JPS6183128A - Useful bacteria drug for internal use and its production - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

DETAILED DESCRIPTION OF THE INVENTION Industrial Field of Application The product according to the present invention is produced by chemical formula 11: useful bacteria as general and medical drugs or R products, and is a scale.

Conventional Techniques The conventional technology for delivering living useful 1η into the intestines was to use the useful casing and its nutrients as a mixture, or to make the useful bacteria into a spore state, as described below. As such, these techniques are imperfect.

The problem that the invention aims to solve: Immediately after a human being is born as a newborn, 7I bacteria proliferate in the boar membranes of the digestive tract.
Published by Soubunsha), Intestinal cylinder Haranos 1J) Where can you get it;)
J) The balance between the two is determined by ``S (in the case of humans, the host's physiology, the interaction of intestinal bacteria, food, drugs, climate, etc.) (above -) changes.Assuming host physiology, 1, +)l in the digestive tract,
Examples include the exertion of the digestive system, endocrine secretions such as enzymes, bile, α-α, and antibodies. The pond can easily fluctuate due to physical or mental stress. In particular, antibiotics disrupt the intestinal lining. Products of non-useful or pathogenic bacteria include ammonia, hydrogen sulfide amine, phenol, carcinogenic 1 biological trade, toxins in the pond, diarrhea/constipation, dystonia, and liver F.
It causes damage, decreased resistance, cancer, high blood pressure, etc., and as a result, it leads to aging. On the other hand, useful bacteria must maintain β2 health by synthesizing vitamins and proteins, assisting in digestion and absorption, preventing proliferation before outpatient treatment, promoting immunity, and stimulating the immune system, or there may be disturbances as mentioned above. It is necessary to send the bacteria into the intestines in a well-balanced manner at an appropriate bacterial flora ratio. However, when administered orally, gastric juices mix with the food, the pH drops, and the acid-sensitive bacteria are killed.When the number of bacteria decreases, the gate opens and the food is sent to the duodenum. Useful bacteria: Used in many pharmaceuticals and foods, both for medical and general use, and has anti-intestinal, anti-loose, anti-fecal properties (and anti-11W
As can be seen in the following experimental example, the rate of useful bacteria in the preparation reaching the intestines is low, and their activity may be weakened. .

Therefore, in the intestines, there is a high fii rate in which useful substances already produced from the bacterial bodies are mainly used.

As a means to solve the problem, the useful main seedlings were compressed into tablets and coated to eliminate oxygen and to protect the useful bacteria from t-ma and alpha and improve growth efficiency (continuous research). As a result, we have completed the present invention.The activity of anaerobic bacteria such as Hyphytobacterium is reduced by air if it is simply compressed or powdered, or becomes airtight by coating.1 The present invention will be described with reference to experiments and examples below. However, the scope of the present invention will be limited by the examples. In addition to this, enzymes that are sensitive to acids and oxygen can also be added.

Nari'1-te? In the case of kneading, it is possible to greatly increase the survival rate of useful bacteria if the coated bun is cooled.

Experiment l a+;f 15 mg of seedling bundles (a mixture of 7 N. tophilus bacteria and P. felicus) were added to artificial gastric juice (PH1, 2) and physiological saline (PH 6, 8), 10 to 111, respectively, and placed in a Heng-I-Chang oven at 37°C. The artificial bone IC2 was shaken for 1 hour in a bath and the [)H of the artificial bone IC2 was adjusted to be the same as that of fresh L1 saline. a
5'2 Bacterial A "Susada" is a BCP addition plate count force -
A sample of 1 g of water was collected at 37 C for 72 hours to determine ρ7.

The result of hr Moe is that the number of viable bacteria per g is 2.000.000 for n,q (physiological saline treated product) and 2 for artificial gastric juice treated product.
000 or less.

Experiment 2 Add 100 ml of physiological saline to each of the artificial stomachs containing alpha 5+B and incubate them for 1 hour in constant temperature at 37'C. I)
H was adjusted to be the same as saline J3 water. A: Measurement of acid bacteria: B
1 history of CP addition plate count Akar, 37
Calculated after culturing at 'C for 72 hours.

The result of the ring drawing is that the number of general viable bacteria per g is 3.800.000 for the control (saline treated product) and 35 for the artificial fog Iα treated product.
It was below 00.

Experiment 3 1 g of diluted Bifidobacterium powder was added to 100 g of artificial gastric fluid and physiological saline, and after shaking for 1 hour in a constant temperature bath of 1,37 (','), the pH of the artificial gastric juice was was adjusted to be the same as physiological saline.For the measurement of lactic acid bacteria, BCP-added plate count agar was cultured for 72 hours in 1 Fumikawa L 37C and S1 was taken out.Results of ring drawing: Yo: General raw material per I. The number of bacteria is 1.000.00 for the physiological saline treated product.
0. OOQ was 550 for the artificial gastric juice treated product.

Experiment 4 Bifidobacterium, plant fibers, calcium hydrogen phosphate, lactose, crystalline cellulose, potato starch, stearate, /, - were mixed, and the initial number of Bifidobacterium was 149.0 liters per g. , I) O
('l I'n powder was cooled with Tri-ice for 2 hours and then compressed into tablets.The uncoated tablets were left at 60°C for 48 hours.The result was 146 g/g. .1)00,
oof).

On the other hand, the number of Pyftothacterium emitted by m is G4.000 per g.
．． (G O'C as a powder without compressing the 100% powder into a tablet.
Result of drawing after leaving it inside for 24 hours; 3 per gram
It was 1.000.

The flute method for Hyphytobacterium uses BL medium,
Cultured for 72 hours at 37°C by steel wool method.
Calculated after

Fruit V15 Bifidobacterium (Bifidobacterium and others) were mixed with the same raw materials as Experiment 3, and the initial number of Bifidobacterium was 89.000 per g.
000 powder was compressed at room temperature and the uncoated tablets were rounded and the result was 22,000. There was OnO.

On the other hand, the result of cooling tableting was Hyphitobacterium ↓
Hit 121. The number of Hyphytobacterium resulting from room temperature coating of elementary S constant of OOO,000 is:
(10, f') 00°000, the number of Hyphytobacterium in the old nest of the cool-coated male is 109° per 3
There was oo, ooo.

Example 1 4.21 kg of powder containing 3% each of Antophilus, Faecalis and Hyphitobacterium
, non-acid resistant 7-mirase, protease, lipase mixture 4.8kg, plant j & fiber 16.84kg, calcium hydrogen phosphate 3.36J, lactose 7.84kg, crystalline cellulose 4.21kg, hazelnut butter 8.4kg ,
Weigh out 0.84 kg of stearin and magnenium,
Mix well and sieve to obtain 84.2 kg of powder for tabletting.

Tablet powder 8 = 1.2 was cooled to -20°C or less, and 320,000 uncoated tablets (80 kg) with a diameter of 8.5 mm and 250 B/tablet were made using a compression tablet machine.

3.2 kg of CAP (cellulose acetate phthalate) and 0.32 kg of ethyl phthalate were dissolved in 77 tons of 28.8 kg to prepare CAP i'i5 liquid.

Rotating 320,000 uncoated tablets pH 6I・pm, air volume 9 cubic meters/kuna, Jm 'J, '*r! ,! 1% J (,1(
: Next: J11 prepared coating pan;
Apply 1 coat of CAP coating after 1 minute of normal operation, and re-dry at 1.0'C or below to remove the solvent.
320,000 tablets of 0 m3/ml will be manufactured.

Powder for tableting made in Practical Example 1: 84.2 to 3 to 3 to water
5.8 kg was added and kneaded using a kneader. After drying at 40°C or less,
Sort and sieve to obtain 80 g of granules.

CAP (cellulose acetate phthalate) 3.2 J, phthal θ'2 ethyl 0. :32 to 77 tons to 28.8g, dissolve to make CA P,7i liquid. @La sot
<g was adjusted to a rotational speed of 16 r"rm, an IJI amount of 9 m3/min, and a blowing temperature of 40°C or less.Put it in a container and apply one coat of P coating to the top C.
83.2J of granules; 5゜ fruit = f tree 3 Streptococcus song: Lactohacilus revised edition: The final sedimentation of Hyphytobacterium was applied to the jejunum or eye oil of healthy people.
An example of bacterial flora ratio: 1: 10: 1000
0, these mixed beds 6') 6 containing powders 4.2
1 kg, non-acid resistant 7 mirror 7, protease, lipase mixture - 1,8 kg, vegetable fiber 16.84 kg,
Calcium hydrogen phosphate 3.36kg, lactose 7.84kg
, crystalline cellulose ↓ 21 +
1)) Litori, mix first, sieve to obtain powder for tableting 84.2 to 3. After cooling this material to below -10-C, it was compressed into 8.5 mmtM, 250
m3/320,000 uncoated tablets (Br) (,0 cleared.

Separately, 3.2 kg of cellulose acetate phthalate and 0.32 kg of ethyl phthalate were dissolved in A7TONE 2R [3].

320,000 uncoated tablets, rotation speed 16+, pH+-air volume 9 cubic Song/
Sprinkle 1 coat of corner ink using the usual method in a coating pan kept at a power transmission temperature of 40'C or less, dry it,
320,000 coated tablets of 260 mg/tablet will be manufactured.

Experiment 6 Take the 6 tablets you scraped in step 1 and crumble them.
Place each book into the glass tube of the tester, and add 1 part of artificial gastric juice (2.08 parts of thorium chloride, 21.0 parts of diluted hydrochloric acid, and 1 part of water).
is 00O. This I) H of α is approximately 1.2 and δ
reactor. ) Immerse the tester in a beaker containing about 900ml and pre-adjusted to 37±2°C and move it up and down for 1.120 minutes A2
After 60 minutes of observation, all six samples were found to have disintegrated, or because the film had opened, peeled off, or been damaged, and none of them showed any release of the drug contents. After gently pulling up the glass tube, place the artificial intestine 1i (o, 2ki, I) in a beaker with controlled temperature and liquid volume.
Add 211 Bml of 0.2N sodium hydroxide test II and water to 250ml of potassium dihydrogen phosphate test solution and make 11
)00ml. The second moat is a transparent bamboo color, and its 1) H is approximately 6°8. ), and when the auxiliary board was inserted and the granules were moved up and down for 60 minutes, all of them were dissolved and no residue from Test 14 was found in the No. 1 glass tube. Sieve with a whistle, remove 0.10 g each of the residue on the top, and put the auxiliary tube into the glass tube of the tester, fixing it at the bottom.
2 was used for 60 minutes of vertical movement and then observed. As a result, the number of particles falling from the mesh of the tester was about 15 tons, which was within the range of 2. After gently lifting the tester, check the temperature and liquid volume:
After immersing the beaker in the artificial LLI solution in Section A and moving it up and down for 30 minutes, no sample residue was found in the auxiliary tube.

Experiment 8 Inoculation was carried out under the same conditions as in Experiment 1. The inoculation results showed that the number of viable bacteria per gram was 100.000 for the control (physiological saline treated product, however, 2 in Experiment 1 was diluted with 1 gram), and 1 for the tablet in Example 1.
00.000, 9 for the same tablet before artificial treatment and treated with intestinal drops
8.000, 99.000 for the granules of Example 2,
It was 98,000 for the same granules before artificial treatment and intestine Iα treatment.

The ring image results for Example 1 and 3 were 200.000 for the control (physiological saline implantation) and 1 for the tablet before artificial preparation and intestinal fluid treatment.
It was 99,000.

From the above, it has been found that useful bacteria are hardly killed by the artificial stomach treatment of products used in the tablet and granule process.

Effects of the Invention As a result of the completion of the present invention as described above, the amount of microorganisms used in this production has improved f+' efficiency compared to the previous technology, and from this aspect as well, the cost has been reduced.

Experiment 9 ¥1+'ui lf'l: A tasting test was conducted on the coated tablets manufactured in 3. Seven men and women aged 20-5 F) in normal health were given the tablets.
After 3 days, 1 tablet of each was sampled. After 2 to 5 days, 6 people had a slight feeling of bloating in their intestines, and their farts became B1.

Claims (1)

[Scope of Claims] 1. A preparation for internal use with useful bacteria, characterized in that it contains a powder of useful intestinal bacteria including lactic acid bacteria and an enzyme as a solid agent, and is coated with a coating agent. 2. The useful bacterial internal preparation according to claim 1, wherein the solid preparation is a granule. 3. The useful oral preparation according to claim 1, wherein the solid preparation is a tablet. 4. A method for coating a solid preparation for internal use with useful bacteria, which is characterized by selecting a solvent for the coating agent that has no bactericidal or antibacterial properties, and drying at 40°C or lower. 5. The coating method according to claim 4, wherein the solid preparation for internal use is granules. 6. The coating method according to claim 4, wherein the solid preparation for internal use is a tablet. 7. A method for compressing tablets for internal use with useful bacteria, which comprises compressing the tableting powder after cooling it to 0°C or lower. 8. A method for granulating useful bacteria for internal use, which comprises cooling the granule mixture to 0° C. or lower before granulating it.