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Throat infection – more

Launched or under launch (2013-2015): France, Australia, Colombia, Czech Republic + Slovakia, Denmark, Dubai, Egypt, Finland, Hungary, Israel, Jordan, Malaysia, Middle East, New Zealand, Poland, Portugal, Romania, Serbia, South Africa, Spain, Tunisia, Turkey…

Throat Infections

30mL adult or 20mL kid Sprays For the treatment of Throat Infections
(Official Indication) Preventive &/or Curative

Throat infection (Adult & Kids)

Throat infection starts when viruses (influenza or rhinovirus) attack throat cells, grow inside the cells, cause cell death, and liberate a huge amount of new virus on the throat surface (outside the cells) that start attacking & killing more & more cells. Opportunist bacteria grow, stick to the damaged throat surface and cause further cellular damage, and the signs of sore throat then appear. To fight the infection, the body  reacts by secreting pro and anti-inflammatory cytokines, which causes pain, irritation & itching. If the infection continues, the concentration of pro-inflammatory cytokines exceeds that of anti-inflammatory proteins & sore throat persists.

An ideal treatment should be topical to avoid side effects. It should stop new virus infection by preventing virus entry into the cells, detach bacteria, and clean the throat surface of all the contaminants to restore normal cellular defense functions. The treatment should also block pro-inflammatory proteins to stop pain & irritation. In addition, an effective treatment must be totally safe and cell-friendly (non-chemical) and fast acting.

Conception of VITROBIO sore throat spray

  1. Highly osmotic film to clean the throat surface: The film was conceived using polymeric VB-Gy: a highly osmotic filmogen solution as described in the patent PCT/FR99/01340. Applying such a film on an infected throat surface creates an instant & strong exudation of hypotonic liquid from the inner parts of the throat surface, thereby detaching and draining away all the contaminants. Cleaning the throat surface offers instant symptomatic relief by reducing pain, irritation & itching.
    What can be claimed: Instant and long-lasting mechanical throat cleaning.

 

  1. Anti-cytokine polymers to suppress inflammation: The concentration of undesired proteins varies according to the location, chronicity, and the type of insult to the body. TNF-α, IL-1β, IL-6 and IL-4 are the main inflammatory proteins found on inflamed throat surfaces. A completely novel approach consisting in blocking free proteins using polymers was deployed to neutralize these cytokines & thus suppress inflammation.

To evaluate cytokine – polymer binding, each cytokine was incubated with specific polymers for 5 min. The concentration of free cytokine was then quantified by ELISA (Enzolife sciences) or AlphaLISA (PerkinElmer). Polymers showing statistically significant binding with selected cytokines were then tested in association to obtain maximum inhibitory response. These polymers were then incorporated in the final product composition.

Results indicated that only a few polymers bind to proteins, this binding is specific and varies considerably according to the structure, length & concentration of polymer(s) used, as well as the pH & the filmogenicity of the medium in which polymers are suspended.

As shown in the example of polymer –cytokine binding figure above, the best polymers or their associations incorporated in the final throat spray formulation are capable of binding and neutralizing between 50-75% of inflammatory cytokines within 5 min of contact. Longer contact time further improves their binding.

What can be claimed? Pain relief & anti-inflammatory effects within 5 minutes.

 

  • 3. Antiviral polymeric association to neutralize free virus particles:

Virus envelops contain, on their surface, specific proteins (glycoproteins) which help virus attachment to host cells, leading to virus entry, growth & multiplication inside the host cells. Examples of virus surface proteins are H1N1 (hemagglutinin & neuraminidase) on influenza and parainfluenza viruses, G protein on RSV virus, vmw65 & HHV capsid portal protein on Herpes virus, VP-1, 2, 3, 4 on rhinovirus, & HIV-1 proteases on HIV virus. Intensive research on antiviral therapy is currently underway but, still, there is no topical antiviral drug available. Cyclovirs (Zovirax) & neuraminidase inhibitors (Tamiflu) are intracellular virus growth inhibitors, whereas in all topical virus infections (influenza, rhinovirus, herpes), millions of free virus particles are present on the infected surface, where a systemic drug cannot reach. These drugs acting intracellularly, their benefit/risk ratio is too poor to be used for the treatment of non-life threatening viral infections.

VITROBIO envisaged a completely new hypothesis consisting in trapping free virus particles on the surface of the injury using specific polymers having affinity for target virus glycoproteins. Being topical, this approach is totally safe without any probability of side effects or cellular interactions. Once bound by polymers, viruses cannot enter the cells anymore and further infection is thus stopped.

Selection of antiviral polymers: Polymer – protein binding is highly specific and infrequent. Natural polymers, extracted using different methods, were incubated for 1h with a fixed concentration of virus to allow polymer – virus protein binding. Host cells (Vero, MDBK, MDCK, multicellular skin epithelial cells) were exposed to the virus and virus titer was measured. Reduction in virus-infected cell death compared to corresponding controls was calculated to evaluate virus neutralization. An example of best results obtained with individual polymers or associations of polymers for influenza virus growth on MDCK cells is shown below:

Results show that Czl1, VB-AX, & Rsn5 polymers can neutralize up to 50% influenza virus while polymers Gdm6, Vev6 & Sen5 (individually)neutralized only between 25-40% virus, but 98.5% virus can be neutralized when these 3 polymers are associated. Based on these results (report VB-44a), a specific association of polymers was incorporated in filmogen osmotic solution to maximize anti-inflammatory and anti-viral effects of the final formulation.

What can be claimed? Neutralizes 98.5% free influenza virus within 1h.

In addition to Filmogen VB-Gy + anti-inflammatory + anti-viral polymers, the final formulations may also contain some honey as dilution of honey with the osmotically attracted hypotonic liquid generates H2O2 bubbles. These air bubbles attach to hidden bacteria & the contaminant is then removed along with the air bubble. Some preparations may also contain essential oils to improve the smell (&/or sensation) of the product and to render it hydrophobic, thereby minimizing its dilution with the hypotonic liquid outflow.

CLINICAL EFFICACY

Formula 1: Pilot Clinical Study

 

Study Design: “Open label, multicentric pilot study to assess the efficacy and safety of VB Throat Spray formulation against standard treatments in subjects suffering from severe acute sore throat infection” conducted according to ICH-GCP guidelines.

CRO: NEXUS Clinical Research LLC USA, Ithaca NY & Subsidiary NEXUS Clinical Research Center, India, Mumbai.

Duration: 14 days

Test product: VITROBIO Filmogen Glycerol Throat spray; Comparator/Control products: standard treatments

Number of patients: VITROBIO Throat Spray: 60 (36M + 24F); Control: 43 (19M + 24F)

Parameters evaluated: Effects on Throat Pain, Throat Irritation and Throat Inflammation; Bacterial count on throat surface (Throat swabs); Need for Antibiotherapy.

Results:

Need for Antibiotherapy

Group

Before treatment Day 1 Day 2 Day 7 Day 10 Day 14
VB-Throat Spray (n)

% population

60 0 2

3.33

3

5.0

4

6.66%

1

1.66%

Control group  (n)

% population

43 2

4.65%

13

30.23

14

32.56

8

18.60%

7

16.28%

Formula 1: Independent Observational Study (2015-2016)

 

Conducted by the Turkish Otorhinolaryngology Association
Number of patients: 4572
Design: multicentric clinical observational study
Note: Neither Vitrobio nor the Turkish distributor requested, sponsored, financed or was aware of this study being conducted.

The Turkish ENT Association wanted to verify new hypothesis. The following results were published in Turkey:

Before treatment (n) Treatment Day 3 (n) Treatment Day 7 (n)
Sore Throat 4185 1871 403
Cough 3831 1959 348
Irritation 4049 1549 422

 

Formula 2: Clinical Study

 

Study Design: A 14-day comparative, randomized, placebo controlled (parallel group), double blind, efficacy and safety study, according to ICH-GCP & MedDev guidelines.

Study Title:“A comparative, randomized, double-blind, parallel group, observational clinical trial study to evaluate efficacy and safety of throat spray containing VB-Gy (filmogen glycerol) and Septicyanidin premix versus Saline spray as Comparator in the treatment of patients with sore throat.”

CRO: NEXUS Clinical Research LLC USA, Ithaca NY & Subsidiary NEXUS Clinical Research Center, India, Mumbai.

Number of patients: VITROBIO Throat Spray: 36; Control: 18

Test product: VITROBIO Filmogen Glycerol Throat spray; Comparator/Control product: Saline solution

Products were applied as spray, every 20 to 30 min. during the first 2-3 hours then 3-4 times daily, for a maximum 14 days, and primary and secondary sore throat infection-related parameters were evaluated on days 1, 2, 3, 4, 7, and 14.

Parameters studied: Effects on Throat Pain severity, Throat Irritation, Swollen Throat, Swallowing Difficulty, Throat Redness (clinical sign of Inflammation), Whitish (bacterial) Deposits; Need for Antibiotherapy.

Results:

Findings

Saline solution showed some beneficial effects on sore throat, but the TP proved significantly more effective, producing not only very rapid but also durable effects on all clinical signs of pharyngitis. The statistically significant effectiveness and rapidity of results obtained with the test product, led to faster recovery and reduced need for antibiotics compared to the CP group. No treatment-related undesirable or adverse effect was observed.

Conclusions

This novel hypertonic, highly osmotic, filmogen liquid bandage is a safe and effective treatment for pharyngitis.

 

Advantages over competition:

VITROBIO throat sprays represent a totally new generation of sore throat treatment which is replacing all existing treatments in most of the countries where it is launched recently by known pharma companies like URGO, BMS-UPSA (France), Bouchara Recordati (Italy), Siemens-Sidroga (Germany), Walmark (Poland), Wockhardt (SE Asia).

Patented worldwide: Glycerol PCT/FR99/01340; Filmogen Glycerol: PCT/EP2013/061835; Antiviral polymers: WO2011/082835 A1. For further details please contact VITROBIO France.

VITROBIO‘s Completely NEW therapeutic Approach: Protein Hypothesis as Topical Anti-Virals.
As virus GPs & proteases are proteins in nature and as certain plant tannin fractions (PCDs) have a strong affinity for proteins, Vitrobio conducted 15 years of research to identify specific PCDs capable of binding with these protein structures. Blocking virus attachment & virus entry-enhancing mechanisms should stop virus infection (Ref: Vitrobio new anti-viral hypothesis – Shrivastava et al: Int. J. Virology, ISSN 1816-4900 / DOI: 10.3923/ijv.2011).
These PCDs were incorporated into a glycerol-based viscous liquid, 18 times more osmotically active than sea water yet NONIRRITANT (International patent 1997: PCT/FR99/01340). A new patent on the film retention properties of this solution was recently filed (N° PCT/EP2013/061835). PHARYSOL instantly forms a film on the throat surface, creates a strong outward flow of
hypotonic liquid detaching instantly all the microbial & other contaminants from the surface. Simultaneously, specific PCDs conjugate with viral GPs & proteases to stop further infection, reducing the need for antibiotherapy.
PHARYSOL acts as an instant topical anti-viral, antiseptic, preventive or curative, throat-cleaning film.

Product Presentation: 30 or 20mL Sprays
Posology: 4-5 sprays per application, 3-4 times a day or more if necessary, until complete recovery.
Regulatory Status: Due to the mechanical topical filmogen activity without any pharmacological, biological, metabolic or immunological interaction with the cellular structure: Class I Medical Device in Europe.
Contraindications: Not to be used in pediatric population under 3 years of age.
Side Effects: Slight tingling sensation during the first 20-30 seconds following application.
Clinical Efficacy: Full trial published in J. Clinical Trials, 2011, 1:1; DOI: 10.4172/jctr.1000102.

Conclusion: 1st topical Anti-Viral Instant Preventive or Curative
Spray to treat Viral Throat Infections