JP5215858B2 - Anti-angiogenic composition containing extract having anti-angiogenic action and lecithin - Google Patents

Description

  The present invention relates to an anti-angiogenic composition containing an extract having an anti-angiogenic action (anti-angiogenic extract) and lecithin. In particular, it relates to an anti-angiogenic composition containing shark meat extract and / or mussel meat extract and lecithin.

  The present invention also relates to a method for treating or preventing a disease or psychosomatic dysfunction effective in suppressing angiogenesis, using the anti-angiogenic composition of the present invention.

Angiogenesis means the proliferation and growth of new blood vessels. Angiogenesis plays an important role in various physiological and pathological conditions.
In healthy bodies, angiogenesis occurs during the proliferative phase of cells in wound healing, to restore blood flow to tissues after injury, and during menstrual periods and pregnancy in women.
In a healthy body, the promotion and suppression of angiogenesis is controlled by switching between “on” and “off”, the “on” switch is an angiogenesis stimulating factor, and the “off” switch is an angiogenesis inhibitor is called.
In a normal healthy body, an angiogenesis factor and an angiogenesis inhibitory factor are balanced in order to control the promotion and suppression of angiogenesis.

  The lack of control of angiogenesis causes many serious diseases. Many diseases caused by so-called “excessive neovascularization” are known. These diseases include arthritis (Non-Patent Documents 1 and 2), retinopathy (Non-Patent Documents 3 and 4), macular degeneration (Non-Patent Documents 5, 6, and 7) and cancer (Non-Patent Documents 8 and 9). )and so on. For example, cancer has high metabolic efficiency compared to normal growth and organs. Thus, because cancer requires more blood to obtain a higher nutrient supply, inhibition of angiogenesis can be a mechanism for inhibiting or controlling tumor growth. Thus, angiogenesis inhibitors can delay the progression of these diseases.

  A number of anti-angiogenic compositions and formulations (Non-Patent Documents 10 and 11) are known, including lipid-based formulations. One of these is derived from various types of shark muscle tissue (Patent Document 1).

  The inventors have found that the combination of this shark meat extract and lecithin enhances the anti-angiogenic effect of the shark meat extract. Such an effect of enhancing the anti-angiogenic action is unexpected from the known properties of lecithin that does not have an anti-angiogenic action.

  Furthermore, we examined whether lecithin can enhance the anti-angiogenic action of other natural product extracts, and discovered that lecithin can also enhance the anti-angiogenic action of mussel meat extract.

  The surprising fact that lecithin enhances the anti-angiogenic action of a wide range of natural product extracts is the basis for this discovery.

Special table 2004-516272 Giatromanolaki et al., Arthritis Research & Therapy, 5: R193-201. DeBusk et al., Athritis & Rheumatism, 48: 2461-71. Bainbridge et al., Clinical Science, 104: 561-75. Umeda et al., Ophthalmic Research, 35: 217-23. Bainbridge et al., Clinical Science, 104: 561-75. Yamaza et al., Journal of Electron Microscopy, 51: 127-31. Ohno-Matsui et al., Journal of Cellular Physiology, 189: 323-33. Sivridis et al., Journal of Pathology, 201: 173-80. Longo et al., Angiogenesis, 5: 237-56. Scappaticci, Expert Opinion on Investigational Drugs, 12: 923-32. Caceres and Gonzalez, Puerto Rico Health Sciences Journal, 22: 149-51.

  The present invention provides an anti-angiogenic composition comprising an anti-angiogenic extract and lecithin, and presents an effective combination of an anti-angiogenic extract and lecithin that exhibits a synergistic effect of anti-angiogenic action. This is the object of the present invention.

First, the present invention provides an anti-angiogenic composition containing an anti-angiogenic extract and lecithin.
As a first embodiment of the present invention, the anti-angiogenic extract is a shark meat extract and / or a mussel meat extract. The mussel extract is preferably an extract of New Zealand green mussel (Perma canaliculus) meat.

It is desirable that the anti-angiogenic extract and the anti-angiogenic composition of lecithin further contain an edible oil such as olive oil. The anti-angiogenic composition preferably contains vitamin E.
The ratio based on the weight of the anti-angiogenic extract and lecithin contained in the anti-angiogenic composition of the anti-angiogenic extract and lecithin may be any weight ratio as long as it provides a synergistic effect. It is desirable that the extract: lecithin is in a weight ratio in the range of 1: 1 to 10: 1. The optimum is 4: 1 to 5: 1.

  Secondly, the present invention provides a method for treating or preventing a disease or disorder in which angiogenesis is beneficial, comprising administering the anti-angiogenic composition described in the first to a mammal. Thus, the antiangiogenic composition described first may be in the form of a medicament.

  In addition, the present invention also provides an anti-angiogenic composition for preventing or treating diseases and disorders considered to be beneficial for inhibiting angiogenesis.

  Diseases and disorders useful for inhibiting angiogenesis of the present invention are arthritis, retinopathy, macular degeneration, and cancer. The target of treatment or prevention is a mammal, for example, a human; a pet such as a dog or a cat; a domestic animal such as a cow, pig or chicken, and is particularly preferably a human.

  The present invention also provides the use of an anti-angiogenic composition for the manufacture of a medicament for preventing or treating diseases and disorders for which it is thought beneficial to suppress angiogenesis.

  Surprisingly, the inventor found that a mixture of anti-angiogenic extracts such as shark meat extract and mussel meat extract and lecithin significantly enhanced anti-angiogenic activity compared to lecithin-free extracts. I found out to do.

  Therefore, by combining an extract having an anti-angiogenic action obtained from a natural product with lecithin, the anti-angiogenic action of the extract can be enhanced more than when it is used alone. In particular, a shark meat extract having an anti-angiogenic action and / or a combination of mussel extract and lecithin can enhance the anti-angiogenic action of these extracts compared to when used alone.

  The present invention provides an anti-angiogenic composition comprising an anti-angiogenic extract and lecithin. In particular, it relates to an anti-angiogenic composition containing shark meat extract and / or mussel meat extract and lecithin.

  The term “anti-angiogenic extract” in the present invention means an extract having an anti-angiogenic action obtained from a natural product, for example, an extract obtained from shark meat or an extract obtained from mussel meat. And extracts obtained from fungus bodies of mushrooms (for example, extracts obtained from Phellinus Linteus and Grifola frondosa reported to have anti-angiogenic activity in WO / 2006/009477). Here, the natural product means organisms such as animals, plants, and microorganisms, and the natural product may be processed or unprocessed. The anti-angiogenic effect means an angiogenesis inhibitory action, that is, an action that inhibits or suppresses proliferation and growth of new blood vessels.

  The term “extract” in the present invention means a solvent fraction after mixing a solid and / or liquid natural product with a specific solvent or a substance after removing the solvent from the solvent fraction. The extract may be fractionated and isolated by ordinary methods such as chromatography and filtration.

  Extraction methods include, but are not necessarily limited to, solvent extraction methods. Any suitable solvent may be used. The solvent may be an organic solvent, an aqueous solvent, or a mixed solvent thereof. Ethanol is a typical organic solvent (or aqueous ethanol mixed solvent), but other organic solvents (for example, methanol, ethyl acetate, dichloromethane, or a mixed solvent thereof) may be used. . In addition, a supercritical fluid such as supercritical carbon dioxide can be used as the extraction solvent.

The term “shark meat extract” in the present invention means an extract obtained from shark meat using the above-mentioned solvent. In particular, it means the shark meat extract disclosed in Patent Document 1. The term “shark meat” as used herein refers to all fish meat parts including edible parts, but in order to avoid misunderstanding, the internal organs parts are not included.
The shark meat extract of the present invention is generally an oily substance, such as an oil or paste, at ambient temperatures that generally range from about 15 ° C to 25 ° C.

  It has been found that the main component of this shark meat extract is a phospholipid such as phosphatidylethanolamine (PE) and phosphatidylcholine (PC) (Patent Document 1). The phospholipid content is usually in the range of 20-40% by weight. Furthermore, it usually contains phospholipid fatty acids such as docosahexaenoic acid (DHA), arachidonic acid (AA), eicosapentaenoic acid (EPA) and the like. Compared to other fish extracts or products, shark meat extract contains a high concentration (20-35% by weight) of DHA relative to total fatty acids. DHA samples are known to be potent inhibitors of angiogenesis (Patent Document 1). Since the DHA concentration in the shark meat extract is high, it is presumed that DHA is a component that plays a part in the ability of this extract to suppress angiogenesis. The shark meat extract is also clearly different from other fish extracts and products in that the triglyceride concentration is low (less than 10% by weight).

  A typical extraction method involves mincing meat pieces from one or more sharks using a blender, freeze drying (or air drying), and then mixing with a solvent such as ethanol. Usually, the mixture is stirred at room temperature for 1 to 24 hours. The solvent is then separated from the meat pieces by filtration. Mixing of meat pieces and solvent is optional but repeated. The solvent is then removed by evaporation and the shark meat extract is obtained as an oil or oil. This oil or oily substance usually contains various free fatty acids and glycerol-bound fatty acids.

  The term “shark meat” in the present invention is not limited to those described here, but rig (lemonfish; scientific name: Mustelus lenticulatus), school shark (scientific name: Galeorhinus galeus), ghost shark (Ghost Shark) Scientific name: Hydrolagus sp), Mako; Scientific name: Isurus oxyrinchus, Blue shark; Scientific name: Prionace glauca, Elephant fish; Scientific name: Callorhynchus milii, Salmon shark; Scientific name: L, It means the meat of various sharks or shark-like organisms, including blacktip reef shark (scientific name: Carcharhinus melanopterus), and horned shark (spiny dogfish; scientific name: Squalus acanthias). Preferred is blue shark (scientific name: Prionace glauca), and more preferred is spiny dogfish (scientific name: Squalus acanthias).

The term “mussel meat extract” in the present invention means an extract obtained from mussel meat using the above-mentioned solvent. The “mussel meat” mentioned here refers to all shellfish parts including edible parts, and also includes internal organs parts. The mussel extract of the present invention is generally an oily substance, such as an oil or paste, at ambient temperatures that generally range from about 15 ° C to 25 ° C.
This mussel extract contains lipids such as long chain ω3 fatty acids (especially EPA and DHA), phospholipids and various marine sterols.

  A typical extraction method is to use a blender to shred meat pieces from one or more mussels, freeze freeze (or air dry) and then mix with a solvent such as ethanol. Usually, the mixture is stirred at room temperature for 1 to 24 hours. The solvent is then separated from the meat pieces by filtration. Mixing of meat pieces and solvent is optional but repeated. The solvent is then removed by evaporation and the mussel extract is obtained as an oil or oil.

  The term “mussel meat extract” in the present invention is not limited to those described here, but extracts from various mussel meats including green mussel (Perna canaliculus) and purple mussel (Mytilus edulis). means.

  The term “lecithin” in the present invention means a lipid composition containing phospholipid, and may be a commercially available lipid product or composition. Preferably, phosphatidylcholine is contained as a phospholipid in an amount of 10 to 100% by weight, preferably 20 to 90% by weight, more preferably 25 to 90% by weight based on the total lipid. The origin of the lipid constituting lecithin is not particularly limited unless it is derived from shark meat or mussel meat, and may be derived from plants (eg, soybean, sunflower and rapeseed seeds), animals (eg, chicken egg yolk), or microorganisms. May be. Preferably, it is derived from soybean and egg yolk. For example, soy lecithin means a lipid composition comprising phosphatidylcholine produced from soybeans. Egg yolk lecithin means a lipid composition containing phosphatidylcholine produced from chicken egg yolk. Soybean lecithin and egg yolk lecithin may be commercially available or prepared by themselves.

  The “anti-angiogenic composition” in the present invention includes an extract having an anti-angiogenic action obtained from a natural product and lecithin, thereby preventing an anti-angiogenic action from being used alone. It means a composition having an anti-angiogenic action with enhanced angiogenic action.

  The anti-angiogenic composition of the present invention can be used as it is, or can be mixed with edible oil and encapsulated for oral administration. It is also possible that the anti-angiogenic composition is mixed with a solid carrier such as cyclodextrin to form a tablet, granule, powder or the like. The granules, powders, and similar shapes may be included or mixed with other substances such as food for oral administration. It is also conceivable that the anti-angiogenic composition can be dissolved in a solvent corresponding to injection. In addition, the addition of ingredients such as vitamin E may also be included in the formulation.

  Edible oils include olive oil, sesame oil, cottonseed oil, peanut oil, palm oil, rapeseed oil, corn oil, linseed oil, wheat germ oil, soybean oil, castor oil, rice oil, almond oil, cocoa butter, coconut oil, poppy seed Oil, sunflower oil and tea seed oil. These may be used alone or in combination. These edible oils may be commercially available or prepared by themselves. Preferably, it is olive oil.

  Olive oil means oil extracted from crushed or squeezed olive fruit. Similarly, sesame oil, cottonseed oil, peanut oil, palm oil, rapeseed oil, corn oil, linseed oil, wheat germ oil, soybean oil, castor oil, rice oil, almond oil, cocoa butter, coconut oil, poppy seed oil, sunflower oil And tea seed oil means oil extracted by grinding or pressing each seed and fruit.

  Vitamin E means α-, β-, γ-, δ-tocopherol and α-, β-, γ-, δ-tocotrienol, and is used for antioxidant purposes.

  The anti-angiogenic composition of the present invention may further contain sweeteners, colorants, flavors, antioxidants, and / or preservatives well known to those skilled in the art.

  In the anti-angiogenic composition of the present invention, the total content of the extract having anti-angiogenic activity and lecithin is, for example, 0.1 to 99.9% by weight, preferably 1 to 99%. . The remaining part is edible oil, sweetener, colorant, flavor, antioxidant, and / or preservative.

  Angiogenesis is involved in a wide range of diseases and disorders. Therefore, the anti-angiogenic composition of the present invention is useful for the treatment and prevention of such diseases and disorders. Diseases and disorders associated with angiogenesis include, but are not limited to, cancer, retinopathy, macular degeneration, psoriasis and arthritis.

  Therefore, the “disease or disorder in which it is beneficial to suppress angiogenesis” in the present invention refers to a disease in which progression of the disease or disorder is suppressed, or symptoms are improved or reduced by inhibiting angiogenesis. Or it means a disorder, for example, cancer, retinopathy, macular degeneration, psoriasis and arthritis.

  “Treatment” in the present invention means to suppress the progression of a disease or disorder that has already developed, or to improve or reduce symptoms. Also, “prevention” means preventing or delaying the onset of a disease or disorder.

Arthritis means, for example, osteoarthritis, temporomandibular disorder and rheumatoid arthritis. Preferably, it means rheumatoid arthritis with synovitis.
Retinopathy means, for example, diabetic retinopathy and hypertensive retinopathy.
Macular degeneration means, for example, age-related macular degeneration. Preferably, it means wet type age-related macular degeneration.
Cancer means a malignant tumor, such as lung cancer, breast cancer, stomach cancer, colon cancer, uterine cancer, ovarian cancer, laryngeal cancer, pharyngeal cancer, tongue cancer, osteosarcoma, chondrosarcoma, rhabdomyosarcoma, leiomyosarcoma , Fibrosarcoma, liposarcoma, angiosarcoma, leukemia, malignant lymphoma, myeloma and the like. Preferred are skin cancer such as melanoma and breast cancer.

  The anti-angiogenic composition of the present invention can be used for the manufacture of a medicament for the treatment or prevention of these diseases or disorders. The medicament containing the anti-angiogenic composition comprises the anti-angiogenic composition of the present invention, cream, sublingual agent, massa oil, solution, suspension, lotion, ointment, gel, tablet, capsule, granule, powder, Oral administration, transdermal administration, sublingual administration, enteral administration, intramuscular administration, subcutaneous administration, intravenous administration, nasal administration, and ophthalmic administration may be performed as a syrup or suppository. Preferred are cream, sublingual agent, and massa oil. Therefore, the medicament containing the anti-angiogenic composition may further contain pharmaceutically acceptable carriers, adjuvants or additives well known to those skilled in the art.

  Well known pharmaceutically acceptable carriers, adjuvants, or additives include solvents, vegetable oils, mineral oils, fatty oils, liquid paraffins, buffering agents, preservatives, wetting agents, chelating agents, antioxidants, stabilization Agents, emulsifiers, suspending agents, gel-forming agents, ointment bases, suppository bases, penetration enhancers, fragrances, sweeteners, colorants, fragrances and skin protection agents.

  Examples of the solvent include, but are not limited to, water, alcohol, BG (1,3-butylene glycol), polyethylene glycol, propylene glycol, glycerol, liquid polyalkylsiloxane, and mixtures thereof.

Vegetable oils include the edible oils described above.
Buffering agents include, but are not limited to, citric acid, acetic acid, tartaric acid, lactic acid, hydrogen phosphate, diethylamine, and mixtures thereof.
Wetting agents include, but are not limited to, glycerin, propylene glycol, pentylene glycol, sorbitol, lactic acid, urea, BG (1,3-butylene glycol), soy sterol, and mixtures thereof. .

Chelating agents include, but are not limited to sodium EDTA, citric acid and mixtures thereof.
Antioxidants include, but are not limited to, butylated hydroxyanisole (BHA), ascorbic acid and its derivatives, and cysteine and mixtures thereof in addition to vitamin E described above.

  Emulsifiers include natural rubber (eg, acacia gum), tragacanth gum, xanthan gum; natural phosphatide (eg, soy lecithin); sorbitan monooleate; wool oil; wool alcohol; sorbitan ester; monoglyceride; fatty alcohol (eg behenyl alcohol); Fatty acid esters (eg, triglycerides of fatty acids such as glyceryl tri (capryl / capric acid), glyceryl stearate (SE)); and mixtures thereof, but are not limited to these.

  Suspending agents include cellulose and its derivatives (such as carboxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, etc.), carrageenan, acacia gum, gum arabic, tragacanth and mixtures thereof. There is no limit.

  Gel bases and thickening ingredients include liquid paraffin, polyethylene, fatty oil, colloidal silica or aluminum, zinc soap, glycerol, propylene glycol, tragacanth, carboxyvinyl polymer, magnesium silicate-aluminum, hydrophilic polymers (eg starch Cellulose derivatives such as carboxymethylcellulose, hydroxyethylcellulose and other cellulose derivatives), water-swellable hydrocolloids, carrageenan, hyaluronic acid salts (eg hyaluronic acid gels selectively containing sodium chloride), alginate esters (eg propylene alginate) Glycol) and mixtures thereof, but are not limited thereto.

  Ointment base includes beeswax, paraffin, cetanol, cetyl palmitate, cetearyl alcohol, polyglyceryl-10 stearate, stearic acid, PEG-150 stearate, vegetable oil, fatty acid sorbitan ester, polyethylene glycol, fatty acid sorbitan ester and oxidized Examples include, but are not limited to, condensation products with ethylene (for example, polyoxyethylene sorbitan monooleate) and mixtures thereof.

  Hydrophobic ointment bases include, but are not limited to paraffins, vegetable oils, animal fats, synthetic glycerides, waxes, lanolin, liquid polyalkylsiloxanes and mixtures thereof.

The hydrophilic ointment base includes, but is not limited to, solid macrogol (polyethylene glycol).
The composition of the present invention may further contain another drug having an anti-angiogenic action.

  In the anti-angiogenic composition of the present invention, the total content of the extract having anti-angiogenic activity and lecithin is, for example, 0.1 to 99.9% by weight, preferably 1 to 99%. . The remaining part is a conventional carrier, adjuvant, additive or other agent.

  The dose effective for treating or preventing a disease or disorder used in the present invention varies depending on the degree of the disease or disorder and the administration method, and is not limited as long as it is an effective amount for suppressing angiogenesis. The amount of the anti-angiogenic extract is 0.01 mg to 100 mg / kg body weight · day, preferably 0.1 mg to 10 mg / kg body weight · day, more preferably 1.0 mg to 10.0 mg / kg body weight · day. .

  The invention is further illustrated by the following examples. However, it should be understood that the present invention is not limited to the examples shown below.

Anti-angiogenic action of shark meat extract + lecithin Preparation of Blue Shark meat extract Frozen blue shark meat sliced to 2cm thickness, vacuum oven set at 35 ° C and less than 2mbar Put it in. After 24 hours, the piece of meat was taken out and crushed and then returned to the vacuum oven again for 3-4 days. Shark meat weight is usually reduced to the original 20% during the lyophilization process. The freeze-dried meat pieces were further finely ground by hand and then pulverized with a Waring blender to form a mixture of flour and fibers.

  Shark meat powder (900 g) and solvent (99.5 vol% ethanol 4.5 L) were stirred overnight. In order to stir effectively, the solvent: powder ratio had to be 5: 1. The container was shielded from light by covering it with aluminum foil. The mixture was filtered using Schleicher & Schuell 595 filter paper. The filtration residue was stirred overnight with fresh solvent (3 L) and filtered. The filtrates from the two filtrations were mixed and the solvent was removed by rotary evaporation to give a Blue Shark meat extract as an oily substance (yield 13.7%).

  The lecithin used was egg yolk lecithin PL-30S manufactured by Kewpie Corporation. Egg yolk lecithin PL-30S is a lecithin extracted from egg yolk of chicken egg, and its lipid composition is phosphatidylcholine 29.6%, phosphatidylethanolamine 4.8%, sphingomyelin 0.3%, lysophosphatidylcholine 0.4%, Triglyceride 62.1%, cholesterol 2.8%.

Measurement of anti-angiogenic activity Anti-angiogenic activity was measured by aortic ring assay. The experimental method is based on the description of Nicosia and Ottinetti (Lab Invest. 63: 115-122 (1990)) and the description of Brown et al. (Lab Invest. 75: 539-555 (1996)).

After removal of the fat and fibrous tissue surrounding the blood vessels, the aorta of rats (Lewis rat, Charles River Laboratories, Wilmington, MA, USA) was cut into a 2 mm thick ring. Fibrinogen solution 0.4 mL (The fibrinogen solution is 1 mg / ml in 3 mL of 50 mL MCDB131 culture solution (Sigma Cat No. M-8537, Batch 064K8305) in which 150 mg of fibrinogen (Sigma Cat No. F-9754, Batch 041K7604) is dissolved. 10 ml of thrombin (prepared by adding Serva Cat No. 36402. Batch 09309) to a 24-well culture plate (Costar® 24 Well TC-Treated Microplates, Individually Wrapped (Product # 3524) Corning Incorporated, USA) in each well to make a fibrin gel. The aortic ring was placed in the central part of each well and overlaid with another fibrin gel (fibrinogen solution 0.4 mL). Furthermore, the gel was covered with MCDB131 culture medium (1.5 mL) and cultured under conditions of 37 ° C., 3% CO ₂ /97% air. Shark meat extract alone or shark meat extract + lecithin was added to the culture as a supplement. Three samples of shark meat extract alone or each of shark meat extract + lecithin were prepared and analyzed. Only the culture broth was analyzed as a control.

  It should be possible to confirm that microvessels have grown from around the ring (both outside and inside the ring) after approximately 5 days. From day 5 to day 14, images of each well were recorded at regular intervals. A digital camera (Pixera PVC-100C digital camera) attached to an inverted microscope (OLYMPUS CK-12 microscope) was used for photography. The growth range of microvessels around the ring was determined for each image using NIH Image 1.59 software (http://rsb.info.nih.gov/nih-image/about.html.). At each time point, the average of the growth rate (specimen A / control A × 100 = growth rate, A = new blood vessel area extending from the outer ring of the ring + new blood vessel area extending to the inner ring of the ring) ÷ area of the ring itself) Determined, microvascular growth rate was determined for shark meat extract alone and shark meat extract + lecithin, and angiogenesis inhibition rate was calculated.

  Table 1 shows the anti-angiogenic action of a composition containing shark meat extract and lecithin (labeled as shark meat extract + lecithin). When lecithin is added, the anti-angiogenic effect of the extract is more than doubled. The 52.3% inhibition rate provided by shark meat extract + lecithin indicates a synergistic anti-angiogenic effect brought about by mixing lecithin with shark meat extract.

Preparation of mussel meat extract + lecithin green mussel (Perna canaliculus) meat extract As in the case of the shark meat extract of Example 1, freeze-dried powdered green mussel meat was extracted with ethanol, filtered and solvent removed. Prepared.
The anti-angiogenic activity of green mussel meat extract and green mussel meat extract + lecithin was evaluated in the same manner as in Example 1.

  Table 2 shows the anti-angiogenic activity of green mussel extract and green mussel + lecithin. Green mussel extract alone showed a slightly lower anti-angiogenic effect than shark meat extract alone. When lecithin was added to the green mussel meat extract, its anti-angiogenic activity increased significantly (about 2-fold).

  The effect of lecithin to enhance the anti-angiogenic activity of the extract with anti-angiogenic activity was further supported by the green mussel extract data. Green mussel extract has a relatively weak anti-angiogenic effect (in fact, it is known that green mussel extract has an anti-inflammatory effect (WO / 2006/052150)). However, when lecithin was added at a ratio of 4: 1, the anti-angiogenic effect was unexpectedly increased by about 2 times.

  The fact that lecithin enhances both anti-angiogenic effects of shark meat extract and mussel meat extract also demonstrates synergistic (enhanced) effects in various other natural product extracts with anti-angiogenic activity Suggests to do.

  Although the present invention has been described with reference to examples, various applications or improvements are possible without departing from the scope of the invention. Furthermore, substances known to have similar characteristics are to be treated in the same manner as detailed in this specification.

  The invented anti-angiogenic composition is useful for the treatment and prevention of a wide variety of diseases. These diseases include diseases involving angiogenesis such as arthritis, retinopathy, macular degeneration, psoriasis, and cancer.

Claims (8)

From the group consisting of arthritis, retinopathy, macular degeneration and cancer where disease or disorder is beneficial to inhibit angiogenesis , including mixing lecithin with shark and / or mussel-derived lipids A method for producing a composition for treating or preventing a selected disease or disorder . The method for producing a composition according to claim 1, wherein the mussel is New Zealand green mussel. Furthermore, the manufacturing method of the composition of Claim 1 or 2 including adding edible oil. The method for producing a composition according to claim 3, wherein the edible oil is olive oil. Furthermore, the manufacturing method of the composition of any one of Claims 1-4 including adding vitamin E. The method for producing a composition according to any one of claims 1 to 5, wherein the weight ratio of shark meat and / or mussel-derived lipid and lecithin is in the range of 1: 1 to 10: 1. The manufacturing method of the composition of Claim 6 whose weight ratio is 4: 1-5: 1. It is a pharmaceutical method for producing a composition according to any one of claims 1-7.