JP7260952B2 - shoulder pain reliever - Google Patents

Description

TECHNICAL FIELD The present invention relates to a shoulder pain ameliorating agent for alleviating shoulder pain.

Anatomically, the shoulder joint refers to the glenohumeral joint, which consists of the head of the humerus and the glenoid socket of the scapula. Also includes joints and scapulothoracic joints. Although the shoulder joint has excellent mobility, the contact area of the joint surface is small and unstable. Therefore, when degenerative changes occur in the surrounding tissues with aging, shoulder pain is said to occur especially after middle age, especially in the 50's.

Conventionally, methods such as rest, drug therapy, conservative therapy such as hyperthermia, and surgical therapy have been applied as methods for ameliorating or treating shoulder pain. Non-steroidal anti-inflammatory drugs (NSAIDs) are mainly used as drugs for improving or treating shoulder pain. In addition, hyaluronic acid injection, nerve block injection therapy, supplements containing glucosamine, chondroitin, etc., external medicines such as poultices containing anti-inflammatory analgesic ingredients, lotions, creams, ointments, etc. are also used (for example, Patent Document 1). However, the effect is still insufficient, and the guidance of doctors and other medical personnel is required to implement conservative therapy or surgical therapy. There is a desire for a method to improve the

On the other hand, Milk-fat Globule Membrane (MFGM) is a membrane component that covers the milk fat globules secreted from the mammary glands, and is abundant in milk complex lipid-rich fractions such as buttermilk and butter serum. It is known to be included (Non-Patent Document 1). It has been reported that milk fat globule membranes not only have the function of dispersing fat in milk, but also have physiological functions such as improving motor function and improving muscle strength in mice (Patent Document 2).
However, there is no report on the effect of milk fat globule membrane on shoulder pain.

JP 2014-114232 A JP 2010-59155 A

Susumu Miura, FOOD STYLE21, 2009

TECHNICAL FIELD The present invention relates to providing pharmaceuticals, quasi-drugs or foods useful for alleviating shoulder pain, or materials or formulations that can be blended therein.

In view of the above problems, the present inventors conducted intensive studies and found that milk fat globule membranes are useful for alleviating shoulder pain.

That is, the present invention provides a shoulder pain ameliorating agent containing milk fat globule membranes as an active ingredient.
In addition, the present invention provides a food for alleviating shoulder pain containing milk fat globule membranes as an active ingredient.

ADVANTAGE OF THE INVENTION According to this invention, the pain of a shoulder can be reduced and the pain of a shoulder can be improved.

The graph which shows the result of VAS evaluation.

The milk fat globule coating used in the present invention is defined as the mixture of membranes that coat the milk fat globules and the ingredients that make up the membrane. Milk fat globule membranes have a wealth of food experience and are highly safe.
About half of the dry weight of the milk fat globule membrane is generally composed of lipids, and it is known that the lipids include triglycerides, phospholipids, and glycosphingolipids (Susumu Miura, FOOD STYLE 21, 2009 and Keenan TW, Applied Science Publishers, 1983, pp89-pp130). Phospholipids are known to include sphingophospholipids such as sphingomyelin (SM), glycerophospholipids such as phosphatidylcholine (PC), phosphatidylethanolamine (PE) and phosphatidylserine (PS).
In addition, it is known that a glycoprotein called milk mucin is included as a component other than lipids (Mather, Biochim Biophys Acta, 1978).

From the viewpoint of physiological effects, the milk fat globule membrane used in the present invention preferably has a lipid content of 10% by mass or more, further 20% by mass or more, further preferably 30% by mass or more. Also, from the viewpoint of flavor and handling, it is preferably 100% by mass or less, further 90% by mass or less, and further 60% by mass or less.

From the viewpoint of physiological effects, the milk fat globule membrane preferably has a phospholipid content of 5% by mass or more, further 8% by mass or more, further 10% by mass or more, further 15% by mass or more. It is preferably 100% by mass or less, more preferably 85% by mass or less, more preferably 70% by mass or less, and even more preferably 60% by mass or less from the viewpoint of flavor and handling.

From the viewpoint of physiological effects, the milk fat globule membrane preferably has a sphingomyelin (SM) content of 1% by mass or more, further 2% by mass or more, and further 3% by mass or more. In terms of flavor and handling, it is preferably 50% by mass or less, further 30% by mass or less, further 25% by mass or less, and furthermore 20% by mass or less.
From the same point, the sphingomyelin content in the total phospholipids of the milk fat globule membrane is preferably 3 mass% or more, further 5 mass% or more, further 10 mass% or more, further 15 mass% or more, and , 50 mass % or less, further 40 mass % or less, further 35 mass % or less, further 30 mass % or less.
In the present specification, the content of lipids and phospholipids in the milk fat globule membranes, and the content of sphingomyelin in the total phospholipids of the milk fat globule membranes are the ratio by mass to the dry matter of the milk fat globule membranes. do.

Milk fat globule membranes can be obtained from raw milk by known methods such as centrifugation and organic solvent extraction. For example, a method for preparing a milk fat globule film described in JP-A-3-47192 can be used. Also, the methods described in Japanese Patent No. 3103218 and Japanese Patent Application Laid-Open No. 2007-89535 can be used.
Further, it is also possible to use one whose purity has been increased by purification by techniques such as dialysis, ammonium sulfate fractionation, gel filtration, isoelectric precipitation, ion exchange chromatography, and solvent fractionation.
The form of the milk fat globule film is not particularly limited, and may be liquid, semi-solid (paste etc.), solid (powder, solid, granules etc.) at room temperature (15 to 25° C.). They may be used alone or in combination of two or more, but are preferably solid (powder).

Raw milk for the milk fat globule membrane includes cow's milk and goat's milk. Among them, cow's milk is preferable because it is widely used as a food and is inexpensive. In addition, raw milk includes milk such as raw milk, whole milk powder and processed milk, as well as dairy products. Dairy products include buttermilk, butter oil, butter serum, whey protein concentrate (WPC) and the like. be done.
Buttermilk is obtained when butter grains are produced from cream obtained by centrifuging milk or the like, and since the buttermilk contains a large amount of milk fat globule membranes, it is You can use it as it is. Similarly, butter serum produced in the production of butter oil also contains a large amount of milk fat globule membranes, so butter serum may be used as it is as milk fat globule membranes.

A commercial product can also be used for the milk fat globule membrane. Examples of such commercially available products include "BSCP" from Megret Japan Co., Ltd., "Milk Ceramide MC-5" from Snow Brand Milk Products Co., Ltd., and "Phospholipid Concentrate Series (500, 700)" from New Zealand Milk Products Co., Ltd.

The shoulder pain ameliorating agent of the present invention may further contain glucosamine or a salt thereof from the viewpoint of improving the shoulder pain ameliorating effect of the milk fat globule membrane.
Glucosamine is _a compound represented by _the molecular formula _C6H13NO5 . Glucosamine may be a D-isomer, an L-isomer, or a DL-isomer in which both isomers are mixed, but the D-isomer is preferred. Moreover, it may be either α-type or β-type.
Salts of glucosamine include, for example, inorganic salts such as hydrochloride, sulfate, and phosphate; acetate, propionate, tartrate, fumarate, maleate, malate, citrate, methane Organic acid salts such as sulfonates, p-toluenesulfonates and trifluoroacetates are included, and hydrochlorides are preferred.
These glucosamines or salts thereof can be used alone or in combination of two or more.
Glucosamine or a salt thereof may be produced by known methods such as enzymatic treatment of chitin obtained from crustaceans such as crabs and shrimps, hydrolysis, microbial fermentation, and chemical synthesis, or commercially available products may be used. .

In the present invention, when milk fat globule membranes and glucosamine or a salt thereof are used in combination, the ratio is determined by the mass ratio of the content of milk fat globule membranes (in terms of dry matter) to the amount of glucosamine equivalent [milk fat globule membrane/glucosamine], preferably 0.15 or more, more preferably 0.3 or more, still more preferably 0.5 or more, and preferably 10 or less, more preferably 5 or less, more preferably 1 It is below.

As shown in the examples below, milk fat globule membranes have the effect of significantly alleviating shoulder pain.
Therefore, the milk fat globule membrane can be a shoulder pain ameliorating agent useful for ameliorating shoulder pain, and can be used to produce a shoulder pain ameliorating agent. That is, milk fat globule membranes can be applied to people who are concerned about shoulder pain and used to improve shoulder pain.
Here, "shoulder pain" is shoulder pain and includes shoulder joint pain. The shoulder joint includes the glenohumeral joint composed of the head of the humerus and the glenoid socket of the scapula, the acromioclavicular joint, the sternoclavicular joint, the second shoulder joint, and the scapulothoracic joint.
"Amelioration" refers to amelioration of symptoms or conditions, prevention, inhibition or delay of worsening of symptoms or conditions, or reversal, prevention, inhibition or delay of progression of symptoms or conditions.
"Use" can be administration or ingestion to humans, and can be therapeutic or non-therapeutic use. "Non-therapeutic" means a concept that does not include medical practice, i.e., a concept that does not include methods of surgery, treatment or diagnosis of humans, more specifically, surgical procedures performed on humans by a physician or a person under the direction of a physician. , is a concept that does not include methods of performing therapy or diagnosis.

The shoulder pain ameliorating agent of the present invention is a drug, quasi-drug, or food that exerts an effect of alleviating shoulder pain when ingested or administered to animals including humans. , quasi-drugs, or materials or formulations that are used by blending in foods.

Such foods include foods with the concept of alleviating shoulder pain, and permitted to be labeled as such (foods for specified health uses, foods with function claims) as necessary. These foods can be distinguished from ordinary foods because they are foods with functional claims.

Examples of dosage forms of the pharmaceuticals (including quasi-drugs, hereinafter the same) include oral administration using tablets, capsules, granules, powders, troches, syrups, and the like.
Formulations of such various dosage forms can be prepared using the milk fat globule coatings of the present invention or other pharmaceutically acceptable carriers such as excipients, binders, extenders, disintegrants, surfactants, lubricants. Lubricants, dispersants, buffers, preservatives, flavoring agents, fragrances, coating agents, carriers, diluents, etc., and medicinal ingredients other than the milk fat globule coating can be appropriately combined for preparation.
Among them, preferred dosage forms are solid preparations for oral administration, and tablets are preferred.

The content of the milk fat globule membrane in the drug (in terms of dry matter) is generally 0.01% by mass or more, preferably 0.1% by mass or more, more preferably 0.2% by mass or more, and still more preferably. is 1% by mass or more, and is preferably 90% by mass or less, more preferably 80% by mass or less, still more preferably 70% by mass or less, and still more preferably 60% by mass or less.

Examples of the form of the food include beverages such as soft drinks, tea drinks, coffee drinks, fruit juice drinks, carbonated drinks, jellies, wafers, biscuits, breads, noodles, sausages, and various food compositions such as nutritious foods. Furthermore, nutritional supplement compositions in the same form as the oral administration formulations described above (solid formulations such as tablets, capsules, and lozenges) are also included. Among them, solid preparations are preferred, and tablets are more preferred.

Foods in various forms may contain milk fat globule membranes, or other food ingredients, solvents, softeners, oils, emulsifiers, preservatives, acidulants, sweeteners, bittering agents, flavors, stabilizers, colorants, oxidants. It can be prepared by appropriately combining an inhibitor, a moisturizing agent, a thickener, an active ingredient other than the milk fat globule film, and the like.

The content of the milk fat globule membrane in the food (in terms of dry matter) varies depending on the form of use. is 0.1% by mass or more, preferably 3% by mass or less, more preferably 2% by mass or less, and even more preferably 1% by mass or less.

In the form of solid foods such as tablets and processed foods, the content of milk fat globule membranes (on a dry matter basis) is preferably 0.05% by mass or more, more preferably 0.1% by mass or more, and still more preferably 0.1% by mass or more. It is 2% by mass or more, preferably 90% by mass or less, more preferably 80% by mass or less, even more preferably 70% by mass or less, and even more preferably 60% by mass or less.

The dosage or intake of the shoulder pain ameliorating agent of the present invention may vary according to the body weight, sex, age, condition or other factors of the subject of administration or intake. The dose, route, interval of administration, and the amount and interval of intake can be appropriately determined by those skilled in the art, but usually, per day per adult (60 kg), as milk fat globule film (converted to dry matter) , preferably 0.1 g or more, more preferably 0.3 g or more, still more preferably 1 g or more, and preferably 30 g or less, more preferably 20 g or less, still more preferably 10 g or less.
In general, per adult (60 kg) per day, sphingomyelin is preferably 10 mg or more, more preferably 20 mg or more, still more preferably 40 mg or more, and preferably 1500 mg or less, more preferably It is 1000 mg or less, more preferably 500 mg or less, and still more preferably 250 mg or less.

In the present invention, it is preferable to administer or take such an amount once or several times a day.

The formulations can be administered or taken according to any schedule.
The period of administration or intake is not particularly limited, but it is preferable to administer or intake repeatedly and continuously, more preferably to administer or intake continuously for 5 days or more, and to administer or intake continuously for 15 days or more. More preferred.

The subject of administration or intake is not particularly limited as long as it is a person who has shoulder pain and needs or desires improvement of shoulder pain, but administration or intake to a person who is aware of shoulder pain is effective. .

[Preparation of tablets]
Tablets (Example 1: 353 mg/tablet, Comparative Example 1: 450 mg/tablet) having the composition shown in Table 1 below were prepared according to the Japanese Pharmacopoeia (General Rules for Formulations, "Tablets").

A milk fat globule membrane (MFGM) prepared from cow's milk was used.
The water content of MFGM was 3.6 mass %. The composition of MFGM was carbohydrate: 11.3% by mass, lipid: 25.1% by mass, and protein: 53.6% by mass in terms of dry matter. In MFGM, the phospholipid content was 16.6% by mass and the sphingomyelin content was 3.6% by mass in terms of dry matter.

Analysis of the above MFGM was performed as follows.
(1) Analysis of protein The amount of protein was determined using the Kjeldahl method with a nitrogen/protein conversion factor of 6.38.

(2) Analysis of lipids The amount of lipids was determined by an acidolysis method. After weighing 1 g of a sample and adding hydrochloric acid to decompose it, diethyl ether and petroleum ether were added and mixed with stirring. The ether mixture layer was taken out and washed with water. After distilling off the solvent and drying, the weight was measured to determine the amount of lipid.

(3) Carbohydrate analysis The carbohydrate content was obtained by removing the protein content, lipid content, ash content, and water content in the sample from the mass of the sample. The ash content was determined by a direct incineration method (a sample was incinerated at 550°C and weighed), and the moisture content was determined by a normal pressure drying method (dried at 105°C for 4 hours and weighed).

(4) Analysis of phospholipids Weigh 1 g of the sample, homogenize in 150 mL, 100 mL, and 20 mL of a 2:1 (V/V) mixture of chloroform and methanol, and then 0.88 wt% (W/V) potassium chloride aqueous solution. 93 mL was added and left overnight at room temperature. After dehydration filtration and solvent distillation, chloroform was added to bring the total volume to 50 mL. A 2 mL portion thereof was taken, and after distilling off the solvent, it was incinerated by heat treatment at 550° C. for 16 hours. After dissolving the ash in 5 mL of a 6 M hydrochloric acid aqueous solution, distilled water was added to bring the total volume to 50 mL. A 3 mL portion was taken, 5 mL of molybdenum blue coloring reagent, 1 mL of 5% by mass (W/V) ascorbic acid aqueous solution, and distilled water were added to make the total volume 50 mL, and the absorbance at 710 nm was measured. The amount of phosphorus was obtained from a calibration curve using potassium dihydrogen phosphate, and the amount of phosphorus was multiplied by 25.4 to obtain the amount of phospholipid.

(5) Analysis of sphingomyelin A 1 g sample was weighed and homogenized in 150 mL, 100 mL, and 20 mL of a 2:1 (V/V) mixture of chloroform and methanol, followed by a 0.88 wt% (W/V) potassium chloride aqueous solution. 93 mL was added and left overnight at room temperature. After dehydration filtration and solvent distillation, chloroform was added to bring the total volume to 50 mL. 10 mL of this was taken out and added to a silica cartridge column. After washing the column with 20 mL of chloroform, the phospholipid was eluted with 30 mL of methanol, and after the solvent was distilled off, it was dissolved in 1.88 mL of chloroform. 20 µL was loaded on a silica gel thin layer plate, and tetrahydrofuran:acetone:methanol:water = 50:20:40:8 (V/V) was used as the one-dimensional developing solvent, and chloroform:acetone:methanol:acetic acid:water was used as the two-dimensional developing solvent. =50:20:10:15:5 (V/V) was used for two-dimensional development. A Ditmer reagent was sprayed on the developed thin layer plate, the sphingomyelin spot was scraped off, 2 mL of a perchloric acid solution containing 3% by mass (V/V) nitric acid was added, and heat treatment was performed at 170° C. for 3 hours. After adding 5 mL of distilled water, 5 mL of molybdenum blue coloring reagent, 1 mL of 5% by mass (W/V) ascorbic acid aqueous solution and distilled water were added to bring the total volume to 50 mL, and the absorbance at 710 nm was measured. The amount of phosphorus was determined from a calibration curve using potassium dihydrogen phosphate, and the amount of sphingomyelin was obtained by multiplying the amount of phosphorus by 25.4.

[Comparative verification study by double-blind randomized parallel design]
(1) Subjects and test method Healthy men and women in their 50s to 70s were divided into two groups, an MFGM group and a placebo group (22 people in each group). 10 tablets), and the placebo group took the tablets of Comparative Example 1 (total of 7 tablets) containing no MFGM every day for 6 weeks at any time.

(2) Evaluation of shoulder pain amelioration effect Evaluation of the shoulder pain amelioration effect was carried out using a visual analogue scale (VAS) that asks about the degree of shoulder pain. Specifically, before the start of the test (week 0) and 6 weeks after the start of the test, the left end 0 mm of the 100 mm straight line was "no pain" (numerical value 0), and the right end 100 mm was "the most severe pain ever experienced". As a feeling of (numerical value 100), the degree of pain in the shoulder for several days was marked on a 100 mm straight line with reference to the sensations indicated on the left and right ends of the straight line.

(3) Statistics and Results 17 subjects in the MFGM group and 20 subjects in the placebo group who answered that they had shoulder pain before the start of the study (week 0) were included in the final analysis.
Regarding the numerical values (VAS values) of 37 subjects for the final analysis after 6 weeks, the differences (Δ values) from the initial values for each group were calculated and shown in FIG.
The obtained numerical values are shown as mean±standard error. For statistics, student's t-test was used with a significance level of 5%.
As shown in FIG. 1, there was no significant difference in the degree of shoulder pain after the end of the test compared to before the start of the test in the MFGM group compared to the placebo group, but there was a tendency toward improvement (p=0.07). From this, it was confirmed that MFGM significantly improved shoulder pain.

Claims (12)

An oral shoulder pain ameliorating agent containing milk fat globule membranes as an active ingredient (excluding use as an ameliorating agent for shoulder pain caused by osteoarthritis). The oral shoulder pain ameliorating agent according to claim 1, wherein the milk fat globule membrane contains 5 to 100% by mass of phospholipid. The oral shoulder pain ameliorating agent according to claim 1, wherein the milk fat globule membrane contains 1 to 50% by mass of sphingomyelin. The oral shoulder pain ameliorating agent according to any one of claims 1 to 3, which is in the form of a solid preparation. 5. The oral shoulder pain ameliorating agent according to claim 4, wherein the solid preparation is a tablet. The oral shoulder pain ameliorating agent according to any one of claims 1 to 5, wherein 10 to 1500 mg of sphingomyelin is orally administered or orally ingested per adult per day. A food for ameliorating shoulder pain containing milk fat globule membranes as an active ingredient (excluding use as a food for ameliorating shoulder pain due to bone and joint diseases). The shoulder pain ameliorating food according to claim 7, wherein the milk fat globule membrane contains 5 to 100% by mass of phospholipid. The shoulder pain ameliorating food according to claim 7, wherein the milk fat globule membrane contains 1 to 50% by mass of sphingomyelin. The shoulder pain ameliorating food according to any one of claims 7 to 9, wherein the dosage form is a solid preparation. The shoulder pain ameliorating food according to claim 10, wherein the solid preparation is a tablet. The food for ameliorating shoulder pain according to any one of claims 7 to 11, wherein 10 to 1500 mg of sphingomyelin is orally administered or ingested per adult per day.

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