JPH02200639A - Lipid coated bacterium preparation - Google Patents

Abstract

PURPOSE:To obtain a bacterium preparation capable of being administered orally, having excellent acid resistance by sticking lipid powder to the whole circumferential surface of bacterium powder pulverized by lyophilization. CONSTITUTION:Lipid powder having >=40 deg.C melting point is brought into contact with or collided against bacterium powder (preferably one having 0.5.mum-1mm particle diameter) itself or pulverized by lyophilization or mixed bacterium powder containing edible powder (e.g. lactic acid, milk powder or starch) and the lipid powder is stuck to the whole circumferential surface of the bacterium preparation. Bacteria in the intestine such as Lactobacillus bifidus, lactic acid bacillus, yeast fungus, bacteria belonging to the genus Streptococcus are used as the bacterium powder. Natural fats and oils, wax, fatty acid, etc., are used as the lipid powder, the ratio of particle diameter of the bacterium powder and the lipid powder is (1:1)-(1:0.0001) and the blending ratio is 0.5-50 (adjusted in relation to the ratio of particle diameter).

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention relates to a bacterial preparation prepared by an improved formulation and used as an orally administrable medicine.

[Prior Art] It is known that intestinal bacteria have a beneficial effect on human digestive activity in the human body, especially in the digestive organs starting from the small intestine.
Hereinafter, such bacteria will be referred to as Ishikawa bacteria). It is also widely known that pharmacological effects can be expected by oral administration of Ishikawa bacteria.

However, in general, it is difficult for these useful bacteria to survive in an acidic atmosphere, and even if useful bacteria are administered orally to humans, most of them will die due to the action of stomach acid and the like.

An improved method has been proposed to avoid this problem (Japanese Patent Application Laid-open No. 263128/1982). This is a method to make useful bacteria into a three-layer seamless capsule. However, these conventional manufacturing methods are extremely complicated, difficult to manufacture, and expensive in terms of cost, and are far from practical.

[Problems to be Solved by the Invention] The present invention is intended to solve the above-mentioned problems in the prior art, and aims to improve useful bacteria that are extremely unstable in an acidic atmosphere using a practical manufacturing method and manufacturing cost. The object of the present invention is to provide a useful bacterial preparation that can be industrially administered orally, and to enable its use as a medicine.

Therefore, the present invention aims to provide an orally administrable useful bacterial preparation that can be practically used as a medicine.

[Means for Solving the Problem] As a result of intensive research to obtain an industrially orally administrable useful bacterial preparation for the above-mentioned problem, the present inventors discovered a coating material that can substantially coat useful bacteria, The invention has been completed. That is, the present invention allows lipids to be attached to the entire peripheral surface of bacterial powder particles by contact or collision with lipid powder having a melting point of 40° C. or higher, and to produce useful bacteria that can be industrially orally administered using a method and manufacturing cost. The present invention provides a useful bacterial preparation and enables its use as a medicine.

Examples of useful bacteria that can be used in the present invention include Bifidobacterium bifidus.
bifidus), Bifidobacterium longum (B.
s), Bifidobacterium breve (f3.
breve), bifidobacteria such as Bifidobacterium infantis (B, 1nfantis), and Lactobacillus acidophilus (Lactobacillus acidophilus).
cillus acidophilus), Lactobacillus lactis (L, Iactis), Lactobacillus casei (L, casei), Lactobacillus bulgaricus (L, bulgaricus)
), Streptococcus lactis (5
Streptococcus Iactis), and Streptococcus faecalis (S.

Examples include lactic acid bacteria such as L. aecalis.

These bacteria are collected using conventional methods such as centrifugation from the M fermentation culture solution, quickly frozen, and then dried in a high vacuum atmosphere to form a powder through so-called freeze-drying. used. At this time, depending on the state of the bacteria, edible powder such as L-lactic acid, skim milk powder, or starch may be mixed in before or after freezing.

The particle size of the above bacterial powder is usually 0.5 Fml to 1.0 m.
m is preferred. Moreover, the shape can be spherical or irregular. The lipid powder of the present invention used as a coating material includes natural oils and fats with a melting point of 40°C or higher, hydrogenated oils, waxes, fatty acid monoglycerides,
Fatty acid diglycerides, fatty acids, and other edible fats and oils can be used, and one type or a mixture of two or more of these can also be used.

The particle size ratio of bacterial powder and coating agent is from 1:1 to 0.0.
001 is preferably used. Also, the mixing ratio is 0 in terms of weight ratio.
．． Although it is possible to use it in the range of 5 to 50, it is desirable to adjust it in relation to the particle size ratio. That is, appropriate conditions are selected and determined so that the coating agent evenly adheres to and coats the entire surface of the bacterial powder particles.

[Examples] Hereinafter, the present invention will be described in detail based on Examples, but the scope of the present invention is not limited thereby.

Example 1 Lyophilized mixed powder of Bifidobacterium longum (hereinafter referred to as B, Iongum) and starch (B, Iongum 1.3 x 109 pieces/g)
'tB powder) 42 g (average particle size 1101311) and 21 g rapeseed hydrogenated oil (average particle size 8.6F, melting point 64.1'C: manufactured by Nippon Oil & Fats Co., Ltd.) were mixed together with 20 brass poles in a centrifugal rotating type. Place in a mixer (Takano Mill MMIO: manufactured by Kaida Seiko Co., Ltd.) and mix at a rotational speed of 300 r, p, +*, 4
After mixing for a period of time, 63 g of coated formulation was obtained. Electron the surface of the resulting coated preparation! When observed with an rI microscope, it was found that an extremely good coating was formed.

Furthermore, when the number of viable bacteria of B, 1 ocus of coated preparation was measured, it was found that B, Iongum O, 9X 109 cells/
It was confirmed that the loss rate associated with the coating process was almost negligible with the G formulation, and that the two freeze-dried live bacteria were stably treated in the coating process.

Example 2 In order to create an acidic environment, 0.1% by weight of untreated raw material was added to a phosphate buffer solution of pH 4.0 and pH 5.0 maintained at 37°C, which was prepared as a model as an artificial gastric acid solution. B.

Example 1 except that hydrogenated oil was used as the Iomgu powder and coating material, and the mixing ratio of bacterial powder and coating material was 1:1.
B, logum (coating treatment B, Iongum), which was made into a coating preparation according to the above, was added, and while stirring, the number of viable bacteria was measured at predetermined time intervals by a known method. Tables 1 and 2 show the results expressed as survival rate (%) with the number of bacteria as 100.

From the results in Table 1, it can be seen that while the untreated B. lomgum died in a short period of time, the coated B. lomgum of the present invention showed a fairly stable survival state. was confirmed. It was also confirmed that Table 2 was not concluded.

Example 3: 0.1% by weight of untreated Streptococcus faecalis (hereinafter abbreviated as S. faecalis) in a phosphate buffer with pH 6.9 and po 5.0 kept at 37°C.
The number of viable bacteria was measured by a known method in accordance with Example 1, except that hydrogenated oil was used for the powder and coating material, and the mixing ratio of bacterial powder and coating material was 6=4. Tables 3 and 4 show the results expressed as survival rate (%), where the number of viable bacteria per minute was ioo.

From the results in Table 3, it was confirmed that under neutral conditions (pH 6, 9), untreated S and faecalis tended to decrease slightly, but coated S and faecalis were not affected at all. Also, from the results in Table 4, under acidic conditions (pH 5, 0), untreated S, faecal
is shows a tendency to decrease significantly, but after coating treatment S,
faecalig was found to be relatively unaffected.

Margin below Example 4: 0.1% by weight of untreated Lactobacillus acid 7 in phosphorous buffer solutions of pH 6.9 and pH 5.0 maintained at 37°C.
A coating preparation was prepared according to Example 1, except that L. acidophilus (hereinafter abbreviated as L) and hydrogenated oil were used as the coating agent, and the mixing ratio of bacterial powder and coating agent was 4:6. Or, Acidophilus (coated treated, Acidophilus) was added, and the number of viable bacteria was measured at each predetermined time while stirring, using a known method. ) The results are shown in Tables 5 and 6.

From the results in Table 5, it was confirmed that under neutral conditions (pH 6, 9), untreated acidophilus tended to decrease slightly, but coated acidophilus was hardly affected. Also, from the results in Table 6, even under acidic conditions (pH 5, 0), untreated acidophilus tends to decrease slightly, but coated acidophilus tends to decrease.
It was confirmed that it was not affected at all.

[Test Example] Coated bacterial preparation B prepared by the same method as Example 1,
Iongum, as well as untreated B, Iongu+w, were stored at room temperature in closed containers to determine their stability over time. 1, 3 with the number of viable bacteria at the time of production being 100
．． 6. and survival rate (%) at each time point after 9 months
The results expressed in Table 7 are shown in Table 7.

From the results in Table 7, it was confirmed that the coated bacterial preparation of the present invention had superior storage stability over time compared to untreated bacteria at any time point.

Margins below] 5 [Effects of the Invention] As described above, the coated bacterial preparation of the present invention is extremely easy to manufacture compared to conventional bacterial preparations, and therefore enables a significant reduction in manufacturing time and cost.

In addition, the drawback of conventional bacterial preparations is that they cannot be placed under acidic conditions6.
It has improved stability and can be effectively used as a medicine that can be administered orally. Furthermore, it is possible to block out external air and moisture, prevent contact with other components, and have excellent storage stability, which has useful effects that improve commercial value.

Claims (1)

[Claims] 1) At least one kind of lipid powder having a melting point of 40°C or more is brought into contact with the bacterial powder itself or the mixed bacterial powder containing edible powder, which has been powdered by freeze-drying. 2) The lipid-coated bacterial preparation according to claim 1, characterized in that the bacterial powder is an enteric bacterium. Bacterial preparation 3) The lipid-coated bacterial preparation according to claim 2, wherein the intestinal bacteria are selected from the group of bacteria belonging to the genus Bifidobacteria, Lactobacillus, Yeast, and Streptococcus 4) The bacterial powder is 5) The lipid-coated bacterial preparation according to claim 1, wherein the edible powder is one or more powders selected from the group of lactic acid, milk powder, and starch. 6) The lipid-coated bacterial preparation according to claim 1, wherein the lipid powder is a fatty acid or an edible fat such as hydrogenated oil. ) The lipid-coated bacterial preparation according to claim 1, 2, 3, 4, 5, or 6, characterized in that it is used as an orally administrable pharmaceutical.