before treatmen

t

After treatmen

t

Bifidobacteria (<107) 10% 5% - 20%

Lactobacteria (<105) 5% 5% - 30%

Lactose-negative E. coli (> 5%) 5%   - 50%

E. coli with low enzyme activity (> 10%) 10% 5% - 30%

Hemolytic E. coli 5%   - 40%

Proteus spp. (>103) 10%   - 30%

Staphylococcus aureus 20%   - 40%

Military hospital №42 (St.-Petersburg)

Microflora support during parenteral antibacterial therapy

RESULTS

Potential prolonged antimicrobial therapy results in intestinal dysbacteriosis, decrease of bifidobacteria and lacrobacteria content and appearance of opportunistic and pathogenic microflora, including Candida spp.

Lactofiltrum administration allows prevention of intestinal dysbacteriosis during antimicrobial therapy.

Lactofiltrum administration decreases the risk of Candidosis development during antimicrobial therapy.

Lactofiltrum administration allows normalization of gastrointestinal tract condition even in patients with initial dysbacteriosis – normalization of microflora profile, stool frequency and consistence, pain, discomfort and meteorism relief.

CONCLUSION Lactofiltrum inclusion into combined therapy schedule significantly

alleviates both clinical and laboratory manifestations of dysbacteriosis during prolonged parenteral antimicrobial therapy.

Sales dynamics, Russia

0

200 000

400 000

600 000

800 000

1 000 000

1 200 000

1 400 000

packs N60

2001 2002 2003 2004 2005 2006

Positioning: key messages aspects

Double power prebiotic for improvement of

intestinal microflora in case of gastrointestinal

disorders and atopic dermatitis High safety profile prebiotic for all groups of

population Microflora protector during antibiotic therapy Strengthens standard therapy efficacy in case of

microflora disorders (synergy)

R & D prospectsR & D prospects

Product improvement for children audience: confectionery, powders, various tastes

Miscellaneous formulations: caplets, capsules, sache, gel, paste

Combination with additives giving synergy positive effect for intestinal microflora

Modifying prebiotic component to reach better activation of definite spp.

Modifying enterosorbent component to gain more specific absorption of certain pathogens

Representação no Brasil:

R. Dr. Cândido Espinheira, 350 – 13° andar – Cj. 132

CEP 05004-000 – São Paulo/SP

Fone 55 11 3676-0546 / FAX 55 11 3676-0559

chemitex@chemitex.com.br