AU2021103872A4

AU2021103872A4 - Immunomodulation

Info

Publication number: AU2021103872A4
Application number: AU2021103872A
Authority: AU
Inventors: Rezal Kusumaatmadja; Helder Marcal; Rezky Pontoh; Nico Wanandy
Original assignee: Individual
Current assignee: Individual
Priority date: 2021-07-05
Filing date: 2021-07-05
Publication date: 2021-09-09
Anticipated expiration: 2029-07-05

Abstract

The innovation disclosure provides a method and composition of active natural ingredients, their derivatives, and combinations with natural botanical extracts. The combination comprises of ingredients providing symptomatic relief and treatment of complications associated with mammalian immune conditions. The pharmaceutical composition immunomodulates and is a pro-resolving combinatorial factor of the immune system.

Description

Title: Immunomodulation

Background Lung disease is on the highest medical conditions that affect millions of people around the world annually and is responsible for a plethora of deaths. For example, young individuals may generally suffer from lung disease and other respiratory complications that results in the death of millions of babies younger than one year of age each year around the world.

In addition, lung diseases are associated with inflammation of the lung tissue. For example, during an acute respiratory distress syndrome (ARDS), a rapid onset of progressive malfunction of the lungs occurs. This is usually associated with the malfunction of other organs due to the incapacity to uptake and limited availability of oxygen. The condition is associated with extensive lung inflammation and small blood vessel injury in all affected organs. Furthermore, ARDS is frequently advanced by trauma, sepsis (systemic infection), diffuse pneumonia, and shock. It may also be associated with surgery, and blood abnormalities. In numerous cases inflammation during lungs disease, the inflammatory response accompanies the underlying disease state and may be more dangerous than the underlying infection or trauma. Consequently, many approaches to the prevention and management of inflammation ARDS have been unsuccessful or inconclusive. In addition, many treatments are not able to improve outcome or prevented ARDS.

In addition, persistent bronchitis leads to chronic inflammation of the bronchi in the lungs. It is generally considered one of the two forms of chronic obstructive pulmonary disease (COPD), the other being emphysema. Clinically, a persistent cough produces sputum (phlegm) and mucus.

Phlegm is associated with all these conditions and is a thick, although slippery and sticky substance produced by the throat, bronchial passages, and lung tissues. Phlegm, also called sputum, contains mucus and other substances, such as dead cells, foreign particles such as dust. These are known to induce an infection. Furthermore, the build-up of phlegm and mucus collectively, leads to inflammation of the respiratory tissues and an impaired immune system.

Asthma is another example of an inflammatory disorder that causes the airways of the lungs to swell and narrow, leading to wheezing, shortness of breath, chest tightness, and coughing. This can be a chronic condition that may be caused by environmental triggers that include although not limited to, animal hair or dander, dust, changes in weather, exercise, dietary intake, mold, and pollen.

Drugs used for the treatment of such conditions such as chronic bronchitis, COPD, and asthma include, however, not limited to, smooth muscarinic acetylcholine receptor inhibitors such as ipratropium bromide; anticholinergic bronchodilators such as tiotropium; long-acting 32-adrenergic receptor agonists such as salmeterol, formoterol, and albuterol; anti-inflammatory agents such as inhaled steroids, montelukast, a leukotriene receptor antagonist (LTRA), and roflumilast, are a selective, long-acting inhibitor of the enzyme phosphodiesterase-4 (PDE-4); xanthines such as theophylline; and mucolytic agents such as bromhexine and acetylcysteine. Numerous of these agents used for the treatment of chronic bronchitis, COPD, and asthma work through receptors that are present throughout the body, thereby potentially causing undesirable side effects.

Several drugs are available for administration by inhalation that can provide some relief The administration by inhalation can somewhat increase delivery to the target site and reduce side effects. However, due to an increase of inflammation and phlegm buildup there is decreased lung function which results in improper dosing and reduced patient compliance. Therefore, innovative, and more useful pharmaceuticals are required.

In relation to inflammation of mammalian lung tissues, phlegm and mucus build-up which causes impairment of oxygen take up and bioavailability. These collectively all correlate with clinical and laboratory features such as a cytokine storm syndrome. Herein, in an embodiment, the therapeutic combination demonstrates an anti-inflammatory therapy to prevent or reduce the severity of such an immunopathology.

For example, an immunomodulating medication may be used as a composition and method to treat some phlegm associate ailments. These may mediate reduction in the inflammatory load, or prevention of an increase in phlegm build-up load, and may assist the host immune response to reduce or eliminate the inflammation and phlegm from the body. The present disclosure relates to a composition comprising a combination of such agents. Herein, in an embodiment, the combination of agents consists of a combination of natural active agents or extracts that have an anti-inflammatory effect. In addition, the embodiment utilizes a combination that mediates immunomodulation of the host immune response. For example, by stimulating cytokine expression rhythm that assists with recovery from an infection without inducing host-derived pathology such as that seen during a cytokine storm.

For instance, it is well known that mammalian host organisms have evolved an array of immune responses that are regularly successful in removing the inflammation and phlegm from the body. However, during acute respiratory disease, a "cytokine storm" may result in the overproduction of proinflammatory cytokines such as tumor necrosis factor (TNF), Interleukin (IL)-6, IL-1r and/or IL-8, which may mediate acute lung injury (ALI), or in its more severe form, acute respiratory distress syndrome (ARDS). ALI and/or ARDS may be associated with vascular hyperpermeability, multiple organ failure that can lead to death.

Corticosteroids are exemplary potent anti-inflammatory medications. Some of these may somewhat help alleviate the symptoms (for example, swelling, or shortness of breath) of inflammation. Nonsteroidal anti-inflammatory agents are also slightly effective exemplary anti-inflammatory agents however, they also cause several serious side effects.

Instead, the natural cytokine interleukin (IL-10) is a well-known immunomodulatory protein with an effective anti-inflammatory and a pro-relief factor in various model systems. This is a secreted molecule, by various cell types including, macrophages, B and T-cell lymphocytes, dendritic, mast and eosinophil cells. This immunoregulatory cytokine performs a vital role during inflammation and immune system related outcomes [1]. It has influential anti-inflammatory and immunosuppressive roles on myeloid cell functions and forms a solid basis in chronic inflammatory diseases. The role of IL-10 is evident in cellular based autoimmune diseases such as multiple sclerosis (MS), psoriasis, or its involvement in humoral-based systemic lupus erythematosus (SLE). In addition, modulation of the immune stimulatory activities by IL-10 has demonstrated a treatment ofhumoral autoimmune diseases and infectious diseases E2]. As described, IL-10 is produced by most of the innate and adaptive immune cells and is a potent anti-inflammatory cytokine. This indicates that IL-10 secretion and its actions are extremely controlled and compartmentalized. Several efforts directed at systemic administration of IL-10 to induce the modulation of autoimmune diseases e.g., rheumatoid arthritis (RA), multiple sclerosis (MS), type I diabetes and psoriasis, have produced varying and largely ambiguous effects. Furthermore, its well known thar IL-10 can promote humoral immune responses, thus, enhancing the class II expression on B cells and induction of immunoglobulin (Ig) production E3]. Concurrently, IL-10 plays a crucial role in regulating host immune responses to pathogens, in this manner, hindering damage to the host and as a result, maintaining normal tissue homeostasis. An abnormal regulation of IL-10 is linked with exacerbated immunopathology's and an increased risk for the development of autoimmune diseases E4]. For example, during an allergic reaction the production of11-10 by antigen-specific T lymphocytes leads to anergy mediated by the inhibition of CD2S-costimulatory molecule signaling on basophils, eosinophils and mast cells, thus, alleviating allergic reactions E5]. In addition, during asthmatic events, pulmonary diseases, chronic inflammation, and obstruction of the alveoli is particularly evident in smokers, where IL-10 has shown the capability of inhibiting allergen-induced airway inflammation. Furthermore, a non-specific responsiveness in asthmatic animal models have demonstrated beneficial outcomes 76].

However, the exact mechanism of IL-10 and its protective activity remains to be clarified. It

is known that IL-10 gene transfer to the airway abrogates cellular and physiological recall

response in vivo, and IL-10 does not prevent expansion or activation of T cell subsets []. Therefore, it does not abrogate the cellular-based immunity. In addition, a relative

deficiency in IL-10 production has been observed in alveolar macrophages of atopic

asthmatic patients. More important, the potential role of IL-10 secrted by regulatory T cells

in allergy and asthma has demonstrated benefits Es]. Nevertheless, the precise mechanisms

of IL-10 remain unknown.

More important, the combination herein the embodiment presents a combination of natural

and botanical extracts that induce the upregulation of IL-10 and its anti-inflammatory

effects. In addition, the inventors have discovered for the first time that the upregulation of

IL-10 has anti-phlegm activity and can minimize mucus build-up in a mammalian subject.

Natural active and medicinal plant extracts Plant and animal extracts have been used throughout thousands of years in traditional

medicinal in response to a range of ailments. For example, a variety of natural herbal agents

have demonstrated potent anti-inflammatory effects in mammals such as humans.

Moreover, these extracts have shown compelling capability to modulate the immune

response.

In fact, it is understood that 70-80 percent of the human population in developing countries

utilize medicinal plants for their primary healthcare. Moreover, a variety of phytochemicals derived from the plants have been shown to have anti-inflammatory effects in humans. More important, phytochemicals have shown to be immunomodulatory.

For the first time, the present inventors have accomplished that a combination of naturally derived active agents in combination with natural plant extracts augment specific aspects of the immune system to mediate an effective response while minimising phlegm and mucus in association with the respiratory system.

Technical specifications The disclosure relates to the use of a composition comprising and consisting of a combination of ingredients thereof selected from natural and botanicals in a formulation as a method providing temporary relief of mucus accretion, inflammation, and its associated disorders that correlate with the immune system.

Definitions Throughout this specification and the claims that follow, unless the context requires otherwise, the word "comprise", and variations such as "comprises" or "comprising", will be understood to imply the inclusion of a stated element, integer or step, or group of elements, integers, or steps, but not the exclusion of any other element, integer or step, or group of elements, integers, or steps. The term "consisting of' will be understood to be exhaustive, excluding non-recited active components of the compositions. As used herein the terms "treat" or" treatment" and variations thereof refer to any and all uses which remedy a rheumatic disorder or sports injury or at least one symptom thereof, or otherwise prevent, hinder, relieve, retard, or reverse the progression of undesirable symptoms in any way whatsoever. Thus, the terms are to be considered in their broadest context. For example, treatment does not essentially imply that a person is treated until total recovery. In conditions which are characterised by or display multiple symptoms, the treatment need not necessarily prevent, hinder, retard, or reverse all the said symptoms, but may prevent, hinder, retard, or reverse one or more of said associated symptoms.

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by those of ordinary skill in the art to which the invention belongs. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, preferred methods and materials are described. For the purposes of the present invention, the following terms are defined below.

The term "active" as used to describe "active agents" or similar herein is referring to chemicals having medicinal benefits.

The term 'anti-phlegm' as used herein is the ability of a drug or substance to suppress or reduce the ability of a phlegm build-up in a mammalian host cells.

The term 'anti-mucus' as used herein is the ability of a drug or substance to suppress or reduce the ability of a mucus build-up in a mammalian host cells.

The term "bioavailable" as used herein is ability of a drug or other substance to be absorbed and used by the body. Orally bioavailable means that a drug or other substance that is taken by mouth can be absorbed and used by the body.

The term "natural" as used in the context of "natural extract" or "natural agent" etc. as used herein is referring to an extract or agent that can be derived from a natural source, such as a plant or animal, or alternatively from other natural sources such as yeast, bacteria, etc.

The "therapeutically effective amount" will be any suitable amount that will elicit a beneficial or therapeutic effect in the subject.

The articles "a" and "an" are used herein to refer to one or to more than one (i.e., to at least one) of the grammatical object of the article. By way of example, "an element" means one element or more than one element.

As used herein, "and/or" refers to and encompasses any and all possible combinations of one or more of the associated listed items, as well as the lack of combinations when interpreted in the alternative (or).

Throughout this specification, unless the context requires otherwise, the words "comprise," "comprises" and "comprising"will be understood to imply the inclusion of a stated step or element or group of steps or elements but not the exclusion of any other step or element or group of steps or elements. Thus, use of the term "comprising" and the like indicates that the listed elements are required or mandatory, but that other elements are optional and may or may not be present. By "consisting of' is meant including, and limited to, whatever follows the phrase "consisting of'. Thus, the phrase "consisting of' indicates that the listed elements are required or mandatory, and that no other elements may be present. By "consisting essentially of' is meant including any elements listed after the phrase and limited to other elements that do not interfere with or contribute to the activity or action specified in the disclosure for the listed elements. Thus, the phrase "consisting essentially of' indicates that the listed elements are required or mandatory, but that other elements are optional and may or may not be present depending upon whether they affect the activity or action of the listed elements.

It will be appreciated that the terms used herein, and associated definitions are used for the purpose of explanation only and are not intended to be limiting.

Description of the preferred embodiments In a most preferred embodiment, the present innovation provides a composition of an effective amount of active botanical extracts as the preferred ingredients for use. Embodiments of the present disclosure also provide compositions comprising or consisting of the combination of natural extracts and natural plant ingredients for temporary treatment and relief of symptoms associated with inflammation of the respiratory system and its disorders.

The composition will be typically formulated to be suitable for oral administration. By way of example only, the composition in the form of an oil, powder, tonic water, lozenge, paste or gel.

Those skilled in the art will appreciate that the application may be varied depending on a variety of factors including, for example, the severity of the disorder, phlegm or mucus build-up, inflammation suffered by the subject, the age, general health and diet of the subject, and combination with any other treatment or therapy. The timing of administration, number of pharmaceutical, and the duration of administration may be determined by the subject and/or a consulting health professional.

The references in this specification or information derived from it, or to any matter which is

known, is not, and should not be taken as an acknowledgment or admission or any form of suggestion that the prior art (or information derived from it) or known matter forms part of

the common general knowledge in the field of endeavour to which this specification relates.

The natural and botanical active ingredients or their derivatives are useful in

pharmaceutical compositions and are safer compared to current drugs and suitable for use mammalian usage. In various embodiments, the composition of the disclosure comprises of approximately 0.1% to about 90%, more preferably 0.1% to about 70% of a cumulative

amount of the botanical active ingredients based on a total amount of the oral composition.

In addition, relative efficacious concentration of the natural and botanical active ingredients

in the composition depends upon the active compounds in the extract and the required dosing for bioavailability, hence, the concentration may vary so that the amount delivered is effective to provide the desired effects, as recognized by one of skill in the art.

In a first aspect, the present disclosure relates to an anti-phlegm and mucus composition comprising a combination of agents consisting of a curcuminoid, an emodin, bioavailable

zinc and an at least one active agent obtained from Tinospora cordfolia.

In an embodiment, the composition further comprises an agent selected from the list

consisting of an albumin, a glutathione, ascorbic acid, and bioavailable iron. In an

embodiment, at least one of the agents are provided as extracts derived from plants and/or animals,

In an embodiment, the at least one active agent obtained from T. cordfolia is provided by a

Tinospora cordifolia extract.

In an embodiment, the curcuminoid is provided by a Curcuma spp. extract.

In an embodiment, the emodin is provided by an Aloe spp. extract. In an embodiment, the bioavailable zinc is provided by a moringa extract. In an embodiment, the albumin is provided by a Channa striata (snakehead fish) extract,

In a second aspect, the present disclosure relates to a composition comprising a combination of agents consisting of a Tinospora cordfolia extract, a Curcuma xanthorrhizaextract, an aloe extract and a moringa extract. In an embodiment, the composition further comprising a Channa striata (snakehead fish) extract,

In a third aspect, the present disclosure relates to a composition comprising of a combination of agents consisting of a Tinospora cordfolia extract, a Curcuma xanthorrhiza extract, an aloe extract, a moringa extract and a Channa striataextract.

In a fourth aspect, the present disclosure relates to the build-up of phlegm when used to treat inflammation of the respiratory system. In an embodiment, the pharmaceutical alleviates and minimises mucus in a mammalian subject.

In a fifth aspect, the present disclosure relates to the use of the pharmaceutical composition of the present disclosure to treat inflamed lung tissue.

In a sixth aspect, the present disclosure relates to the use of the composition of the present disclosure in the manufacture of a medicament for the treatment of anti-phlegm or mucus in a mammalian subject.

In an embodiment, the composition is formulated for oral delivery. In an embodiment, the composition comprises a dried powder,

In an embodiment, the composition comprises an at least one active agent obtained from Tinospora cordfolia. Where the Tinospora cordifolia extract is selected from an extract selected from the group consisting of a leaf extract, a stem extract, and a root extract. T. cordfolia extract contains several phytochemicals. In an embodiment, the at least one active agent obtained from Tinospora cordfolia is selected form the list consisting of terpenoids (eg. tinosporide, furanolactone diterpene, furanolactone clerodane diterpene, furanoid diterpene, tinosporaside, ecdysterone makisterone and several glucosides isolated as polyacetate, phenylpropene disaccharides cordifolioside A, B and C, cordifoliside D and E, tinocordioside, cordioside, palmatosides C and F, sesquiterpene glucoside tinocordifolioside, sesquiterpene tinocordifolin); alkaloids (eg. tinosporine, magnoflorine, berberine, choline, jatrorrhizine, 1,2-substituted pyrrolidine, jatrorrhizine, palmatine, beberine, tembeterine); lignans (e.g., 3(a, 4-dihydroxy-3-methoxybenzyl)-4-(4- hydroxy-3-methoxybenzyl); steroids

(e.g. giloinsterol, (S), 3-Sitosterol, 20a- Hydroxy ecdysone); and other phytochemicals including columbin, Corydine, giloin, tinosporan acetate, tinosporal acetate, tinosporidine, tinosporic acid, heptacosanol, octacosanol, sinapic acid, tinosponone, tinosporal, tinosporon, two phytoecdysones, and arabinogalactan.

In an embodiment, a T. cordfolia extract comprises a plurality of phytochemicals that in combination with the other constituents herein, have an anti-phlegm and mucus effect.

Summary of the innovation According to one aspect of the disclosure, provided are compositions of botanical active ingredients derived from plants for temporary symptomatic relief of inflammation, phlegm or mucus build-up associated with lung tissue complications.

Likewise, a further aspect of the disclosure is provided in the composition comprising natural active ingredients disclosed herein to temporarily relieve inflammation associated with such conditions.

According to one aspect of the disclosure, provided are botanical active ingredients chosen from specific plants of the following the genera: T. cordfolia extract, Moringa extract, Curcuma extract, Aloe vera extract and Channa striataextract.

In a particular embodiment, the ingredients are administered in the form of capsuled powder or oil for the said applications.

The disclosure will now be described with reference to the following specific examples, which should not be construed as in any way limiting the scope of the disclosure.

Examples of innovation By way of example only, a composition for use in accordance with the present disclosure is outlined below. The following is to be construed as merely an illustrative example of a composition and not as a limitation of the scope of the disclosure in any way.

Example 1 - A composition comprising a combination of natural ingredients from the selected botanical ingredients for the treatment of symptomatic relief of the accrual of phlegm or mucus build-up associate in tissue respiratory system disorders,

Size - Net weight 100 g / 3.5 Oz

Ingredients - the following percentages:

3S% Moringa extract,

% T. Cordfolia extract,

28% Aloe vera extract,

19% Curcuma extract,

10.0% Channa striataextract

Example 2 - An oral consumable product with the said combination composition comprising of in a powder extract form thereof with selected botanical and natural extract ingredients for the treatment of symptomatic relief such as phlegm and mucus associated with respiratory disorders. Size - in a capsule form with the said composition of 500mg w/w.

The extracts of the present invention were sourced and prepared using the following methods. Raw material from plant an animal matter for extraction were obtained as follows: T. cordfolia, Curcuma, Channa striata; Aloe barbadensis; Moringa olefera. Separately, the same amount of each of the extracts may be individually prepared as above (i.e., without combination), and packaged into sachets and the sachets contain the same amount of an individual extract as that extract in combination, that is:

* 1000 mg Moringa extract,

* 200 mg T. Cordfolia extract,

* 1000 mg Aloe vera extract,

* 300 mg Curcuma,

* 500 mg Channa striata

Prophetic Example:

The anti-inflammatory composition were tested in a human colon fibroblast cell line Hs i. Int (ATCC CRL-7820; obtained from ATCC, Australia) cultured in Dulbecco's Modified Eagle's Medium (DMEM) plus 5-10% fetal bovine serum (FBS, both sourced obtained from ATCC, Australia). The CRL7820 cell line expresses high levels of the ACE-2 receptor (Hikmet et al., 2020), which is the entry point into cells for SARS-Cov and SARC-Cov-2.

The FBS contains albumin in the serum in the range of 4.5 mg/mL. Briefly, cultured at

37°C with 5% CO2 and culture supernatants are tested using a multiplex interleukin assay

in accordance with manufacturer's instructions and compared to negative control

supernatant.

Methods:

PBMC samples were obtained from healthy subjects and cultured in six different

concentrations of extract combinations following the stimulation with lipopolysaccharide

(LPS). Supernatants from each of these conditions were pooled and tested using a Human

Multiplex Panel (Cat # EPX450-12171-901) to analyse cytokine production.

In vitro experimental protocol

• Reconstitute extracts in DMSO. Filter sterilized,

• Thaw PBMC and resuspend in culture medium,

• Plate out cells (100 pl) into 96-well plate,

• Rest overnight in 37°C/5% CO 2 incubator (approximately 16-18 hours)

• Wash PBMC, remove supernatants and re-suspend in 100 pl fresh culture medium

in the presence of 10% heat inactivated FBS,

• Add extracts / controls in 50 pl. Incubate at37C/5% CO2 for 30 mins (150pl in

each well)

• Add LPS/PBS in 10 tl to appropriate wells (final 160,pl in each well, total)

• Incubate plate at 370 C/5% CO 2 for 24 hours

• Samples are collected and stored at -80°C before analyzing the analytes.

PBMC - 2.5 x 10/well (total = 3.1 x 107 cells) per experiment (6.2 x 107 cells total per subject), *Extracts (stock concentration = 40 mg/ml in DMSO = 40 000 tg/ml), *LPS (stock I mg/ml), and final concentration of LPS used as positive control for inflammation is

ng/mL), * Control: PBMC stimulated with LPS in the presence of DMSO, with and without dexamethasone. #Culture medium RPMI medium (supplemented with glutamax) with 1x PenStrep and 2.5 pg/ml plasmocin 10% heat inactivated FBS *Each well contained 100 pl of cells + 50 pl of diluted product or control + 10 pl LPS/PBS = 160 pl volume / well. Each condition was plated in triplicate, note; final concentration of DMSO was kept at 0.5% (v/v).

References

1. Yiu, H.H., A.L. Graham, and R.F. Stengel, Dynamics of a cytokine storm. PLoS One,

2012. 7(10): p. e45027.

2. Beebe, A.M., D.J. Cua, and R. de Waal Malefyt, The role of interleukin-10 in

autoimmune disease: systemic lupus erythematosus (SLE) and multiple sclerosis (MS).

Cytokine Growth Factor Rev, 2002. 13(4-5): p. 403-12.

3. Saxena, A., et al., Interleukin-10 paradox:.A potent immunoregulatory cytokine that has

been difficult to harnessfor immunotherapy. Cytokine, 2015. 74(1): p. 27-34.

4. Iyer, S.S. and G. Cheng, Role of interleukin 10 transcriptionalregulationin inflammation

and autoimmune disease. Critical reviews in immunology, 2012. 32(1): p. 23-63.

5. Chung, F., Anti-inflammatory cytokines in asthma and allergy: interleukin-10, interleukin

12, interferon-gamma. Mediators Inflamm, 2001. 10(2): p. 51-9.

6. Li, C., I. Corraliza, and J. Langhorne,A defect in interleukin-10 leads to enhanced

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67(9): p. 4435-42.

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and in smokers. Eur Respir J, 1999. 14(2): p. 309-14.

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Claims

EDITORIAL NOTE

2021103872

THERE IS ONE PAGE OF CLAIMS ONLY

CLAIMS 1. A pharmaceutical composition and method of treatment with a therapeutically effective amount of a combination of natural extracts and constituents comprising of curcuma extract, Moringa extract, Tinospora cordzfolia extract, Aloe vera extract an emodin, zinc, ascorbic acid, Channa striataextract, albumin, glutathione, ascorbic acid, iron and administering the combination for immunomodulating a mammalian subject by enhancing interleukin-10 in the subject and providing the alleviation of symptomatic relief of phlegm or mucus accumulation associated with a lung tissue diseases.
2. A composition according to claim 1, with an effective amount ranging from 0.1 to 99.0% relative to total weight when in a solid form or relative to the volume when in liquid form such as fortified or infused oil or water, or in a solid form of a a) capsule, b) pill, c) powder,
3. An application as a method of modulating the immune system according to claim 1 with an effective amount of composition as said in claim 2, for in vivo usage on a mammalian subject for modulating symptomatic relief from the selected group of conditions consisting of,

a) bronchitis b) chronic obstruction pulmonary disease c) Smoking associated hyperplasia of the goblet cells

d) Acute obstructive airways disease
4. A method and composition according to claim 1, 2 and 3 in a form an oil, gel, ointment, serum, lozenge, nutrition supplement for consumption, or nasal spray.
5. A method of enhancing the production of the cytokine interleukin-10 in a mammalian subject with an inflammatory lung disease, comprising administering to the subject with a therapeutically effective amount of the composition, according to claim 1,2,3 and4 and for alleviation of a disease such as in pulmonary fibrosis, pneumonia, or pulmonary sarcoidosis.

FIGURE 1 Jul 2021

The therapeutic composition demonstrates anti-inflammatory activity by inducing IL-10 that enables the maintenance of homeostasis in the immune response.

* ** 2021103872

Figure 1. Utilizing 5 μg/mL of extract against the LPS-stimulated cells, the level of IL-10 increases significantly by 34.65%-fold and 36.95%-fold, compared to dexamethasone and LPS (*p<0.05) and DMSO+LPS (**p<0.05) controls, respectively.

FIGURE 2 Jul 2021

Summary of analytes level changes as a percentage of extract combination demonstrate that 5 μg/mL is suffice to induce immunomodulation.