HK1141980B - Use of carrageenan for treating rhinovirus infections - Google Patents

Description

Application of carrageenan for treating rhinovirus infection

Technical Field

The present invention is in the field of immunological and antiviral agents and relates to pharmaceutical compositions comprising carrageenan as an active antiviral ingredient and their use in the prophylactic or therapeutic treatment of rhinovirus infections.

Background

Picornaviruses represent a very large viral family of small rna-containing viruses responsible for a variety of serious human and animal diseases. Picornaviruses comprise four major groups: enteroviruses, rhinoviruses, cardioviruses and aphtha viruses.

Human rhinoviruses consist of at least 100 serotypes and are the main causative agent of the common cold. Due to the large number of serotypes, vaccine development becomes a difficult problem; antiviral agents may therefore be the best therapeutic approach. Rhinoviruses are composed of an outer capsid comprising the four viral proteins VP1, VP2, VP3 and VP 4. The proteins VP1, VP2 and VP3 are organized into 60 repetitive pro-rotational isomeric icosahedral units (prokaryotic icosahedral units). These are believed to be responsible for the antigenic diversity associated with the virus.

Rhinovirus (HRV) infection causes the common cold, with symptoms such as fever, cough, and nasal congestion. HRV infection is the second most common vehicle associated with pneumonia and bronchiolitis in infants and young children, and often leads to exacerbation of an already existing respiratory disease in people with asthma, chronic obstructive pulmonary disease, or cystic fibrosis. HRV infection is associated with one-third to one-half exacerbation of asthma by age, and is associated with asthma hospitalization in both adults and children.

Existing therapeutic approaches include the use of rhinovirus-specific RNA, as disclosed in DE 19825395, which can bind to the capsid canyon region (canyon region) that is required for host receptor (e.g. ICAM-1, intercellular adhesion molecule-1) binding and cell infection.

Another method comprises administering soluble ICAM-1 protein or a derivative of ICAM-1 (tlCAM-1, truncated ICAM-1) as disclosed in US 6,326,004 and US 6,096,862 to neutralize viral particles (virions).

EP 0523803 discloses compounds having antiviral activity against rhinoviruses.

The symptoms of rhinovirus are caused by an excessive or nonspecific reaction of the immune system. Thus common treatment forms for rhinovirus infections include the administration of analgesics such as aspirin or acetaminophen (acetophene)/paracetamol (paracetamol) and localized forms to the throat (usually delivered in the form of lozenges), nasal decongestants to reduce inflammation of nasal passages by local vasoconstriction, antitussives which act to suppress the cough reflex of the brain or by diluting the mucus in the lungs, and first generation antihistamines such as brompheniramine, clotrimiprone and cromaline which reduce mucus gland secretions, thereby combating blocked/runny noses, but also making the user drowsy.

Sulfated polysaccharides, including carrageenan, are known in the art for their antiviral efficacy. In one of the most interesting reviews, Gonzalez M.E. et al (1987, Antimicrob. Agents Chemother.31, 1388-. Iota-carrageenan shows antiviral activity against enveloped viruses HSV-1, HSV-2, Semliki Forest Virus (SFV), vaccinia virus and African swine fever virus (ASF), and against naked-brain myocarditis (EMC) virus. Iota-carrageenan is ineffective against enveloped virus Vesicular Stomatitis Virus (VSV) and measles virus as well as against naked virus type 1 poliovirus and type 5 adenovirus.

US 2003/181415 a discloses the antiviral activity of sulfated polysaccharides such as cellulose sulfate against various enveloped viruses, especially Herpes Simplex Virus (HSV), papilloma virus and HIV.

WO 2005/004882a discloses the therapeutic treatment of viral infections other than rhinovirus infections with sulfated polysaccharides such as carrageenan.

US 2005/171053a1 discloses the use of lambda-carrageenan to inhibit the spread of sexually transmitted infections, including HIV-1 infections.

Yamada et al (1997, Carbohydrate Polymers, appl.Scien.publishers 32, 51-55) disclose anti-HIV-1 activity of lambda, kappa and iota carrageenans and their sulfated derivatives.

Tischer et al (2006, Carbohydrate Polymers, appl. Scien. publishers 63, 459-.

Carlucci et al (2004, Antiviral Research, Elsevier Science BV.64, 137-.

Pujol et al (2006, Planta Medica 72, 121-.

The term "carrageenan" is a commonly used collective term for polysaccharides extracted from linear sulfated galactans of seaweed (red algae). It is commonly used as a thickener, gelling agent, stabilizer or emulsifier in pharmaceutical and food products. There are more than 10 different carrageenans depending on the species of seaweed from which they are extracted. The three main types are iota-, kappa-and lambda-carrageenan, which differ slightly in structure and degree of sulfation. Iota-carrageenan is a soft gel-forming sulfated galactan extracted mainly from the red seaweed, Gigartina astrata (Gigartina tenella) and Chondrus crispus (Chondrus crispus). Kappa-carrageenan forms a strong, firm gel and is produced mainly from the alga Caliper barbata (kappaphycustotonii). Lambda-carrageenan, which is the most common form, is commonly used to thicken dairy products.

Although the antiviral activity of some carrageenans against viruses such as HIV or HSV has long been known, the mechanism of how carrageenans exert antiviral activity still needs to be clarified.

Based on the foregoing, the present invention now provides an antiviral composition of the carrageenan type suitable for prophylactic or therapeutic treatment of rhinovirus infections (rhinitis).

Experiments leading to the present invention have surprisingly demonstrated that despite the possible retention in the prior art, the selected carrageenans exert antiviral activity against rhinovirus infections (rhinitis), with iota-carrageenan yielding the best results.

Disclosure of Invention

Thus, the present invention relates in a first embodiment to the use of carrageenan as an active antiviral ingredient in the manufacture of a pharmaceutical composition for the prophylactic or therapeutic treatment of rhinovirus infections.

The term "active antiviral ingredient" as used herein refers to a carrageenan compound which, when applied in an effective dose or amount, can directly and/or indirectly interfere with the rhinovirus infectious cycle of eukaryotic cells, more specifically with at least a portion of a rhinovirus infectious cycle selected from the group consisting of virus entry into eukaryotic cells, virus replication in eukaryotic cells, virus assembly, and virus release from infected eukaryotic cells. It also includes any effect that non-specifically inhibits the increase of viral titer or non-specifically reduces the level of viral titer in a eukaryotic or mammalian host system. The term also refers to compounds that have prophylactic efficacy such that they can, at least to some extent, protect against or reduce the likelihood of becoming sick from a viral infection.

The present pharmaceutical composition may thus be administered before or after the onset of the viral infection. The term "prevention" or "prophylactic treatment" as used herein relates to the administration of the present pharmaceutical composition so as to at least to some extent prevent or reduce the risk of falling ill from a viral infection.

The terms "treatment" or "therapeutic treatment" as used herein relate to the administration of the present pharmaceutical composition to an individual already infected with a virus so as to reduce the pathological effects of said infection, including reducing the severity and/or frequency of the symptoms presented, or eliminating said symptoms, treating possible damage caused by or associated with said viral infection, and including the inhibition or prevention of secondary viral, bacterial, fungal or any other type of microbial infection.

The collective term "carrageenan" as used hereinafter refers to mixtures of at least two of iota-carrageenan, kappa-carrageenan and lambda-carrageenan homopolymers or heteropolymers, i.e., refers to mixtures of iota-carrageenan and lambda-carrageenan, mixtures of iota-carrageenan and kappa-carrageenan, mixtures of kappa-carrageenan and lambda-carrageenan, or mixtures of iota-carrageenan, kappa-carrageenan and lambda-carrageenan homopolymers or heteropolymers, unless explicitly stated otherwise or unless a different meaning can be deduced from the essence of the relevant disclosure.

The carrageenan homopolymer is a molecular pure carrageenan compound of any one of iota carrageenan, kappa carrageenan or lambda carrageenan. The carrageenan heteropolymer comprises subunits of at least two different types of carrageenan, preferably selected from the group consisting of iota-, kappa-and lambda-carrageenan subunits.

The term "mixture" of carrageenans, if referred to hereinafter, may also refer to a composition of matter comprising at least one heteropolymer of carrageenans as the active antiviral ingredient, whereby the "mixture" is predominantly a mixture of different carrageenan subunits as part of the at least one heteropolymeric carrageenans present in the composition.

In another embodiment the invention relates to such an anti-rhinovirus composition for prophylactic or therapeutic use, wherein the rhinovirus infection is an acute or chronic rhinovirus infection.

The carrageenan-based compositions are suitable for topical application to treat skin or mucosal inflammation. But may also be used systemically such as parenterally or orally, especially when engineered to contain predominantly low molecular weight carrageenan fractions. The carrageenan useful in the present invention has an average molecular weight of about 15000Da to 5000000 Da. The low molecular weight portion comprises carrageenan having an average molecular weight of about 15000Da to about 50000Da, the medium molecular weight portion comprises carrageenan having an average molecular weight of about 50000Da to about 500000Da, and the high molecular weight portion comprises carrageenan having an average molecular weight of about 500000Da to about 5000000 Da.

In a preferred embodiment, the pharmaceutical composition is suitable for topical or mucosal application. Suitable galenic forms of ready-to-use formulations are creams, gels, ointments, powders (including powders for inhalation), sprays, foams or liquid solutions such as skin lotions, gargles or nasal drops. Other suitable forms of galenic formulations will be apparent to those of ordinary skill in the art, including nasal drug delivery systems such as disclosed in US 6,391,452.

In addition to the active antiviral ingredient, the present compositions will generally comprise at least one pharmaceutically acceptable carrier and, if desired, other additives or ingredients.

Suitable carriers may be diluents such as water or saline, excipients or additional carriers suitable for administration of the active ingredient. The optional additives may be selected from the group consisting of: SiO 2₂，TiO₂Binders, such as microcrystalline cellulose, polyvinylpyrrolidone, tragacanth, gelatin, starch, lactose monohydrate, alginic acid or corn; lubricants or surfactants, such as magnesium stearate or sodium lauryl sulfate; glidants, such as colloidal silicon dioxide; sweetening agents, such as sucrose or saccharin. Other additives in the formulation may be, but are not limited to, buffers or pH adjusting agents, for example selected from citric acid, acetic acid, fumaric acid, hydrochloric acid, malic acid, nitric acid, phosphoric acid, propionic acid, sulfuric acid, tartaric acid or combinations thereof.

Other ingredients may also be present, including non-carrageenan drugs or pharmaceutically active substances.

The carrageenan may be used in the form of any pharmaceutically acceptable salt, for example the sodium salt of carrageenan may be used. In addition, other pharmaceutically acceptable salts include potassium, lithium and ammonium salts of carrageenan.

In another embodiment the composition of the invention is topically applicable and the amount of carrageenan present is from 0.01% to 20%, preferably from 0.1% to 10%, most preferably from 0.5% to 5% by weight of the formulation.

Typically, the composition may be provided as a non-pyrogenic (non-pyro) sterile formulation. For liquid formulations, sterility can be achieved, for example, by filtration through a suitable membrane filter. Methods of manufacturing sterile or aseptic pharmaceutical compositions are well known in the art and are not part of the present invention.

However, it is also possible to apply the pharmaceutical composition of the invention on solid surfaces of hygiene or cleaning articles, such as facial hygiene or cleaning articles commonly used in the oral and/or nasal area, such as nasal tissues (tissue) or papers and handkerchiefs. More specifically, the pharmaceutical composition may be applied (e.g., sprayed, much like a disinfectant) onto gloves, hygiene tissues or papers, including nasal tissues, to exert a virucidal effect, at least to some extent, thereby helping to reduce repeated self-infection of individuals through contaminated fingertips and also helping to reduce viral transmission between different individuals in close (e.g., hand-to-hand) contact with each other. Depending on the nature of the hygiene or cleaning article, the article may be coated, wetted or impregnated with the pharmaceutical composition.

The carrageenan-treated article may also include, but is not limited to, a cotton swab, a dust mask, or a face mask. Even lipsticks may be formulated containing an antiviral effective amount of carrageenan. These sanitary or cleansing articles may be used prophylactically or in conjunction with a therapeutic treatment to combat viral infections and may assist in avoiding or reducing the risk of infection.

Thus, in one embodiment, the invention relates to the use wherein the antiviral composition is applied by coating or impregnation to a solid surface of a hygiene or cleaning article, in particular a hygiene or cleaning glove, tissue or paper, especially nasal tissue or paper.

Iota-, kappa-and lambda-carrageenans useful in the present invention are commercially available or can be prepared by extraction from seaweed plants according to extraction procedures known in the art.

In a preferred embodiment of the present invention, the present invention relates to the use of at least one substance selected from the group consisting of homo-and heteropolymers of iota-, kappa-and lambda-carrageenans.

In a particular embodiment, the antiviral pharmaceutical composition of the present invention is substantially free of carrageenan forms other than iota-, kappa-and lambda-carrageenan, although trace amounts of such other carrageenans may be present. For various applications iota-carrageenan may be essentially the only carrageenan present in the composition.

In another embodiment, the present invention relates to the use of carrageenan in the manufacture of an antiviral composition, wherein the composition comprises iota-, kappa-or lambda-carrageenan, or a mixture of at least two of said carrageenans, in an amount of greater than or equal to 80 wt%, greater than or equal to 90 wt%, greater than or equal to 95 wt%, or even greater than or equal to 99 wt% of all carrageenan present in the composition. The percentages given are weight percentages (% w/w) relative to the dry weight of the carrageenan referred to.

In another embodiment, the present invention relates to a use wherein the composition comprises greater than or equal to 50 wt%, greater than or equal to 70 wt%, greater than or equal to 80 wt%, and preferably greater than or equal to 95 wt% iota-carrageenan on a dry weight basis relative to the total dry weight of all carrageenan present in the composition.

The carrageenan concentration values described above are equally applicable to homo-and heteropolymeric carrageenans.

Carrageenan has not been found to be toxic even when applied at very high doses for oral or dermal administration, or inhalation, and is therefore classified as "generally recognized as safe" (GRAS) by the Food and Drug Administration (FDA).

In another embodiment, the present invention relates to the use of carrageenan in the manufacture of an antiviral composition, said composition further comprising at least one other pharmaceutically active antiviral compound, preferably cellulose sulfate.

In another embodiment, the present invention relates to the use of carrageenan, preferably iota-carrageenan, for the manufacture of a pharmaceutical composition for the prophylactic or therapeutic treatment of a body condition selected from the group consisting of a microbial infection, an inflammatory disease, an allergy and an impaired or suppressed immune system, wherein the carrageenan is present in combination with at least one other pharmaceutically active compound or a drug. In such compositions, the carrageenan may function as an anti-rhinovirus adjuvant. The at least one further pharmaceutically active compound or drug may be selected from the group consisting of steroids (such as cortisone) and antihistamines.

In another embodiment, the antiviral pharmaceutical formulation is for use in the treatment or prophylaxis of an individual particularly susceptible to or at increased risk of a rhinovirus infection, such as a high risk patient selected from the group consisting of asthmatic patients, people with allergy and people with inflammatory disease.

Drawings

Figure 1 shows the results of the HRV-induced inhibition of cell death assay (XTT assay).

ordinate-OD (optical density) measured at 492 nm; the abscissa is the different test samples; 1 ═ uninfected cells; 2 ═ untreated infected cells; 3 ═ iota-carrageenan treated infected cells; 4 ═ kappa-carrageenan-treated infected cells; 5 ═ lambda carrageenan-treated infected cells; figure 1A ═ HRV-2 infected cells; figure 1B-cells infected with HRV-14.

FIG. 2 shows passing TCID₅₀Assays performed to determine peak titers of supernatants of infected HeLa cells were tested.

Ordinate is TCID₅₀The titer; iota-carrageenan concentration in μ g/ml on the abscissa; u ═ untreated cells; t (treatment) — cells were infected for 1 hour and iota-carrageenan was added at the indicated concentrations 1 hour after treatment; p (prevention) — the viral suspension was preincubated with iota-carrageenan at the indicated concentrations for 1 hour prior to infection. Other processing is the same as T: cells were infected at a multiplicity of infection of 0.01. Peak titers of HRV-2 were observed on day 3 (FIG. 2A) and HRV-14 on day 4 (FIG. 2B).

FIG. 3 shows passing TCID₅₀Testing of iota-carrageenan on infected human nasal epithelial cellsThe inhibition of rhinovirus replication.

ordinate-TCID expressed as logarithm (log)₅₀The titer; iota-carrageenan concentration in μ g/ml on the abscissa; MOCK ═ untreated control cells; figure 3A ═ cells infected with HRV-1A; figure 3B-HRV-2 infected cells; figure 3C ═ cells infected with HRV-8; figure 3D ═ cells infected with HRV-16; figure 3E ═ cells infected with HRV-39; figure 3F ═ cells infected with HRV-83.

Figure 4 shows the efficacy of iota-carrageenan against rhinovirus after repeated treatments as determined by the CPE inhibition test.

CPE inhibition in% on the ordinate; iota-carrageenan concentration in μ g/ml on the abscissa; HRV2P0 strain (original rhinovirus strain) (no replication cycle); HRV2P10 strain-rhinovirus HRV2P0 strain after 10 selective replication cycles on HeLa cells.

Detailed Description

In order that the invention described herein may be more fully understood, the following examples are set forth. The examples are for illustrative purposes only and should not be construed as limiting the invention in any way. It is also to be understood that the invention is intended to cover such departures from the present disclosure as come within known or customary practice in the art to which this invention pertains.

Example 1: anti-human rhinovirus type 2 (HRV-2) and human rhinovirus type 14 (HRV-14) effects of different types of carrageenans

The viral suspension was preincubated with 125. mu.g/ml of the polymer shown in FIG. 1 for 5 minutes, and the near confluent HeLa cells were incubated with the viral suspension. Cell viability was determined after 48 hours by the TOX2 XTT test (Sigma).

As shown in figure 1, the most effective polymer was found to be iota-carrageenan (column 3), which was effective against 2 types of rhinovirus, while lambda-carrageenan (column 5) and kappa-carrageenan (column 4) showed efficacy against HRV-2, but not against HRV-14. Error bars indicate standard deviation between 6 individual wells.

Example 2

The polymers shown in Table 1 were tested in HRV-2 and HRV-14 induced inhibition of cell death assays (XTT-assay) at a concentration of 100. mu.g/ml.

As shown in table 1, iota-carrageenan produced protection against both types of rhinovirus ("+" indicates at least 95% protection compared to uninfected control cells). Kappa-carrageenan and lambda-carrageenan have activity against HRV-2 but not against HRV-14. The polymers chitin, carboxymethyl cellulose and carboxymethyl chitin do not show inhibitory effects at all.

Table 1: antiviral Activity of several polymers tested

Polymer and method of making same	HRV-2	HRV-14
			Iota-carrageenan	+	+
Kappa-carrageenan	+	-
			Lambda-carrageenan	+	-
Chitin	-	-
			Carboxymethyl cellulose	-	-
Carboxymethyl chitin	-	-

Example 3

Iota-carrageenan is effective against HRV-2 and HRV-14 in models for treatment and prevention of viral replication. Significant reductions in peak viral titers were observed at concentrations greater than and equal to 6.25 μ g/ml. Iota-carrageenan, however, was most effective against HRV-2 in a prophylactic model, where a peak viral titer reduction of over 99.9% was observed.

Example 4: effect of iota-carrageenan against selected human rhinovirus subtypes

Near confluent HeLa cells in 96-well plates were incubated with a viral suspension with an MOI (multiplicity of infection) of 0.5.

20 minutes after infection with the virus suspension, nutrient medium containing 3-fold dilution of the polymer was added. Cell viability was determined by the TOX2 XTT assay (Sigma) after 48-72 hours. EC was calculated with software Excel-Fit₅₀The value is obtained.

TABLE 2

Virus

HRV-1

HRV-2

HRV-8

HRV-14

HRV-16

HRV-39

EC50

0.7μg/ml

21μg/ml

＜0.5μg/ml

400μg/ml

381μg/ml

117μg/ml

Iota-carrageenan has activity against all tested human rhinoviruses on pre-infected HeLa cells. The concentration of carrageenan required to inhibit 50% of the cytopathic effect varied over a wide range, being < 0.5. mu.g/ml for HRV-8 and 400. mu.g/ml for HRV-14. This result indicates that iota-carrageenan inhibits the replication of a broad spectrum of rhinovirus subtypes on infected HeLa cells.

Example 5: inhibition of rhinovirus replication on human nasal epithelial cells by iota-carrageenan

Will be originalHuman nasal epithelial cells (Promocell) were seeded in 24-well plates (2.9X 10)⁴Cells/well) and 5% CO at 37 ℃₂And 95% humidity for 3 days. Cells were infected with the rhinovirus strains HRV-1A, HRV-2, HRV-8, HRV-14, HRV-16, HRV-39, HRV-83 and HRV-84 at approximately 60% confluence. Rhinoviruses HRV-1A, HRV-2, HRV-8, HRV-16, HRV-39 and HRV-83 undergo lytic replication on human nasal epithelial cells. HRV-14 and HRV-84 did not lyse cells and were not tested further. The virus was pre-incubated with iota-carrageenan at concentrations of 4. mu.g/ml, 40. mu.g/ml and 400. mu.g/ml and a MOCK control. The MOI was 0.34. Supernatants were harvested 48-72 hours post infection and used for TCID₅₀And (4) measuring the titer. As shown in figure 3, treatment with iota-carrageenan reduced the viral titer of all viruses in the supernatant by at least 2 log (> 99%) (the Y-axis shows the viral titer expressed as log) at a concentration of 40 μ g/ml compared to MOCK-treated control cells. These data clearly show that iota-carrageenan inhibits viral replication on primary human epithelial cells. Since it appears that there is currently no animal model available for in vivo testing of human rhinoviruses, the human nasal epithelial cells used in the present invention represent the most important in vitro model currently available. Error bars represent standard deviations between 3 independent test samples.

Example 6: determination of the efficacy of iota-carrageenan against rhinovirus infection after repeated treatments (examination of the possibility of development of viral resistance)

Original virus HRV2P0 and virus HRV2P10 obtained after 10 selective replication cycles on HeLa cells were tested in CPE (cytopathic effect) inhibition assay. HeLa cells (8X 10)⁴Individual cells/well) were seeded in 6-well plates. The cells were infected with a suitable nutrient medium supplemented with carrageenan polymer and at final concentrations of carrageenan of 1.6. mu.g/ml, 5.3. mu.g/ml, 17. mu.g/ml, 50. mu.g/ml, 150. mu.g/ml and 450. mu.g/ml and further containing a virus with an MOI of 0.1.

As a control, one well was MOCK infected with virus-free and carrageenan-supplemented nutrient medium, and the other well was infected with virus suspension treated MOCK, i.e. a virus suspension containing nutrient medium but no carrageenan. After an incubation time of 20 minutes following infection, the plates were washed twice and control medium (no virus and supplemented with carrageenan at the selected concentration) was added to all wells except the MOCK-treated negative control (i.e. uninhibited, complete infection). Samples were taken from each experimental well as soon as a significant cytopathic effect was seen in the unprotected negative control well. For the subsequent selection cycle, virus-containing supernatant samples were taken from those carrageenan-treated wells that showed a clearly detectable CPE compared to the uninfected control and used to infect HeLa cells. Typically, CPE responses were detectable in only the two experimental samples with the lowest carrageenan concentrations (i.e., 1.6 μ g and 5.3 μ g carrageenan per ml).

This procedure was repeated 10 times and the virus samples obtained were compared to the original virus strain in the CPE inhibition test. Briefly, TOX2 reagent (Sigma) was added 48 hours after infection and OD was measured_450nmValues and CPE inhibition expressed as% uninfected control were determined.

To examine the possibility of viral resistance to carrageenan treatment, the virus used for the first inoculation (virus 2_001 in fig. 4) and the virus obtained after 10 selective replication cycles (virus 20_001 in fig. 4) were tested in a CPE inhibition assay using HeLa cells according to an experimental protocol slightly different from that described above. Briefly, HeLa cells were infected with each virus at an MOI of 0.1, the inoculum was removed 20 minutes after infection, and nutrient media containing carrageenan polymers at final concentrations of 1.6. mu.g/ml, 5.3. mu.g/ml, 17. mu.g/ml, 50. mu.g/ml, 150. mu.g/ml and 450. mu.g/ml were added (see abscissa of FIG. 4). TOX2 reagent (Sigma) was added 48 hours after infection and OD was measured_450nmValues and determination of CPE inhibition expressed as% uninfected control (figure 4, ordinate). Error bars indicate standard deviation between 6 individual wells.

As illustrated in fig. 4, no significant difference in the sensitivity of the virus to carrageenan treatment was detected in the samples obtained from the supernatants of infection cycle 1 and 10. This indicates that no escape mutation (escape mutant) occurred during the selection procedure. These data therefore indicate that even with prolonged continuous or repeated treatment, there is no possibility of rhinovirus escape during in vivo treatment with iota-carrageenan.

Claims (21)

1. Use of iota-carrageenan as an active antiviral ingredient in the manufacture of a pharmaceutical composition for the prophylactic or therapeutic treatment of a rhinovirus infection.

2. The use of claim 1, wherein the rhinovirus infection is an acute or chronic rhinovirus infection.

3. Use according to claim 1 or 2, wherein the composition is suitable for topical or mucosal application.

4. The use of claim 3, wherein the composition is suitable for use as a nasal spray, powder, gel, ointment, foam, or liquid solution.

5. Use according to claim 3, wherein the composition is suitable for use as a powder for inhalation, a lotion, a mouthwash or drops.

6. Use according to claim 1 or 2, wherein the composition further comprises at least one pharmaceutically acceptable carrier or additive.

7. Use according to claim 1 or 2, wherein the composition is suitable for topical application and comprises iota-carrageenan in an amount of 0.01% to 20% (w/v) of the formulation.

8. Use according to claim 7, wherein the composition comprises iota-carrageenan in an amount of from 0.1% to 10% (w/v) of the formulation.

9. Use according to claim 7, wherein the composition comprises iota-carrageenan in an amount of from 0.5% to 5% (w/v) of the formulation.

10. Use according to claim 1 or 2 wherein the composition further comprises at least one additional carrageenan selected from the group consisting of kappa-carrageenan and lambda-carrageenan.

11. Use according to claim 1 or 2, wherein the composition comprises iota-carrageenan in an amount of greater than or equal to 50% by weight relative to the sum of all carrageenan present in the composition.

12. Use according to claim 11, wherein the composition comprises iota-carrageenan in an amount of greater than or equal to 80 wt% relative to the sum of all carrageenan present in the composition.

13. Use according to claim 11, wherein the composition comprises greater than or equal to 95% by weight iota-carrageenan relative to the sum of all carrageenan present in the composition.

14. Use as claimed in claim 1 or 2, wherein the composition further comprises at least one other pharmaceutically active antiviral ingredient.

15. Use according to claim 1 or 2, wherein the composition is applied to a solid surface of a hygiene or cleaning article.

16. The use of claim 15, wherein the composition is coated on a solid surface of a nasal tissue.

17. Use according to claim 1 or 2, wherein the composition further comprises at least one other pharmaceutically active compound selected from steroids and antihistamines.

18. Use according to claim 1 or 2, wherein the rhinovirus infection is present in an individual being a high risk patient selected from the group consisting of asthmatic patients, people with allergy and people with inflammatory diseases.

19. A solid hygiene or sanitary article coated or impregnated with the antiviral composition of any one of claims 1 to 18.

20. The solid hygiene or cleaning article of claim 19, said article being selected from the group consisting of gloves, hygiene tissues, facial hygiene articles for the mouth and/or nose region and facial cleaning articles.

21. The solid hygiene or cleaning article of claim 20, which is a nasal tissue.