WO2019209227A2

WO2019209227A2 - Solid oral formulations comprising herbal extracts

Info

Publication number: WO2019209227A2
Application number: PCT/TR2018/050920
Authority: WO
Inventors: Ali TÜRKYILMAZ; Gülay Yelken; Mustafa MARASLI
Original assignee: Montero Gida Sanayi Ve Ticaret AS
Current assignee: Montero Gida Sanayi Ve Ticaret AS
Priority date: 2017-12-29
Filing date: 2018-12-27
Publication date: 2019-10-31
Anticipated expiration: 2020-06-29
Also published as: WO2019209227A3; WO2019209229A2; WO2019209229A3; WO2019199260A2; TR201809956A2; WO2019199260A3; TR201722959A2; TR201804828A2

Abstract

The present invention relates to an herbal formulation comprising propolis extract and berberis vulgaris extract for providing treatment in various respiratory diseases such as cold, cough, allergic asthma, seasonal allergic rhinitis, bronchitis, pharyngitis, laryngitis and pneumonitis.

Description

SOLID ORAL FORMULATIONS COMPRISING HERBAL EXTRACTS

Technical Field

Background of the Invention

In recent years, the use of various herbs and/or herbal medical products for the prevention and treatment of diseases and alleviating the effects thereof have been gradually increasing in all societies. Throughout the human history, there have been and still are attempts for treating many diseases (diabetes, jaundice, dyspnea, etc.) by using some herbs. According to the records of the World Health Organization (WHO), a large proportion of the world's population (70-80%) make use of herbs for therapeutic or prophylactic purposes. Additionally, around 25% of prescription drugs in developed countries are composed of plant-based active agents (vinblastine, reserpine, quinine, aspirin, etc.).

Particularly following the end of the 1990s, the discovery of new areas of use for medical and aromatic herbs and the increasing demand for natural products have increased the use potential thereof day by day.

Herbal medical products have long been in use for the treatment or prophylaxis of respiratory diseases. In the treatment or prophylaxis of these diseases which are typically caused by viruses, bacteria, and/or fungi, it is quite significant both to eradicate these harmful organisms and to boost the immune system of the affected individual. This is because the immune system is comprised of processes providing protection against diseases, as well as recognizing and eliminating the pathogenic and tumor cells in a living being. The system scans the organism against any kind of foreign substances, entering or contacting the former, from viruses to parasitic worms of a wide variety, and distinguishes them from the organism's own healthy cells and tissues. The immune system can even distinguish substances with very similar features from each other to such an extent that even proteins having a different amino acid can be distinguished from the equivalents thereof. The function of the immune system is primarily to prevent harmful foreign substances from entering the respective organism, or upon entry, to retain the substances at the place of entry, or to prevent or delay their spreading therein.

Berberis vulgaris berries are edible and rich in vitamin C. Berberine is the main active alkaloid with a benzyl tetra hydroxy quinoline chemical structure which can be found in all part of berberis vulgaris especially in its fruit (barberry). It is odorless but with a bitter taste powder which is sparingly soluble in methanol, slightly soluble in ethanol and very slightly soluble in water.

Propolis is one of the most important bee products. Besides its antibacterial, antifungal, antiviral features, a great number of beneficial biological activities such as anti inflammatory, anti-ulcer, local anesthetic, anti-tumor and immunity stimulant properties popularizes its usage in medicine, apitherapy, health nutrition and biocosmetic fields. It comprises 150 chemical compounds, more than 20 mineral substances, beeswax, resin and pollen. In chemical terms, propolis comprises a wide variety of extremely complex and potent terpenes, benzoic acids, caffeic acids, cinnamic acids, and phenolic acids. It has a high flavonoid content.

Propolis is one of the most powerful antibiotics found in nature. It is rich in terms of amino acids and trace metals, has a very high vitamin content and contains at least 38 valuable bioflavonoids. It is an invaluable antioxidant based on its high bioflavonoid content. It was demonstrated to inactivate at least 21 bacteria species, 9 fungi species, 3 protozoa (including giardia), and a wide spectrum of viruses.

In the studies, a lot of advantages of propolis for health are demonstrated. Some of these studies are: 1 ) A clinical study conducted in Spain in 1988 on 138 individuals has shown that the usage of a propolis based supplement is as effective as the usage of antiprotozoal drug tinidazole which is extensively used in the treatment of infections caused by giardiasis parasite. 2) A study published in Nutrition and Cancer in 2003 has shown that propolis has revitalized apoptosis and provided the tissue decomposition of the lung cancer tumors in mouse. 3) According to National Institutes of Health, propolis may be used as an effective anti-inflammatory agent against aphtha and other gingiva wounds and peptic ulcer. 4) Blue Shield Complementary and Alternative Health has reported that propolis is two times more effective than acyclovir which is the conventional anti-viral drug in herpes treatment. 5) According to a study published in American Journal of Biochemistry and Biotechnology on February 2004, propolis kills the human breast cancer cells called MCF-7. 13% of the cancer cells of the participants were killed only within 24 hours following the administration of propolis extract.

Pelargonium sidoides (African Geranium, Umckaloabo) is a plant species widely used in the treatment and prevention of, or in the alleviation and/or elimination of the symptoms of cold and respiratory tract disease (pharyngitis, sinusitis, acute bronchitis, tonsillitis). It was determined to be effective in increasing the generation of natural killer cells and tumor necrosis factor alpha, and to enhance the release of interferon beta. Pelargonium sidoides has antiviral properties strengthening the immune system. It further has both antibacterial effects and antioxidative properties against some bacteria. Apart from that, it was also reported to boost the immune system of the respective organism and to have expectorant action by increasing the ciliary beat frequency of respiratory epithelial cells. In a multicenter study conducted by the Pneumology Department of a German University Hospital (2000) on acute bronchitis patients, including adults, children, and infants, it was determined that an extract of the roots of Pelargonium sidoides reduced the severity of the symptoms after 7 days treatment from 6.3 to 0.9 according to the average bronchitis severity score. A study published in "Acta Paediatrica" in April 2010, showed that preparations extracted from herbal roots were much more effective in the treatment of acute bronchitis as compared to placebo. A study group of children aged 6 to 18 years, taking the herbal extracts experienced less coughing, sputum, and bed rest times versus placebo. By assessing the results of four placebo-controlled clinic trials, the researchers at the Medical Center, the University of Pittsburgh, concluded that a standardized extract of Pelargonium sidoides showed a much better performance in alleviating the bronchitis symptoms versus placebo in a 7-day treatment period.

Echinacea purpurea, the purple coneflower, is a plant species widely used in the prophylaxis and/or treatment of infection, cold, cough, bronchitis, flu, in the treatment of infection of the urinary system, in the treatment of the sore throat and toothache, in boosting the immune system, and externally, in the treatment of snakebite, eczema, psoriasis, acne, wounds and burns. Echinacea purpurea is known to have immunostimulant, anti-inflammatory, antibacterial, antiviral, antifungal, anticancer, cicatrizant activities. The compounds accounting for these activities are thought to be polysaccharides, glycoproteins, alkylamides, and caffeic acid derivatives (cichoric acid, echinacoside). Echinacea purpurea supports the production of interferon, thereby strengthening the defense system of the respective organism. Interferon activates the natural killer cells and induces these cells to bind to and destroy infected cells or tumor bearing cells. Interferon is effective in releasing the enzymes destroying the genetic structure of viruses and inhibiting their reproductive and spreading capabilities.

Ginseng root is harvested after a cultivation period of 6 years and this part of the plant is used for therapeutic purposes. It comprises saponins (dammaran and oleanan derivatives; ginsenosites), polyacetylene derivatives and polysaccharides. The effects of Ginseng on the body are not local, and thus, one of the benefits of Ginseng is that it strengthens the entire body and helps in balancing entire body systems. Ginseng is an antioxidant and an important immunity system improver which increases the number of immunity system cells in the body. It is useful in the treatment of bronchitis, asthma and the circulation problems. According to a study conducted by American scientists, the flu risk of people who are administered 200mg ginseng root capsules twice a day reduced by 31%. In the laboratory and animal experiments, it is found that it is effective against prostate, stomach, kidney, liver, large intestine, brain and lung cancers. In the animals with prostate cancer, it prevented the development of cancer.

Ginger (Zingiber officinale) is also called "warming herb" and used for a long time as an important medical herb. It comprises essential oils with ether comprising Zingiberene, Zingiberol, Gingerol and Shogol. The essential oils contained which are mixed with terpenoids give the special taste and scent of ginger. The bitter substances without essential oils which make the mouth feel warm are gingerol and zingeron.

Ginger has a wide area of usage. Ginger is preventive against cancer based on stopping the Epstein-barr virus activity. 6-gingerol and 6-paradol, among the active substances of ginger, are effective in stopping promyelocytic leucaemia by disturbing the DNA synthesis. It also has anti-inflammatory effect, is effective against arthritis and headache, and is bacteriostatic. It is used against nausea, spasm and fever in kids. Based on its antiseptic effect, it is used against stomach and intestine infections and even against food poisoning. It also prevents the coagulation of the blood and has blood thinning effect. It supports the cardiovascular system by making the platelets less adherent, this in turn causes a decrease in the problems of the circulation system. It is appetizing and can also be used against constipation. In addition to these, it has a warming and sedative effect in cough, flu, cold and other respiratory system diseases. Honey is the natural product processed by honeybees from flower nectars or plant secretions, by aid of their own secretions. Honey is a nutritious, sweet and healthy food, and minor components of honey include proteins (0.25-0.5%), organic acids, aminoacids, vitamins, flavonoids and water. The amount of water in honey is between 15.00% and 30.00% by weight.

Honey has been used for treatment of microbial infections since ancient times. In recent years there has been a resurgence of interest in the therapeutic efficacy of honey. While it may naturally have a long shelf life, heating and cooling the spread too many times can cause it to lose its colour and aroma. Shelf-life of honey depends on botanical origin as well as processing.

TR2014/02396B relates to process for producing solid honey which has water in an amount less than 1.00% by weight.

EP2387329B1 relates to a honey product comprising honey having a low moisture content.

Honey is an excellent source of easily digestible sugars. It is largely composed of glucose and fructose, monosaccharides that are rapidly absorbed and metabolized by the organism. It also contains volatile components which makes it a very palatable ingredient. Honey may contain enzymes, pollen and propolis which have been recognized as having excellent health benefits.

Products to be used for medical purposes have to incorporate the elements of quality, efficiency, and reliability. A product can be a "medical" product only by having these elements. In order for a product prepared from a herbal source to be a medical product, it has to be prepared from an efficient and standardized extract, to have established pharmacological, clinical outcomes and toxicological data, and a determined stability. Therefore, it bears great significance to have a good stability for a product, produced from herbal sources, to be used in the treatment and prevention of diseases, or in the alleviation and/or elimination of the symptoms thereof.

Physical, chemical, and microbiological factors play role in the stability of medicaments or other products prepared for medical purposes. The stability issue is not dependent on a simple cause only but emerges as a result of many factors. Factors such as the interaction of active agents contained in a product, the interaction of excipients among themselves or with active agents, pH, light, humidity, and temperature are among many elements which may influence the stability of such products.

Until recently, the researchers deemed considerable importance on the chemical stability of pharmaceutical products rather than the physical stability thereof and conducted many studies accordingly. In many instances, however, they could show how important the changes in the physical structures of products are for the product quality, and for the durability of the technologic, microbiologic, and biopharmaceutical properties thereof. Accordingly, it was shown that primarily the physical stability of a product has to be maintained in order to sustain its quality and other features thereof, and therefore ensuring the physical stability during the development of pharmaceutical products is as important as, or sometimes more important than ensuring the chemical stability thereof.

Additionally, the physical properties are taken into account in the evaluation of the physical stability of a product, particularly the taste, scent, color, clarity, uniformity, etc. of a product, also considerably influence the patient compliance. For this reason, when a novel formulation is developed, besides aiming a formulation of good physical stability, the physical properties of this formulation should be made ideal to provide high patient compliance.

However, it is quite difficult to provide the above described conditions in the formulations comprising herbal substances. Due to some characteristic chemical, biological and physical properties of the herbal substances used in the formulation, some problems are encountered in obtaining a formulation comprising said substances as well as having a good physical stability and ideal physical properties in terms of patient compliance.

The physical properties and the physical stability of a formulation are influenced directly from the characteristic properties of herbal agents contained therein. Some aspects of herbal agents contained in a formulation, such as having a bad taste, a bad scent, a bad color and similar physical properties, becoming easily oxidized, and providing a suitable medium for the reproduction of microorganisms negatively influence the physical properties and physical stability of that formulation. Additionally, in case a formulation comprises a combination of herbal agents, a correct selection of the herbal agents bears great importance, since more than one herbal agent present in the same formulation is capable to mutually affect their respective properties. Even if there are formulations comprising herbal extracts and honey in prior art, it would be desirable to provide a new formulation, as well as a process for the preparation of this formulation, comprising combinations of herbal agents, being capable to retain the physical stability for a long time, and having ideal physical properties in terms of patient compliance for the treatment of respiratory diseases.

In detail, there is a need in the state of art for a formulation comprising extracts of propolis and berberis vulgaris, and having ideal physical properties to ensure high patient compliance and good physical stability, as well as to a method for preparing this formulation, which is simple, cost-efficient and time-saving.

Object of the Invention

The main object of the present invention is to obtain formulations which have improved physical stability, comprising propolis extract and berberis vulgaris extract.

Another object of the present invention is to provide formulations with a significantly improved stability, as well as the excellent long-term stability.

Another object of the present invention is to provide formulations for providing treatment in various respiratory diseases such as cold, cough, allergic asthma, seasonal allergic rhinitis, bronchitis, pharyngitis, laryngitis and pneumonitis.

Another object of the present invention is to provide formulations which have increased quality, reliability, and shelf life as a result of an improved physical stability.

Another object of the present invention is to provide formulations comprising berberis vulgaris extract and propolis extract, which both maintains the physical stability and has improved physical properties as a result of using suitable excipients.

Yet another object of the present invention is to develop formulations which are capable of providing an easy administration accompanied by an increased patient compliance and convenience. A further object of the present invention is to provide a simple, cost-efficient, and time saving process for preparing formulations comprising berberis vulgaris extract and propolis extract.

Detailed Description of the Invention

In order to achieve the aforementioned objects, the present invention discloses a novel, stable, bioavailable, oral compositions for the oral administration of extracts of propolis and berberis vulgaris.

The maintenance of the physical stability of a pharmaceutical product can be ensured if no change occurs in the physical structure of that product. Therefore, whether the physical stability is maintained or not is assessed by determining changes in various physical properties of the product during formulation development process. Properties such as the color, scent, taste, pH, clarity, viscosity, homogeneity, density are among the physical properties of a pharmaceutical are the basic physical properties playing role in the assessment of the physical stability thereof.

Surprisingly, in the physical stability studies conducted during development of a herbal formulation comprising berberis vulgaris extract for medical purposes, it is found that in the event of adding another substance, propolis extract, into the formulation, physical stability of the product is improved. Furthermore, owing to therapeutic properties of propolis, the efficacy of the formulation increases.

A formulation according to the present invention, comprises propolis extract and berberis vulgaris extract.

In one embodiment, the formulation is administered by oral, parenteral, ocular, nasal, buccal, sublingual and topical route.

In one preferred embodiment, the formulation is administered by oral route.

In one embodiment, the formulation is in the form of lozenges, tablets, effervescent tablets, effervescent sachets, orally disintegrating tablets, sublingual tablets, buccal tablets, capsules or syrup. In one preferred embodiment, the formulation is in the form of lozenges.

In another embodiment, the composition is maintained in contact with the mouth and/or throat for a sufficient length of time that reduction of the severity or presence of one or more symptoms of the cold is achieved. The lozenges of this invention may be of any shape.

In another embodiment, the composition is maintained in contact with the mouth and/or throat for a sufficient length of time that infection by cold viruses is prevented.

In one embodiment, the amount of propolis extract is between 0.005% and 10.00%, preferably between 0.01 % and 5.00%, more preferably 0.01% and 1.00% by weight of the formulation.

In one embodiment, the amount of berberis vulgaris extract is between 0.005% and 10.00%, preferably between 0.01% and 5.00% and more preferably between 0.01% and 0.50% by weight of the total formulation.

According to these embodiments, the weight ratio of propolis extract to berberine is between 0.01 and 100, preferably between 0.10 and 10.00 and more preferably between 0.2 and 2.0. It was observed that this had a synergistic effect on the physical stability of said formulation. Thus, by providing an improved physical stability; the quality, reliability, and the shelf life of the formulation according to the present invention are increased.

Adding extract of another herbal agent, namely Pelargonium sidoides, into the formulation, improved the physical stability of the product were maintained for a longer time. Moreover, the efficacy of the formulation is enhanced by the therapeutic effects of each herbal extract used here.

In one embodiment, the formulation further comprises at least one additional herbal extract which is selected from the group comprising pelargonium sidoides, ginseng, glycyrrhiza glabra, echinacea purpurea, tilia, zingiber officinale, citrus junos, licorice, hedera helix, ginkgo biloba, turmeric, capsicum, sage, rosemary, maca, rhodiola or mixtures thereof. In one preferred embodiment, at least one additional herbal extract is selected from the group comprising pelargonium sidoides, ginseng, glycyrrhiza glabra, echinacea purpurea, tilia, zingiber officinale, citrus junos or mixtures thereof.

Since the stability and therapeutic effectiveness of the composition is influenced by the choice of the herbal extracts, the herbal extracts which are used in this present invention, are very important.

In one preferred embodiment, herbal extracts are pelargonium sidoides, ginseng, glycyrrhiza glabra, echinacea purpurea, tilia and zingiber officinale.

In one preferred embodiment, at least one additional herbal extract is pelargonium sidoides.

According to this preferred embodiment, the amount of pelargonium sidoides is between 0.10% and 10.00%, preferably between 0.20% and 5.00% and more preferably between 0.20% and 2.00% by weight of the formulation.

In one embodiment, the formulation further comprises dried honey.

In one embodiment, using honey in solidified form (dried honey) also increases the stability of the formulation. During the development study of the present invention, it was found that using dried honey instead of honey, improves the physical stability of the product.

According to this present invention, the amount of dried honey is between 25.00% and 99.00%, preferably between 50.00% and 99.00%, more preferably between 75.00% and 99.00% by weight of the total formulation.

When dried honey is used in especially these amounts, it is observed that the patient compliance is improved due to the pleasant taste of dried honey.

In one preferred embodiment, at least one additional herbal extract is zingiber officinale. According to this preferred embodiment, the amount of zingiber officinale is between 0.005% and 10.00%, preferably between 0.01% and 5.00%, more preferably between 0.01 % and 1.00% by weight of the total composition.

In one preferred embodiment, at least one additional herbal extract is glycyrrhiza glabra.

According to this preferred embodiment, the amount of glycyrrhiza glabra is between 0.01 % and 10.00%, preferably between 0.05% and 5.00%, more preferably between 0.05% and 0.50% by weight of the total composition.

In one preferred embodiment, at least one additional herbal extract is echinacea purpurea.

According to this preferred embodiment, the amount of echinacea purpurea extract is between 0.01 % and 10.00%, preferably between 0.05% and 5.00%, more preferably between 0.05% and 0.50% by weight of the total composition.

In one preferred embodiment, at least one additional herbal extract is tilia.

According to this preferred embodiment, the amount of tilia extract is between 0.01% and 10.00%, preferably between 0.05% and 5.00%, more preferably between 0.05% and 0.50% by weight of the total composition.

Here, it was found that when the above indicated amounts of herbal extracts were added to a formulation according to the present invention, the need to include a preservative in said formulation was avoided due to the characteristic features of these extracts, particularly the antibacterial, antiviral, and/or antioxidative features of the same. Thus, when a formulation according to the present invention contains the above indicated amounts of herbal extracts, the physical stability thereof can be maintained for a longer time without containing a preservative and a more natural formulation can be obtained as compared to the formulation comprising a preservative.

All plant extracts comprised in the content of the formulation within the scope of the present invention can be obtained from the shell, leaf, flower, root or seed of respective plants.

Prior art methods are used for obtaining all the extracts according to the present invention. In one embodiment, the composition further comprises zinc sulfate monohydrate.

Zinc is used for treating the common cold and recurrent ear infections, and preventing lower respiratory infections. It can also help shorten the length of colds.

In one embodiment, the composition may further comprise silver solution.

Silver solution is used in the treatment and alleviation of the symptoms of cold.

Flavouring agent used according to the present invention is selected from the group comprising but not limited to, eucalyptus, menthol, peppermint, lime, apple, cinnamon, chocolate, vanillin and fruit essences such as cherry, orange, strawberry, grape, tutti frutti.

In one embodiment, the amount of the flavouring agent is between 0.05% and 5.00% by weight of the total composition.

In one preferred embodiment, the flavouring agent is eucalyptus.

Eucalyptus species which have analgesic and anti-inflammatory activities are also widely used in modern cosmetics, food, and pharmaceutical industries. Since eucalyptus has antibacterial and anticeptic qualities, it has been shown to protect against microbial growth that can promote a host of different symptoms and diseases in the body. In this present invention, one important reason that the inventors preferably use eucalyptus is that it creates a cooling and refreshing effect.

When eucalyptus is used as the flavouring agent, it is observed that it shows a supporting effect for said formulation due to the refreshing, cooling and smoothening effect of scent and the patients administered with said formulation feels instant relief and alleviation of symptoms, thus, it helped them feel better within a shorter period of time.

According to an embodiment of the present invention, said formulation comprises;

a) propolis extract

b) berberis vulgaris extract

According to one embodiment of the present invention, said formulation comprises; a) propolis extract in the amount of between 0.005% and 10.00%

b) berberis vulgaris extract in the amount of between 0.005% and 10.00%, c) pelargonium sidoides extract in the amount of between 0.10% and 10.00%, by weight of the formulation.

a) propolis extract in the amount of between 0.005% and 10.00%

b) berberis vulgaris extract in the amount of between 0.005% and 10.00%, c) dried honey in the amount of between 25.00% and 99.00%, by weight of the formulation

a) propolis extract

b) berberis vulgaris extract

c) at least one additional herbal extract

a) propolis extract

b) berberis vulgaris extract

c) pelargonium sidoides extract

d) dried honey

a) propolis extract

b) berberis vulgaris extract

c) dried honey

d) at least one additional herbal extract

e) zinc sulfate monohydrate

f) eucalyptus

a) propolis extract

b) berberis vulgaris extract

c) dried honey

d) at least one additional herbal extract

e) zinc sulfate monohydrate f) silver solution (optionally)

g) eucalyptus

a) propolis extract

b) berberis vulgaris extract

c) dried honey

d) at least one additional herbal extract which are selected from the group comprising pelargonium sidoides, ginseng, glycyrrhiza glabra, echinacea purpurea, tilia, zingiber officinale, berberis vulgaris, citrus junos (yuzu)

e) zinc sulfate monohydrate

f) eucalyptus

a) propolis extract

b) berberis vulgaris extract

c) dried honey

e) zinc sulfate monohydrate

f) silver solution (optionally)

g) eucalyptus

According to one embodiment of the present invention, said formulation comprises:

a. propolis extract 0.005-10.00%

b. berberis vulgaris extract 0.005-10.00%

c. dried honey 25.00-99.00%

d. pelargonium sidoides extract 0.10-10.00%

e. glycyrrhiza glabra extract 0.01 -10.00%

f. echinacea purpurea extract 0.01 -10.00%

g. panax ginseng extract 0.01 -10.00%

h. tilia extract 0.01 -10.00%

i. zingiber officinale extract 0.005-10.00%

j. zinc sulfate monohydrate 0.05-5.00%

k. eucalyptus 0.05-5.00 According to one embodiment of the present invention, said formulation comprises: a. propolis extract 0.005-10.00%

b. berberis vulgaris extract 0.005-10.00%

c. dried honey 25.00-99.00%

d. pelargonium sidoides extract 0.10-10.00%

e. glycyrrhiza glabra extract 0.01 -10.00%

f. echinacea purpurea extract 0.01 -10.00%

g. panax ginseng extract 0.01 -10.00%

h. tilia extract 0.01 -10.00%

i. zingiber officinale extract 0.005-10.00%

j. citrus junos extract 0.05-10.00%

k. zinc sulfate monohydrate 0.05-5.00%

L. silver solution 0-0.50%

m. eucalyptus 0.05-5.00%

Example 1 : Lozenge

Example 2: Lozenge

Example 3: Lozenge

Example 4: Lozenge

Example 5: Lozenge

Example 6: Lozenge

The solid oral compositions mentioned above are prepared by following these steps: a. Preparing dried honey by a physical method in which microwave or heat is used b. Weighing each herbal extract, zinc sulfate monohydrate, silver solution and

eucalyptus

c. Adding all ingredients to the dried honey and mixing

d. Transfering the mixture to the feed reservoir

e. Filling the mixture to the moulding machine to form lozenges

f. Cooling the lozenges

g. Packing the lozenges into suitable packaging

In one embodiment, the solid oral composition comprises one lubricant. According to this embodiment, the solid oral composition can be prepared by following these steps: a. Mixing all ingredients

b. Adding a lubricant to this mixture

c. Compressing this mixture to form lozenges Example 7: Effervescent tablet

The effervescent tablet composition mentioned above is prepared by following these steps: a. Mixing all ingredients except for sodium stearyl fumarate

b. Adding sodium stearyl fumarate to this mixture and mixing

c. Compressing this mixture to form effervescent tablets

Example 8: Tablet or capsule

The tablet or capsule composition mentioned above is prepared by following these steps: a. Mixing dried honey, the herbal extracts, propolis extracts, zinc sulfate

monohydrate, mannitol and croscarmellose sodium

b. Adding silicon dioxide to this mixture and mixing

c. Adding magnesium stearate to the mixture and mixing

d. Compressing the mixture to form tablets or filling the mixture into capsules

Example 9: Oral solution/Syrup

The oral solution/syrup composition mentioned above is prepared by following these steps: a. Mixing water, trisodium citrate dihydrate and citric acid monohydrate to form the tampon citrate

b. Adding maltitol solution and glycerin to this obtained solution

c. Mixing the solution until homogeneous

d. Heating this homogeneous solution

e. Adding methyl paraben and propyl paraben to this solution and mixing until homogeneous

f. Cooling the solution at room temparature

g. Adding the all other ingredients to the solution and mixing

h. Filtering the solution

i. Filling the solution into bottles under nitrogen gas

Example 10: Effervescent sachet

The oral solution/syrup composition mentioned above is prepared by following these steps:

a. Mixing the herbal extracts, propolis extracts, zinc sulfate monohydrate, dried

honey, citric acid monohydrate, tartaric acid, soduim bicarbonate and sodium citrate dihydrate

b. Drying this mixture in an oven at 105 ^eC

c. Sieving the dried granules

d. Adding xylitol, sucralose, thaumatin to these granules and mixing until

homogenous

e. Filling the mixture into appropriate sachet packages

Claims

1. A formulation comprising propolis extract and berberis vulgaris extract.

2. The formulation according to claim 1 , wherein the amount of propolis extract is between 0.005% and 10.00%, preferably between 0.01% and 5.00%, more preferably 0.01% and 1.00% by weight of the formulation.

3. The formulation according to claim 1 , wherein the amount of berberis vulgaris extract is between 0.005% and 10.00%, preferably between 0.01% and 5.00% and more preferably between 0.01% and 0.50% by weight of the total formulation.

4. The formulation according to claim 1 to 3, wherein said formulation is administered by oral, parenteral, ocular, nasal, buccal, sublingual or topical route.

5. The formulation according to claim 4, wherein the formulation is preferably administered by oral route.

6. The formulation according to claim 5, wherein the formulation is in the form of lozenges, tablets, effervescent tablets, effervescent sachets, orally disintegrating tablets, sublingual tablets, buccal tablets, capsules or syrup

7. The formulation according to claim 6, wherein the formulation is in the form of lozenges.

8. The formulation according to claim 1 to 3, wherein the weight ratio of propolis extract to berberis vulgaris extract is between 0.01 and 100, preferably between 0.10 and 10.00 and more preferably between 0.2 and 2.0.

9. The formulation according to claim 1 , wherein the formulation further comprising at least one additional herbal extract which is selected from the group comprising pelargonium sidoides, ginseng, glycyrrhiza glabra, echinacea purpurea, tilia, zingiber officinale, citrus junos, licorice, hedera helix, ginkgo biloba, turmeric, capsicum, sage, rosemary, maca, rhodiola or mixtures thereof.

10. The formulation according to claim 9, wherein said at least one additional herbal extract is selected from the group comprising pelargonium sidoides, ginseng, glycyrrhiza glabra, echinacea purpurea, tilia, zingiber officinale, citrus junos or mixtures thereof.

1 1. The formulation according to claim 10, wherein said at least one additional herbal extract is pelargonium sidoides extract.

12. The formulation according to claim 1 1 , wherein the amount of pelargonium sidoides is between 0.10% and 10.00%, preferably between 0.20% and 5.00% and more preferably between 0.20% and 2.00% by weight of the formulation.

13. The formulation according to any preceding claims, comprising

a. propolis extract in the amount of between 0.005% and 10.00%

b. berberis vulgaris extract in the amount of between 0.005% and 10.00%, c. pelargonium sidoides extract in the amount of between 0.10% and 10.00%, by weight of the formulation.

14. The formulation according to claim 1 or 13, wherein the composition further comprising dried honey.

15. The formulation according to claim 14, wherein the amount of dried honey is between 25.00% and 99.00%, preferably between 50.00% and 99.00%, more preferably between 75.00% and 99.00% by weight of the formulation.

16. The formulation according to claim 15, comprising

a. propolis extract in the amount of between 0.005% and 10.00%

b. berberis vulgaris extract in the amount of between 0.005% and 10.00%, c. pelargonium sidoides extract in the amount of between 0.10% and 10.00%, d. dried honey in the amount of between 25.00% and 99.00%, by weight of the formulation.

17. The formulation according to claim 10, wherein the additional herbal extract is zingiber officinale.

18. The formulation according to claim 10, wherein the additional herbal extract is glycyrrhiza glabra.

19. The formulation according to claim 10, wherein the additional herbal extract is echinacea purpurea.

20. The formulation according to claim 10, wherein the additional herbal extract is tilia.

21. The formulation according to claim 1 , wherein the formulation further comprising zinc sulfate monohydrate.

22. The formulation according to claim 1 , wherein the formulation may further comprising silver solution.

23. The formulation according to claim 1 , wherein the formulation further comprises one flavouring agent which is selected from a group comprising eucalyptus, menthol, peppermint, lime, apple, cinnamon, chocolate, vanillin and fruit essences such as cherry, orange, strawberry, grape, tutti frutti or mixtures thereof.

24. The formulation according to claim 23, wherein the flavouring agent is eucalyptus.

25. The formulation according to any of the preceding claims, wherein the formulation comprising; a. propolis extract 0.005-10.00%

b. berberis vulgaris extract 0.005-10.00%

c. dried honey 25.00-99.00%

d. pelargonium sidoides extract 0.10-10.00%

e. glycyrrhiza glabra extract 0.01 -10.00%

f. echinacea purpurea extract 0.01 -10.00%

g. ginseng extract 0.01 -10.00%

h. tilia extract 0.01 -10.00%

i. zingiber officinale extract 0.005-10.00%

j. zinc sulfate monohydrate 0.05-5.00%

k. eucalyptus 0.05-5.00

26. The formulation according to any of the preceding claims, wherein the composition comprising; a. propolis extract 0.005-10.00%

b. berberis vulgaris extract 0.005- 10.00%

c. dried honey 25.00-99.00%

d. pelargonium sidoides extract 0.10-10.00%

e. glycyrrhiza glabra extract 0.01 -10.00%

f. echinacea purpurea extract 0.01 -10.00%

g. panax ginseng extract 0.01 -10.00%

h. tilia extract 0.01 -10.00%

i. zingiber officinale extract 0.005-10.00%

j. citrus junos extract 0.05-10.00%

k. zinc sulfate monohydrate 0.05-5.00%

L. silver solution 0-0.50%

m. eucalyptus 0.05-5.00%