Composition comprising algal proteoglycan extract and uses thereof

Abstract

The present application provides the use of algal proteoglycan extract and the composition containing algal proteoglycan extract in the preparation of a medicament for treating or preventing tumors, pain, inflammation or inflammation factor-mediated diseases.

Description

TECHNICAL FIELD

[0001] The present application relates to compositions comprising an extract of algae and uses thereof, in particular, to a composition comprising an extract of algal proteoglycan and uses thereof in treating or preventing a tumor, pain, inflammation or inflammation factor mediated diseases. BACKGROUND

[0002] Pancreatic cancer is a highly malignant digestive tract tumor with a very poor prognosis. Diagnosis and treatment of pancreatic cancer are difficult. About 90% of pancreatic cancer is ductal adenocarcinoma originating from glandular epithelium. The incidence and mortality of pancreatic cancer have increased significantly in recent years, and the 5-year survival rate is <1%, which is one of the malignant tumors with the worst prognosis. The early diagnosis rate of pancreatic cancer is not high, the surgical mortality is high, and the cure rate is very low. In recent years, the incidence and mortality of other cancers have also continued to rise.

[0003] Seeking an effective anti-tumor drug is the key to treating cancer, especially pancreatic cancer, and is the focus of current research.

[0004] Since the 1970s, people have paid more and more attention to algae, especially blue-green algae. Initially, researchers focused on the nutritional value and toxicity of algae. At the 1974 United Nations Food and Agriculture Organization Conference, Spirulina was considered to be an excellent food resource for humans in the future. The understanding of the medicinal effects of algae began in the 1980s, and people mainly focused on the properties of various algae extracts. Among these studies, the extracts of blue-green algae, especially Spirulina, were particularly noteworthy. The present inventors extracted an algal proteoglycan extract from algae, as described in Chinese Patent CN1098707C. The inventors studied the therapeutic effects of this extract on cancer, particularly pancreatic cancer, and on pain (such as tumor-related pain) and inflammation (such as tumor-related inflammation) in the present application. SUMMARY

[0005] In one aspect, the present application provides the use of an algal proteoglycan extract or a composition comprising an algal proteoglycan extract in the preparation of a medicament for treating or preventing pancreatic cancer in an individual. The pancreatic cancer is a primary cancer or a metastatic cancer.

[0006] The present application also provides the use of an algal proteoglycan extract or a composition comprising an algal proteoglycan extract in the preparation of a medicament for treating or preventing inflammation or pain. In certain embodiments, the above-mentioned inflammation is tumor-related inflammation, and the above-mentioned pain is tumor-related pain.

[0007] In another aspect, the present application provides a method for treating or preventing pancreatic cancer in a subject, comprising administering to the subject a therapeutically or prophylactically effective amount of an alginate proteoglycan extract or a composition comprising the alginate proteoglycan extract. The present application also provides a method for treating or preventing inflammation or pain in a subject, comprising administering to the subject a therapeutically or prophylactically effective amount of an alginate proteoglycan extract or a composition comprising the alginate proteoglycan extract.

[0008] In one aspect, the present application provides an alginate proteoglycan extract or a pharmaceutical composition comprising the alginate proteoglycan extract for use in treating or preventing pancreatic cancer, pain or inflammation in a subject.

[0009] In certain embodiments, the alginate proteoglycan extract and / or the same together with one or more pharmaceutically acceptable carriers are formulated into a pharmaceutically acceptable dosage form, preferably oral liquid, tablet, granule, capsule, powder, pill, syrup, injection, etc.

[0010] In certain embodiments, the alginate proteoglycan extract is administered orally, subcutaneously, intramuscularly or intraperitoneally. In preferred embodiments, the alginate proteoglycan extract is administered orally.

[0011] In certain embodiments, the alginate proteoglycan extract is administered at a dose of 5-500 mg / kg body weight per day. In preferred embodiments, the above-mentioned administration dose is 10-150 mg / kg body weight. In more preferred embodiments, the above-mentioned administration dose is 20-120 mg / kg body weight.

[0012] In another aspect, the present application provides the use of an alginate proteoglycan extract or a composition comprising the alginate proteoglycan extract in the manufacture of a medicament for treating or preventing inflammation factor-mediated related diseases.

[0013] In another aspect, the present application provides a pharmaceutical composition comprising an alginate proteoglycan extract and one or more other anti-tumor drugs.

[0014] In some embodiments, the above-mentioned pharmaceutical composition comprising an alginate proteoglycan extract and one or more other anti-tumor drugs is used for treating or preventing tumors in a subject, preferably pancreatic cancer, melanoma or sarcoma. The alginate proteoglycan extract and the other anti-tumor drugs have a synergistic effect in tumor treatment, significantly enhancing the effect of treating tumors.

[0015] In another aspect, the present application also provides the use of a pharmaceutical composition comprising an alginate proteoglycan extract and one or more other anti-tumor drugs in the manufacture of a medicament for treating or preventing tumors in a subject.

[0016] In yet another aspect, the present application provides a method for treating or preventing a tumor in a subject, comprising administering to the subject a therapeutically or prophylactically effective amount of an algal proteoglycan extract or a pharmaceutical composition comprising the algal proteoglycan extract and one or more other anti-tumor agents.

[0017] In certain embodiments, the tumor is a primary cancer or a metastatic tumor. In preferred embodiments, the tumor is selected from the group consisting of pancreatic cancer, melanoma, sarcoma, leukemia, lung cancer, esophageal cancer, lymphoma, gastric cancer, liver cancer, breast cancer, colon cancer, skin squamous cancer, or a metastatic tumor of the above.

[0018] The present application also provides the use of an algal proteoglycan extract-containing anti-tumor composition in anti-tumor immunity.

[0019] The algal proteoglycan extract can be prepared according to the method described in Chinese Patent CN 1098707C, the entire contents of which are incorporated herein by reference. Specifically, the method for preparing the algal proteoglycan extract comprises the following steps:

[0020] a. dissolving the dry powder of blue-green algae in 5-20 times the amount of water, and performing cell wall breaking treatment,

[0021] b. heating the obtained mixture at 60-100°C, and performing solid-liquid separation after cooling,

[0022] c. adjusting the pH value of the obtained liquid to less than 7, and performing solid-liquid separation again,

[0023] d. adjusting the obtained liquid to neutral, concentrating, and drying if necessary.

[0024] The prepared algal proteoglycan extract contains more than about 50% of proteoglycan, for example, more than about 60%, more than about 65%, more than about 70%, more than about 75% by weight, etc. In certain embodiments, the algal proteoglycan extract contains about 70%-75% of proteoglycan by weight.

[0025] BRIEF DESCRIPTION OF DRAWINGS

[0026] Figure 1 An MTS assay protocol for detecting the proliferation of PANC-1 cell line is shown.

[0027] Figure 2 The percentage of proliferation of PANC-1 cells relative to the control after treatment with different concentrations of algal proteoglycan extract on day 1 (D1), 2 (D2), 3 (D3), 4 (D4), and 6 (D6) is shown.

[0028] Figure 3 CT imaging changes of the pancreas of a patient with advanced pancreatic cancer after taking algal proteoglycan extract for 3 months are shown. DETAILED DESCRIPTION

[0029] The present application provides use of an algal proteoglycan extract or a pharmaceutical composition comprising the algal proteoglycan extract in the preparation of a medicament for treating or preventing a tumor such as pancreatic cancer, inflammation, pain or inflammation factor mediated related diseases in a subject.

[0030] The "pharmaceutically acceptable carrier" as used herein refers to a carrier that does not interfere with the biological activity of the active ingredient, and includes those conventionally used in the pharmaceutical art. The pharmaceutically acceptable carrier of the present application can be solid or liquid, including pharmaceutically acceptable excipients, buffers, emulsifiers, stabilizers, preservatives, diluents, encapsulating agents, fillers, etc. For example, the pharmaceutically acceptable buffers further include phosphate, acetate, citrate, borate and carbonate, etc.

[0031] The pharmaceutical composition of the present application can be presented in unit dosage form, and can be prepared by any method known in the pharmaceutical art. All methods include the step of bringing the active ingredient of the present application into association with one or more pharmaceutically acceptable carriers. In general, the compositions are prepared by uniformly blending the active ingredient with a liquid carrier, a solid carrier or both, and then shaping the product, if necessary.

[0032] In certain embodiments, the algal proteoglycan extract described herein and / or the same together with a pharmaceutically acceptable carrier are formulated into a pharmaceutically acceptable dosage form, such as oral liquid, capsule, powder, tablet, granule, pill, syrup, injection, suppository, etc.

[0033] The preparation of the algal proteoglycan extract described herein is carried out according to the method described in Chinese Patent CN1098707C, the entire contents of which are incorporated herein by reference.

[0034] In certain embodiments, the algal proteoglycan extract of the present application is administered at a dose of 5-500 mg / kg body weight per day, preferably 20-150 mg / kg body weight, more preferably 20-120 mg / kg body weight, such as 20 mg / kg body weight, 30 mg / kg body weight, 60 mg / kg body weight, 120 mg / kg body weight, etc.

[0035] In another aspect, there is provided a method for treating or preventing a tumor such as pancreatic cancer, inflammation, pain or inflammation factor mediated related diseases in a subject, which comprises administering to the subject a therapeutically or prophylactically effective amount of an algal proteoglycan extract or a composition comprising the same.

[0036] In yet another aspect, there is provided use of a therapeutically or prophylactically effective amount of an alginate proteoglycan extract or a composition comprising the alginate proteoglycan extract in the treatment or prevention of cancer, inflammation or pain or inflammation factor-mediated related diseases in a subject.

[0037] As used herein, "treatment" includes inhibiting, curing, reducing or alleviating cancer, pain (e.g. tumor-related pain) or inflammation (e.g. tumor-related inflammation) or inflammation factor-mediated related diseases and preventing or delaying metastasis of a primary cancer.

[0038] In certain embodiments, the cancer can be a primary cancer or a metastatic cancer. In some embodiments, the cancer can be pancreatic cancer, liver cancer, colon cancer, gastric cancer, melanoma, sarcoma, leukemia, lung cancer, breast cancer, skin squamous carcinoma, esophageal cancer, lymphoma, etc.

[0039] In some embodiments, the inflammation factor includes, but is not limited to, histamine receptor H3, kallikrein-related peptidase 3, kallikrein-related peptidase 13, insulin-like growth factor 2, tumor necrosis factor, leukotriene B4 receptor 2, chemokine (C-C motif) ligand 4, colony-stimulating factor 3 (granulocyte), dopamine receptor 4, platelet-derived growth factor beta polypeptide, kallikrein-related peptidase 11, kallikrein-related peptidase 15, leukotriene B4 receptor, leukotriene C4 synthase, chemokine (C-C motif) ligand 2, interleukin-6, interleukin-10, interferon-alpha receptor 2, platelet-derived growth factor A, platelet-derived growth factor C, platelet-derived growth factor D, C-reactive protein, kallikrein-related peptidase 14, bradykinin receptor B2, tumor necrosis factor (ligand) superfamily member 11, chemokine (C-C motif) ligand 3, chemokine (C-C motif) ligand 7, chemokine (C-C motif) ligand 20, chemokine (C-X-C motif) ligand 2, platelet-derived growth factor beta polypeptide, interferon (alpha, beta and omega) receptor 1, interleukin 3, interleukin 9, interleukin 17B, interleukin 20, growth differentiation factor 2, growth differentiation factor 3, macrophage migration inhibitory factor (glycosylation-inhibiting factor), growth differentiation factor 11, bone morphogenetic protein 2, bone morphogenetic protein 4, thrombopoietin, kallikrein-related peptidase 4, kallikrein-related peptidase 5, bradykinin receptor B1, and interferon-alpha 6, etc.

[0040] In some embodiments, the inflammation factor-mediated disease or disorder includes, but is not limited to, chronic inflammation of the bladder, urethritis, vestibular vertigo, allergic reactions, asthma (bronchial asthma, childhood asthma), liver cancer (human hepatocellular carcinoma, primary liver cancer, etc.), prostate cancer, ovarian cancer, cervical cancer, breast cancer, testicular cancer, colorectal cancer, osteoarthritis, essential hypertension, myocardial infarction, Parkinson's disease, Alzheimer's disease, hereditary angioedema, hemangioma (infant), cardiovascular disease, colon cancer, purulent meningitis, endometrial cancer, spontaneous abortion, bladder cancer, brain glioma, liver fibrosis, cerebral hemorrhage, non-small cell lung cancer, acute myelocytic leukemia, cerebral infarction, pharyngeal tonsil hypertrophy, hepatitis C, multiple myeloma, systemic lupus erythematosus, pneumonia (bronchial pneumonia, pediatric pneumonia, community-acquired pneumonia), ulcerative colitis, chronic obstructive pulmonary disease, tuberculosis, Parkinson's disease, non-alcoholic fatty liver disease, hypertension (obesity hypertension, essential hypertension), autoimmune hepatitis, sclerosing cholangitis, normal weight obesity syndrome, diabetic retinopathy, inflammatory bowel disease, hypersomnia, Behcet's disease, giant cell arteritis, squamous cell carcinoma, basal cell carcinoma, cutaneous mucosa lymph node syndrome, colitis, allergic disease, pancreatic cancer, ovarian cancer, gastric cancer, stroke (cerebral stroke, ischemic stroke), drug-induced acute liver injury, chronic neutrophilic leukemia, schizophrenia, thyroid papillary carcinoma, meningioma, diabetes (type 1 diabetes, type 2 diabetes), pulmonary thromboembolism, thyroiditis, multiple myeloma bone disease, chronic lymphocytic leukemia, chondrosarcoma, oral leukoplakia and squamous carcinoma, allergic rhinitis, chronic sinusitis, listeria infection, myocarditis, multiple sclerosis, multiple myeloma, laryngeal cancer, IgA nephropathy, viral myocarditis, colorectal cancer, psoriasis, discogenic low back pain, hepatitis B, lung cancer, pulpitis, Hashimoto's thyroiditis, thyroid papillary carcinoma, tuberculosis, leukemia, Kawasaki disease, aplastic anemia, polymyositis, Hodgkin's disease, myeloid leukemia, ankylosing spondylitis, chronic rhinosinusitis with nasal polyps, diffuse large B-cell lymphoma, atopic dermatitis, high altitude chronic pulmonary heart disease, arthritis (osteoarthritis, rheumatoid arthritis, juvenile idiopathic arthritis, spondylarthritis), non-small cell lung cancer, allergic rhinitis, flat morphea, unstable angina pectoris, acute coronary syndrome, periodontitis, coronary heart disease, atherosclerosis, teratocarcinoma, embryonal carcinoma, atopic dermatitis, endometrial cancer, acute pancreatitis, cervical squamous carcinoma, oral squamous carcinoma, nasopharyngeal carcinoma, esophageal squamous carcinoma, myelodysplastic syndrome, cerebral gliomatosis, primary Sjogren's syndrome, anemia (childhood aplastic anemia, aplastic anemia), cerebral palsy, neonatal hypoxic ischemic encephalopathy, airway inflammation, obstructive sleep apnea hypopnea syndrome, gout, tonsillitis, acute respiratory distress syndrome, obsessive-compulsive disorder, non-alcoholic fatty liver, metabolic syndrome, neonatal sepsis, hand-foot-mouth disease, dermatomyositis, sepsis, encephalitis, eclampsia,Biliary duct cancer (perihilar biliary duct cancer, diabetic macroangiopathy biliary duct cancer), systemic sclerosis, colon cancer, polycystic ovary syndrome, Netherton syndrome, coeliac disease, diabetic nephropathy, etc.

[0041] The "therapeutically effective amount" or "prophylactically effective amount" used herein can be determined according to the specific situation, and can be easily grasped by those of ordinary skill in the art according to the actual amount of drug required, for example, can be determined according to the body weight, age, and condition of the patient. Since the extract is a non-toxic component, it can be administered directly as an extract as needed, in which case the composition does not contain a pharmaceutically acceptable carrier. When the composition contains a pharmaceutically acceptable carrier, they can be mixed according to conventional methods in the pharmaceutical field to prepare the desired drug.

[0042] In certain embodiments, the algal proteoglycan extract or the composition comprising the algal proteoglycan extract is administered orally, subcutaneously, intramuscularly, or intraperitoneally. In preferred embodiments, the algal proteoglycan extract or the composition comprising the algal proteoglycan extract is administered orally.

[0043] The present application also provides a pharmaceutical composition comprising the algal proteoglycan extract and one or more other anti-tumor drugs.

[0044] The above-mentioned anti-tumor drugs include those clinically used for the treatment of tumors, for example, including nucleotide synthesis inhibitors (such as 5-fluorouracil (5-FU)), anti-tumor antibiotics (such as doxorubicin (ADM)), platinum compounds (such as carboplatin), alkylating agents (such as cyclophosphamide and nitrosoureas such as carmustine), DNA polymerase inhibitors (such as gemcitabine), drugs that interfere with protein synthesis (such as etoposide (VP-16)), and the like.

[0045] The anti-tumor effect of the algal proteoglycan extract in combination with one or more other anti-tumor drugs is significantly enhanced, showing a synergistic effect. The synergistic effect of combination therapy (e.g., the combination of the algal proteoglycan extract and one or more other anti-tumor drugs) allows for the administration of a lower dose to an individual with a condition (e.g., cancer or a related symptom thereof) than the dose of the individual therapy alone, and / or reduces the frequency of administration of the therapy.

[0046] The "individual" described herein refers to a mammal, including but not limited to primates, cows, horses, pigs, sheep, goats, dogs, cats, and rodents such as rats and mice.

[0047] In the specification and claims, the words "comprise", "contain", and "include" mean "including but not limited to", and are not intended to exclude other parts, additives, components, or steps.

[0048] It should be understood that the features, characteristics, components, or steps described in a particular aspect, embodiment, or example of the invention may be applied to any other aspect, embodiment, or example described herein, unless there is any contradiction.

[0049] The foregoing disclosure generally describes the present invention, and the following embodiments further illustrate the invention. These embodiments are described merely to illustrate the invention and not to limit its scope. Although specific terms and values ​​are used herein, they are also to be understood as exemplary and do not limit the scope of the invention. Unless otherwise specified, the experimental methods and techniques described herein are methods and techniques well known to those skilled in the art. Example

[0050] Example 1 Inhibitory effect of fucoidan extract on pancreatic cancer

[0051] Example 1.1 Inhibitory effect of fucoidan extract on proliferation of PANC-1 pancreatic cancer cells

[0052] Cell lines & cell culture

[0053] In this study, the pancreatic cancer cell line PANC-1 was used. This cell line was developed by... The company cultivates the cells. After several passages to ensure cell viability and to allow the cells to undergo different assays (MTS assay and...). The amount required for analysis. The table below lists the relevant information about PANC-1 used in this application.

[0054] Table 1

[0055]

[0056] PANC-1 cells were cultured in DMEM medium. Purchased from Lifetechnologies TM The solution contains 10% FBS (fetal bovine serum). Purchased from Lifetechnologies TM ), 1% L-glutamine (200mM; Purchased from Lifetechnologies TM ), 1% sodium pyruvate (100mM); Purchased from Lifetechnologies TM ), and 1% streptomycin-penicillin (10,000 U / mL penicillin & 10,000 μg / mL streptomycin); Purchased from Life Technologies TM The cells were incubated at 37°C and 5% CO2. Cell viability was determined by trypan blue rejection assay.

[0057] Preparation of algal proteoglycan extract

[0058] Spirulina dry powder 3 kg was washed with 3 liters of water, suction filtered, 30 liters of water was added to the residue and stirred, heated at 88°C for 1 hour, after cooling, separated by filtration under reduced pressure, the filtrate was adjusted to pH 3.8 with hydrochloric acid, left overnight, centrifuged, the supernatant was adjusted to pH 7 with Na2CO3 solution, then spray dried to obtain 0.599 kg of algal proteoglycan extract, the content of proteoglycan in the extract was determined to be 72.3%.

[0059] The algal proteoglycan extract was weighed under sterile conditions and dissolved in PBS at 50 mg / ml to obtain a stock solution. After centrifugation at 2500 g for 30 minutes, the supernatant was filtered with a 0.2 μm filter. The solution was diluted in the culture medium to treat the cells in the MTS assay experiment. In the following text of the present application, the algal proteoglycan extract is also referred to as "extract K".

[0060] MTS assay

[0061] CellTiter 96® AQueous Non-Radioactive Cell Proliferation Assay Kit (MTS, Promega) was used to measure cell proliferation, based on a colorimetric method to determine the number of viable proliferating cells. The assay kit consists of tetrazolium salt (3-(4,5-dimethylthiazol-2-yl)-5-(3- carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium), MTS) and an electron coupling reagent (phenazine methosulfate, PMS) that increases the stability of the MTS chemistry. MTS is reduced by dehydrogenases in metabolically active cells to a colored product, formazan, which is soluble in the culture medium. After incubation at 37°C for 2 hours, the amount of formazan product is determined by measuring the absorbance at 490 nm, which is directly proportional to the number of viable cells in the culture medium. Finally, the half maximal inhibitory concentration (IC50) of the algal proteoglycan extract was determined on the PANC-1 cell model. All cell culture conditions were repeated three times.

[0062] On day 1, cells were seeded in 96-well culture plates (Microtest

[0063] Falcon) at 1500 cells per well in 100 μl of culture medium, then the cells were treated according to a predetermined concentration range. Specifically, the algal proteoglycan extract was set at 10 different concentrations, with three replicates for each concentration. Cell-free wells without the addition of algal proteoglycan extract were used as control wells.

[0064] ​Before adding the MTS solution, the treated or untreated cell medium was removed to avoid interference of the alginate proteoglycan extract on the MTS assay. 100 μl of medium was added to each well. Then, 20 μl of MTS solution was added to each well and after 4 hours of incubation at 37°C, 5% CO2, the absorbance at 490 nm was measured. The cell medium with or without alginate proteoglycan extract was changed on day 2 and day 4. The absorbance at 490 nm was measured on days 0 (D0), 1 (D1), 2 (D2), 3 (D3), 4 (D4) and 6 (D6) corresponding to the results of the global analysis of 6 x 96 well plates (one day once), as shown in Figure 1. Figure 1

[0065] Results of the cell proliferation assay on the PANC-1 cell line

[0066] MTS results at D0

[0067] The OD values at D0 were measured to verify that the cell seeding of the day before was appropriate and that the protocol applied was working on this cell line. Table 2 below shows the OD values at day 0. We can see that there is no significant statistical difference between the OD values of the groups, which means that the cell seeding was appropriate and the results are reproducible.

[0068] Table 2

[0069]

[0070] Antiproliferative effect of fucoidan extract on PANC-1 cell line

[0071] The OD values corresponding to the different concentrations of alginate proteoglycan extract are shown in Table 3.

[0072] Table 3

[0073]

[0074] After calculation, the percentage of proliferating cells relative to the control (without alginate proteoglycan extract) was determined. The percentage of proliferation of PANC-1 cells relative to the control after treatment with different concentrations of alginate proteoglycan extract each day is shown in Table 4 and Figure 2. Table 5 shows the percentage of inhibition of PANC-1 cell proliferation by the alginate proteoglycan extract. The inhibition rate was calculated by comparing the cell survival after treatment with extract K to the cell survival without treatment. Figure 2

[0075] Table 4

[0076]

[0077] Table 5

[0078] ​​

[0079] As can be seen from Table 5, after treatment with 1.75 mg / ml, 2.5 mg / ml, 3.5 mg / ml and 5 mg / ml of extract K, significant anti-PANC-1 cell proliferation effects were detected on day 1, 2, 3, 4 and 6. For example, on day 1, 2.5 mg / ml of extract K achieved 38.15% inhibition of proliferation, and 5 mg / ml of extract K achieved 37.06% inhibition of proliferation; on day 2, 2.5 mg / ml of extract K achieved 75.64% inhibition of proliferation, and 5 mg / ml of extract K achieved 88.29% inhibition of proliferation; on day 4, 1.75 mg / ml, 2.5 mg / ml, 3.5 mg / ml and 5 mg / ml of extract K all achieved more than 90% inhibition of PANC-1 cell proliferation.

[0080] The IC50 of the algal protein polysaccharide extract on day 1 was greater than 5 mg / ml, and the IC50 on day 2 was between 1 mg / ml and 1.75 mg / ml.

[0081] The above results show that the algal protein polysaccharide extract of the present application has a significant inhibitory effect on PANC-1 pancreatic cancer cells.

[0082] Example 1.2 Clinical cases of fucoidan extract treatment of patients with advanced pancreatic cancer

[0083] Patient condition: male, born in 1927, underwent coronary stent implantation in 1996 due to acute myocardial infarction; underwent cardiac pacemaker implantation in 2003 due to bradycardia, and on December 3, 2013, due to fever, ultrasonic examination found a mass in the head of the pancreas; on December 26, 2013, ultrasound-guided percutaneous biopsy of the mass in the head of the pancreas was performed, and the patient was diagnosed with advanced low-differentiated pancreatic cancer; on January 14, 2014, the patient underwent PTCD + biliary stent implantation; on December 15, 2013, the patient began to take the algal protein polysaccharide extract prepared according to Example 1.1 of the present application, 1350 mg / d, which was increased to 2025 mg / d after 20 days; no other treatment.

[0084] Clinically observed efficacy: stable after partial remission (PR), overall survival period was 20 months.

[0085] Figure 3 The CT imaging changes of the patient after taking the algal protein polysaccharide extract prepared according to Example 1.1 of the present application for three months are shown. As can be seen, the arterial phase image shows that the tumor is reduced from 46 x 51 mm to 35 x 46 mm after three months; the venous phase image shows that the density of the central necrotic area of the tumor is significantly reduced. This further confirms that the algal protein polysaccharide extract of the present application can be used to treat pancreatic cancer and has a significant inhibitory effect on advanced pancreatic cancer.

[0086] Pancreatic cancer is a highly malignant digestive tract tumor. The survival time of pancreatic cancer patients who have not received treatment is about 4 months. Patients who have undergone resection can survive for about 16 months. However, due to the low rate of early diagnosis of pancreatic cancer, most patients are found to have developed to the advanced stage, and thus are not suitable for surgical treatment. The current drug treatment cannot effectively prolong the survival time of patients. The inventors summarized the effects of drug treatment reported in the existing literature (Table 6). It can be seen that even if several drugs are combined for treatment, the overall survival time is at most 9 months. However, the advanced pancreatic cancer patient in this example obtained an unexpected overall survival time of 20 months after taking the alginate protein polysaccharide extract. This indicates that the alginate protein polysaccharide extract of the present application has a significantly better treatment effect on pancreatic cancer patients than the current drug treatment, and this effect is unexpected.

[0087] Table 6

[0088]

[0089] Example 2 Therapeutic effect of fucoidan extract on liver cancer

[0090] In this example, the effect of the alginate protein polysaccharide extract of the present application on the median survival time of 11 hepatocellular carcinoma patients was studied.

[0091] Eleven hepatocellular carcinoma patients took the alginate protein polysaccharide extract prepared according to Example 1.1 of the present application, 1080 mg / d, and continued to take the medicine until death or could not take the medicine orally. The survival time of the entire group of patients was 2-43 months, and the median survival time of the 11 hepatocellular carcinoma patients was 15.2 months. The longest follow-up patient had a survival time of 43 months, 4 patients had a survival time of more than 20 months, 8 patients had a survival time of more than 11 months, 9 patients had a survival time of more than 6 months, and 1 patient had a survival time of less than 3 months. Among these cases, there was one special poor case recommended by the Anhui Charity Association, ZBFU from Anhui Hospital, who was diagnosed with primary liver cancer on August 2, 2005, T2N0M0, stage II, right lobe of liver occupying lesion 3.0*3.7; due to splenomegaly, cirrhosis, and left kidney considering stone bleeding, no other treatment was received, and on September 24, 2005, the patient took the alginate protein polysaccharide extract prepared according to Example 1.1. ZBFU died on April 6, 2009. The patient had a continuous survival time of 43 months.

[0092] Survival of liver cancer patients has been the most intractable problem in the treatment of liver cancer. Chemotherapy of various methods for patients who cannot be operated on can only extend the median survival by 1 to 2 months. The standard drug for treating liver cancer at present is Sorafenib (Multigene, trade name: Multigene), and the median survival of the treatment group and the placebo control group is 10.7 months and 7.9 months, respectively. The median survival of the liver cancer patients in the present embodiment after taking the alginate protein polysaccharide extract is 15.2 months. This shows that the treatment effect of the alginate protein polysaccharide extract of the present application on liver cancer patients is significantly better than the current drug treatment.

[0093] Example 3 Therapeutic effect of fucoidan extract on colon cancer

[0094] In the present embodiment, the treatment effect of the alginate protein polysaccharide extract of the present application on 8 cases of colon cancer patients was studied.

[0095] Among the 8 cases of colon cancer patients, 2 were male and 6 were female, aged 38-68 years, with a median age of 60.5 years; physical condition 70-90; 2 cases of clinical stage III tumor patients were enrolled, 6 cases of clinical stage IV tumor patients were enrolled; III, IV patients accounted for 100%; a total of 8 cases of pathological diagnosis (8 cases of surgery).

[0096] Basic situation of colon cancer subjects

[0097]

[0098] The 8 cases of colon cancer patients took the alginate protein polysaccharide extract prepared according to Example 1.1, 1080 mg / d, and after 56 days of taking, 1 case of partial remission (PR) was observed, 3 cases of stable disease (SD), and 4 cases of disease progression (PD). The effective rate (CR+PR / total number) of the treatment of the 8 cases of colon cancer patients was 12.5%, and the disease control rate (CR+PR+SD / total number) was 50%.

[0099] Example 4 Therapeutic effect of fucoidan extract on gastric cancer

[0100] The applicant also studied the treatment effect of the alginate protein polysaccharide extract of the present application on gastric cancer patients.

[0101] Among the 3 cases of gastric cancer, the gender was male, the age range was 57-67 years, and the median age was 65 years. All 3 cases were advanced patients, 2 cases of clinical stage III tumor patients were enrolled; 1 case of clinical stage IV tumor patient was enrolled, and the gastric cancer tissue type was all adenocarcinoma. A total of 3 cases of pathological diagnosis (including 1 case of biopsy and 2 cases of surgery).

[0102] 3 patients with gastric cancer were administered the alginate polysaccharide extract prepared according to Example 1.1, 1080 mg / d, after 56 days of administration, 2 patients were stable (SD), 1 patient was progressive (PD), and the disease control rate was 66.7%

[0103] Example 5 Therapeutic effect of fucoidan extract on lymphoma

[0104] In this example, the therapeutic effect of the alginate polysaccharide extract of the present application on patients with lymphoma was studied.

[0105] Patient condition: a 62-year-old female diagnosed with non-Hodgkin's lymphoma (diffuse large B), stage IVB (end-stage tumor patient); underwent 6 courses of CHOP chemotherapy, 8 courses of IMVP-16 chemotherapy, and 2 courses of HDAra-c + VP-16 chemotherapy, and a mass appeared under the left jaw, measuring 3 x 2 cm.

[0106] The non-Hodgkin's diffuse large B lymphoma patient who relapsed after multiple chemotherapies began to take the alginate polysaccharide extract prepared according to Example 1.1 of the present application on March 2, 2003, 2700 mg / d, taken orally 3 times a day, and until March 31, 2003, it was found that the lesion was smaller than before, measuring 1.5 x 1.8 cm. The clinical efficacy evaluation was partial remission (PR).

[0107] The non-Hodgkin's diffuse large B lymphoma patient who relapsed after multiple chemotherapies achieved partial remission after 28 days of treatment with the alginate polysaccharide extract, which indicates that the alginate polysaccharide extract of the present application has obvious therapeutic efficacy on lymphoma.

[0108] Example 6 Therapeutic effect of fucoidan extract on esophageal cancer

[0109] In this example, the therapeutic effect of the alginate polysaccharide extract of the present application on patients with esophageal cancer was studied.

[0110] The physical condition of the 2 patients with esophageal cancer enrolled was 80 points, and both were advanced stage (stage III, IV) patients with distant metastasis. After the patients were administered the alginate polysaccharide extract prepared according to Example 1.1, 1 patient achieved partial remission (PR), and 1 patient was stable (SD). The results are shown in the table below.

[0111] Esophageal cancer patients can be evaluated for tumor evaluation

[0112] Number Name abbreviation Center number Tumor stage Histological type Efficacy 1 SXFA 3 IV Adenocarcinoma SD 2 ZSCA 2 IV Squamous carcinoma PR

[0113] Next, the conditions of the two patients will be described in detail.

[0114] Patient SXFA, male, born on March 19, 1941, his condition and treatment are as follows:

[0115] On November 10, 2005, a biopsy confirmed the presence of a low- grade adenocarcinoma in the esophagus, stage IV.

[0116] On November 8, 2005, CT showed a 6 cm nodular protrusion in the mucosa at 40 mm from the dentate line, with erosion and bleeding.

[0117] From August 13, 2006 to November 15, 2006, the patient continued to take the alginate proteoglycan extract prepared according to Example 1.1 of the present application at a dose of 1080 mg / day. Prior to and during the period of taking the alginate proteoglycan extract, the patient did not receive any other treatment.

[0118] On October 13, 2006, CT showed an irregular filling defect 5 cm in size in the lower esophagus, with a lesion height of 5 mm. The efficacy evaluation was stable (SD).

[0119] Patient ZSCA, male, born on July 17, 1957, had the following condition and treatment:

[0120] On May 15, 2006, a biopsy of the puncture smear confirmed the presence of a squamous cell carcinoma in the esophagus, stage IV.

[0121] On May 17, 2006, CT showed a right clavicular lymph node 5.5 x 5 cm in size.

[0122] From May 17, 2006 to November 1, 2006, the patient continued to take the alginate proteoglycan extract prepared according to Example 1.1 of the present application at a dose of 1080 mg / day. Prior to and during the period of taking the alginate proteoglycan extract, the patient did not receive any other treatment.

[0123] On November 1, 2006, CT showed a right clavicular lymph node 2.5 x 2 cm in size. The efficacy evaluation was partial remission (PR).

[0124] The above data show that the alginate proteoglycan extract of the present application also has a therapeutic effect on esophageal cancer.

[0125] Example 7 Fucoidan extract alleviates tumor-related pain

[0126] Example 7.1 Therapeutic effect of fucoidan extract on liver cancer pain

[0127] Pain is a common clinical symptom of advanced liver cancer, which greatly affects the quality of life of the patient and needs to be routinely controlled using strong analgesic drugs. In this example, the inhibitory or preventive effect of the alginate proteoglycan extract on pain was studied in 18 patients with hepatocellular carcinoma.

[0128] 18 patients with hepatocellular carcinoma were administered the alginate proteoglycan extract prepared according to Example 1.1 at a dose of 1080 mg / d, continuously until death or inability to orally administer the drug. None of the patients administered other analgesic drugs during the study, and 14 of the patients were evaluated using a pain scale. Of these 14 patients: 2 patients never experienced pain; 7 patients experienced pain relief; and 5 patients maintained a mild pain of 1-2 degrees without change. The typical cases included the following patients:

[0129] One patient was administered strong morphine analgesics at the time of enrollment, and discontinued the analgesics shortly after receiving the alginate proteoglycan extract; another patient had a large tumor (8 x 8.5 cm) that was detected by imaging, and did not experience pain after receiving the alginate proteoglycan extract.

[0130] The above data show that the alginate proteoglycan extract of the present application has a significant inhibitory and improving effect on pain.

[0131] The evaluation scale used to evaluate pain is as follows:

[0132] Quality of life scores for patients with tumors

[0133]

[0134] Example 7.2 Therapeutic effect of fucoidan extract on pancreatic cancer pain

[0135] The applicant also studied the inhibitory effect of the alginate proteoglycan extract on pain in 24 patients with pancreatic cancer who had pain symptoms. The 24 patients with pancreatic cancer enrolled were administered the alginate proteoglycan extract prepared according to Example 1.1 at a dose of 2025 mg / d, continuously until death or inability to orally administer the drug. The pain symptoms of the 24 patients were significantly alleviated, as evaluated by the pain scale.

[0136] Example 8 Inhibitory effect of fucoidan extract on inflammation

[0137] Tumor-promoting inflammation is considered to be one of the characteristics that promote cancer. Chronic inflammatory diseases can increase the risk of developing certain cancers, and a lot of epidemiological evidence shows that non-steroidal anti-inflammatory drugs, especially aspirin, are powerful chemopreventive agents. There are many different inflammatory cells in the tumor microenvironment; targeting these factors in genetic, transplantable, and induced mouse cancer models can significantly reduce the incidence, development, and spread of tumor diseases. Therefore, this complex inflammatory network provides a target for the prevention and treatment of malignant diseases. This example studies the effect of the alginate proteoglycan extract on the expression of inflammatory mediators in cancer cells.

[0138] 8.1 Regulatory effect of fucoidan extract on expression of inflammatory mediators in a pancreatic cancer model

[0139] Algal polysaccharide extract was prepared and the PANC-1 pancreatic cancer cell line was cultured according to the scheme described in Example 1.

[0140] On day 1, cells were seeded in 100 mm culture dishes. On day 2, PANC-1 cells were treated with either 5 mg / ml algal proteoglycan extract or PBS-containing medium (control) on day 3 (each culture dish contained 16 ml of culture medium). Cells were divided into three groups: control group, 3-hour treatment group, and 18-hour treatment group, with each group treated twice.

[0141] use The company The system investigated six qPCR signaling pathways. Expression of relevant factors: including angiogenesis, inflammation, interferon & immune system, cytokines, oxidative stress, and the HLA system. Table 7 below lists the number of factors among the 76 inflammatory mediators detected that were significantly downregulated (at least 1-fold) compared to the control sample. Table 8 lists the folds of downregulation of some exemplary factors compared to the control.

[0142] Table 7

[0143]

[0144]

[0145] Table 8

[0146]

[0147] The results above show that the algal polysaccharide extract of this application can regulate the expression of various inflammatory mediators and cytokines in PANC-1 pancreatic cancer cells and has a significant inhibitory effect on the expression of various inflammatory factors.

[0148] 8.2 Regulatory effect of fucoidan extract on expression of inflammatory mediators in a liver cancer and lung cancer model

[0149] In this study, the HuH7 hepatocellular carcinoma cell line and the A549 lung adenocarcinoma cell line were used. These two cell lines were developed from... Company-sponsored training.

[0150] HuH7 cells were cultured in DMEM medium supplemented with 10% FBS (fetal bovine serum). Purchased from Lifetechnologies TM ), 1% L-glutamine (200mM; Purchased from Life Technologies TM ), 1% sodium pyruvate (100mM); from Life technologies TM ), and 1% streptomycin-penicillin (10,000 U / mL penicillin & 10,000 pg / mL streptomycin; from Life technologies TM ) and incubated at 37 °C, 5% CO2. Cell viability was determined by trypan blue exclusion test.

[0151] A549 cells were cultured in RPMI medium supplemented with 10% FBS (fetal bovine serum, from Life technologies TM ), 1% L-glutamine (200 mM; from Life technologies TM ), 1% sodium pyruvate (100 mM; from Life technologies TM ), and 1% streptomycin-penicillin (10,000 U / mL penicillin & 10,000 pg / mL streptomycin; from Life technologies TM ) and incubated at 37 °C, 5% CO2. Cell viability was determined by trypan blue exclusion test.

[0152] Algal glycoprotein polysaccharide extract was prepared according to the protocol described in Example 1. The expression of relevant factors was detected according to the method in Example 3.1. The number of inflammatory mediators and cytokines detected in A549 cells and in HuH7 cells and the number of factors whose expression was significantly down-regulated (at least 2-fold or more) compared to control samples after 6 hours or 12 hours of treatment are listed in Table 9. The down-regulation fold of some exemplary factors is also listed in Table 10.

[0153] Table 9

[0154]

[0155] Table 10

[0156]

[0157]

[0158] The results in Examples 8.1 and 8.2 show that the algal glycoprotein polysaccharide extract of the present application is a major modulator of the expression of inflammatory mediators and cytokines in various cancer models, and can significantly inhibit the expression of various pro-inflammatory factors, which confirms that the algal glycoprotein polysaccharide extract of the present application can inhibit the occurrence and development of inflammation, especially tumor-related inflammation.

[0159] In addition, Table 11 below lists the correspondence between inflammatory factors and the diseases mediated thereby, from which it can be seen that the inflammatory mediators and cytokines modulated by the algal proteoglycan extract of the present application are capable of mediating the occurrence and development of a variety of diseases. Thus, the algal proteoglycan extract capable of down-regulating these inflammatory factors can be used to treat or prevent a variety of diseases and conditions associated with the inflammatory factors, including but not limited to the diseases or conditions listed in the table below.

[0160] Table 11

[0161]

[0162]

[0163]

[0164]

[0165]

[0166] Example 9 Synergistic effect of fucoidan extract combined with chemotherapy drugs in the treatment of cancer

[0167] The experimental animals used in this study were female C57 mice of 18-22 g or female KM mice of 18-22 g, both of which were provided by the Shanghai Experimental Animal Center of the Chinese Academy of Sciences, and the qualification certificate number was: Chinese Academy No. 005.

[0168] The tumor species included B-16 melanoma and S-180 sarcoma, which were provided by the Shanghai Institute of Materia Medica of the Chinese Academy of Sciences.

[0169] Carboplatin was purchased from Shandong Qilu Pharmaceutical Factory, doxorubicin was purchased from China Zhejiang Haimen Pharmaceutical Factory, etoposide was purchased from Shanghai Medical Industry Research Institute Yadaon Pharmaceutical Company Pudong Pharmaceutical Factory, 5-fluorouracil was purchased from Shanghai Xudong Haipu Pharmaceutical Co., Ltd., cyclophosphamide was purchased from Shanghai Hualian Pharmaceutical Co., Ltd., and the rest of the chemotherapeutic drugs used were purchased from Beijing Kuer Biological Engineering Co., Ltd.

[0170] Example 9.1 Therapeutic effect of fucoidan extract combined with other chemotherapy drugs on melanoma

[0171] Experimental protocol

[0172] 18-22 g female C57 mice and well-grown 7-11 day old B-16 melanoma species were used. The tumor tissue was prepared into a cell suspension and inoculated subcutaneously in the right axillary of the mice at about 4.5-5 x 10 6Cell / only. After 24 hours of inoculation, the mice were randomly grouped and put into different cages (n=6). Alginate oral administration, carboplatin, doxorubicin or CTX intraperitoneal administration, once a day, different doses of continuous administration for seven days from the next day. The blank control group was given normal saline (NS). The animals were sacrificed 24 hours after drug withdrawal, and the body weight was measured. The tumors were removed and weighed, the average tumor weight of each group was calculated, the tumor inhibition rate was calculated according to the following formula and T test was performed.

[0173]

[0174] Wherein A is the average tumor weight of the blank control group (g), B is the average tumor weight of the treatment group (g).

[0175] Dose of administration

[0176] According to the results of the pre-experiment, the dose of alginate polysaccharide extract (hereinafter referred to as alginate polysaccharide) is set to 30 mg / kg and 60 mg / kg, the dose of carboplatin is 4 mg / kg and 8 mg / kg, the dose of doxorubicin is 1 mg / kg, and the dose of CTX is 7.5 mg / kg.

[0177] Results of the experiment

[0178] Table 12 Treatment effect of alginate polysaccharide (30 mg / kg) combined with carboplatin on melanoma

[0179]

[0180] Table 13 Treatment effect of alginate polysaccharide (60 mg / kg) combined with carboplatin on melanoma

[0181]

[0182] Table 14 Treatment effect of alginate polysaccharide combined with doxorubicin on melanoma

[0183]

[0184] The above results show that the anti-tumor effect of alginate polysaccharide combined with carboplatin or doxorubicin is significantly enhanced compared with single drug, and the toxicity to mice is not increased. For example, alginate polysaccharide (30 mg / kg) combined with carboplatin significantly increases the inhibition rate of carboplatin (38.9%, P<0.01); alginate polysaccharide (30 mg / kg) combined with doxorubicin also significantly increases the inhibition rate of doxorubicin (13.1%).

[0185] The above results show that the alginate polysaccharide extract of the present application can enhance the therapeutic effect of carboplatin, doxorubicin and other chemotherapeutic drugs on B-16 melanoma transplanted tumors in mice, which confirms that the alginate polysaccharide extract has a synergistic effect with clinically commonly used chemotherapeutic drugs in the treatment of melanoma.

[0186] Example 9.2 Therapeutic effect of fucoidan extract combined with other chemotherapy drugs on S-180 sarcoma in mice

[0187] Experimental scheme

[0188] Eighteen to twenty-two gram female KM mice and well-grown S-180 tumor species of 7-11 days were used. The tumor tissue was prepared into a cell suspension and inoculated subcutaneously in the right axillary of the mice, about 4.5-5 x 10 6 cells per mouse. After 24 hours, the mice were randomly divided into groups and placed in different cages (n=6). Alginate polysaccharide extract (hereinafter referred to as alginate polysaccharide) was administered orally, and cyclophosphamide, carboplatin, 5-fluorouracil and etoposide were administered intraperitoneally, once a day, starting the next day for seven consecutive days at different doses. The blank control group was given normal saline (NS). The animals were sacrificed 24 hours after drug withdrawal, and the body weight (g) was measured. The tumor was cut off and weighed (g), and the average tumor weight of each group was calculated. The tumor inhibition rate was calculated according to the following formula and T test was performed.

[0189]

[0190] Wherein A is the average tumor weight of the blank control group (g), and B is the average tumor weight of the treatment group (g)

[0191] Experimental results

[0192] Table 15 Therapeutic effect of alginate polysaccharide combined with cyclophosphamide on S-180 sarcoma in mice

[0193]

[0194]

[0195] Table 16 Therapeutic effect of alginate polysaccharide combined with carboplatin on S-180 sarcoma in mice

[0196]

[0197] Table 17 Therapeutic effect of alginate polysaccharide combined with etoposide on S-180 sarcoma in mice

[0198]

[0199] Table 18 Therapeutic effect of alginate polysaccharide combined with 5-fluorouracil on S-180 sarcoma in mice

[0200]

[0201] From the data in Tables 15-18, it can be seen that alginate polysaccharide at a dose of 20-30 mg / kg had no inhibitory effect on the growth of S-180 sarcoma (P>0.05), and alginate polysaccharide at a dose of 60 mg / kg had an inhibitory effect of 35.4% on the growth of S-180 sarcoma, showing a certain inhibitory effect on the growth of sarcoma in mice.

[0202] Carboplatin at a dose of 4 mg / kg had no inhibitory effect on the growth of S-180 sarcoma in mice (P>0.05), and when combined with alginate polysaccharide at a dose of 20 mg / kg, the inhibitory rate reached 33%. When alginate polysaccharide at a dose of 60 mg / kg was combined with cyclophosphamide at a dose of 7.5 mg / kg, the inhibitory rate on the growth of S-180 sarcoma was 52.6%, which was more than 10% higher than that of cyclophosphamide alone.

[0203] Etoposide at a dose of 3 mg / kg had an inhibitory effect of 26.9% on the growth of S-180 sarcoma in mice (P>0.05), and when combined with alginate polysaccharide at a dose of 20 and 30 mg / kg, the anti-tumor effect was enhanced compared with that of etoposide alone, and the inhibitory rates were 33.5% (P<0.05) and 35.7% (P<0.01), respectively.

[0204] 5-Fluorouracil at a dose of 15 mg / kg had a weak inhibitory effect on the growth of S-180 sarcoma in mice, and when combined with alginate polysaccharide, the anti-tumor effect was significantly enhanced, with an inhibitory rate of 67.5%, which indicated that the two drugs had a synergistic effect.

[0205] The above data show that the alginate polysaccharide extract of the present application, when combined with 5-fluorouracil, etoposide, carboplatin, or cyclophosphamide, can increase the therapeutic effect of these drugs on S-180 sarcoma in mice, and the synergistic effect is more obvious when alginate polysaccharide is combined with 5-fluorouracil.

[0206] In addition, the applicants also studied the inhibitory effect of the algal proteoglycan extract alone and the algal proteoglycan extract in combination with gemcitabine on tumors in nude mice with pancreatic cancer, and the inhibitory effect on pancreatic cancer in a human tumor xenograft (PDX) model. The results showed that the algal proteoglycan extract of the present application in combination with gemcitabine also has a synergistic effect on the treatment of pancreatic cancer.

[0207] It can be understood that although the applications involved are described above in the specific forms, the applications are not limited to the specific contents described in the specific forms. It is obvious to those skilled in the art that various equivalent changes can be made to the technical features involved in the applications without departing from the spirit of the applications described herein, and these changes should all belong to the scope of the applications.

Claims

1. Use of a pharmaceutical composition comprising an algal proteoglycan extract and one or more other antitumor drugs in the preparation of a medicament for the treatment or prevention of sarcoma, wherein said antitumor drug is 5-fluorouracil (5-FU) or carboplatin; and The algal proteoglycan extract is obtained through the following steps: a. Dissolve the dry powder of blue-green algae in 5-20 times its volume of water to break down the cell walls. b. Heat the mixture obtained in step a at 60-100℃, cool it, and then perform solid-liquid separation. c. Adjust the pH of the liquid obtained in step b to less than 7, and then perform solid-liquid separation. d. Adjust the liquid obtained in step c to neutral, concentrate it, and dry it if necessary.

2. The use as described in claim 1, wherein the antitumor drug is 5-fluorouracil (5-FU).

3. The use as described in claim 1, wherein the antitumor drug is carboplatin.

4. The use as described in claim 1, wherein the algal proteoglycan extract and / or the algal proteoglycan extract are formulated together with a pharmaceutically acceptable carrier into a pharmaceutically acceptable dosage form.

5. The use as described in claim 4, wherein the pharmaceutically acceptable dosage form is an oral liquid, capsule, powder, tablet, granule, pill, syrup, or injection.

6. The use as described in claim 1, wherein the algal proteoglycan extract is administered orally.

7. The use as described in claim 1, wherein the algal polysaccharide extract contains a polysaccharide content greater than 50%, greater than 60%, greater than 65%, greater than 70%, or greater than 75% by weight.

Images