ANTI-INFLAMMATORY PHARMACEUTICAL COMPOSITION COMPRISING PROBIOTICS AND ANTIBIOTICS, AND METHOD USING SAME

Abstract

This application relates to a pharmaceutical composition for anti-inflammation, including a probiotic and an antibiotic, and a method of preventing or treating inflammation by using the same. In one aspect, the method includes locally administrating a probiotic and an antibiotic to an inflamed area of a subject.

Claims

1. A method of preventing or treating inflammation, the method comprising locally administrating a probiotic and an antibiotic to an inflamed area of a subject.

2. The method of claim 1, wherein the probiotic is a bacterium of a genus selected from the group consisting of the genus Lactobacillus, the genus Lactococcus, the genus Bacillus, the genus Enterococcus, the genus Streptococcus, the genus Bifidobacterium, the genus Pediococcus, and the genus Saccaromyces.

3. The method of claim 2, wherein the bacterium of the genus Lactobacillus is a bacterium of a species selected from the group consisting of Lactobacillus casei (L. casei), Lactobacillus acidophilus (L. acidophilus), Lactobacillus gasseri (L. gasseri), Lactobacillus delbrueckii ssp bulgaricus (L. delbrueckii ssp bulgaricus), Lactobacillus helveticus (L. helveticus), Lactobacillus fermentum (L. fermentum), Lactobacillus paracasei (L. paracasei), Lactobacillus plantarum (L. plantarum), Lactobacillus reuteri (L. reuteri), Lactobacillus rhamnosus (L. rhamnosus), and Lactobacillus salivarius (L. salivarius).

4. The method of claim 2, wherein the bacterium of the genus Bacillus is a bacterium of a species selected from the group consisting of Bacillus subtilis (B. subtilis), Bacillus coagulans (B. coagulans), Bacillus indicus (B. indicus), Bacillus clausii (B. clausii), Bacillus laterosporus, and Bacillus licheniformis (B. licheniformis).

5. The method of claim 2, wherein the bacterium of the genus Enterococcus is a bacterium of a species selected from the group consisting of Enterococcus faeciurn (E. faecium) and Enterococcus faecalis (E. faecalis).

6. The method of claim 1, wherein the antibiotic is selected from the group consisting of a β-lactam antibiotic, a tetracycline antibiotic, an aminoglycoside antibiotic, a macrolid antibiotic, a glycopeptide antibiotic, a lincosamide antibiotic, and a quinolone antibiotic.

7. The method of claim 6, wherein the β-lactam antibiotic is selected from the group consisting of a penicillin antibiotic, a cephalosporin antibiotic, and a monobactam antibiotic.

8. The method of claim 7, wherein the cephalosporin antibiotic is selected from the group consisting of cefaclor, ceftazidime, cefoperazone, cefotaxime, ceftizoxime, ceftriaxone, cefepime, cefpirome, cefozopran, ceftaroline, ceftolozane, and ceftobiprole.

9. The method of claim 6, wherein the tetracycline antibiotic is selected from the group consisting of doxycycline, tetracycline, chlortetracycline, oxytetracycline, demeclocycline, minocycline, lymecycline, methacycline, rolitetracycline, and tigecycline.

10. The method of claim 1, wherein the pharmaceutical composition is for preventing or treating inflammation is caused by infection with a bacterium, a fungus, or a combination thereof.

11. The method of claim 10, wherein the bacterium is an antibiotic-resistant bacterium selected from the group consisting of methicillin-resistant Staphylococcus aureus (MRSA), methicillin-sensitive Staphylococcus aureus (MSSA), vancomycin-resistant S. aureus (VRSA), an extended-spectrum beta-lactamase (ESBL) bacterium, vancomycin-resistant Enterococcus (VRE), multidrug-resistant Acinetobacter baumannii (MRAB), multidrug-resistant Pseudomonas aeruginosa (MRPA), and carbapenem-resistant enterobacteriaceae.

12. The method of claim 1, wherein the inflammation is associated with a disease selected from the group consisting of otitis media, acute sinusitis, chronic sinusitis, pharyngitis, rhinitis, dermatitis, atopic dermatitis, bacterial infection or inflammation after surgery, osteitis, osteomyelitis, otitis externa, necrotizing otitis externa, diabetic foot ulcer, intractable wound infection, inflammation in an abdominal cavity contaminated with feces, bacterial infection or inflammation at a site of insertion of foreign matter, and intractable infectious diseases.

13. The method of claim 1, wherein the method is for single administration or individual administration.

14. The method of claim 1, wherein the method is an external preparation, drop, or a combination thereof.

15. (canceled)

16. The method of claim 1, wherein the probiotic and the antibiotic are simultaneously or sequentially administered.

Description

BRIEF DESCRIPTION OF DRAWINGS

[0029] FIG. 1A illustrates a result sheet for the examination of a microorganism in pus collected from otitis media patient 1, and FIG. 1B illustrates images of the inner ear of patient 1 before/after treatment.

[0030] FIGS. 2 to 7 are images of the inner ears before/after treatment of patient 2 to patient 7, respectively.

[0031] FIG. 8A illustrates inner ear images showing the eardrum of an otitis media patient before treatment, FIG. 8B illustrates images of the inner ears after treatment with cefaclor and lockstar capsules, FIG. 8C illustrates images of the inner ears after treatment with cefaclor and medilac-S capsules, and FIG. 8D illustrates final images of the inner ears after 1 week (F1: the inner ear without a lesion, F2: the inner ear with a lesion).

[0032] FIG. 9A is an inner ear image showing the eardrum of an otitis media patient before treatment, and FIG. 9B is an image of the inner ear of an otitis media patient after treatment with lockstar and doxycycline.

[0033] FIG. 10A illustrates images showing the nasal cavities of a sinusitis patient before treatment, and FIG. 10B illustrates images of the nasal cavities of a sinusitis patient after treatment with lockstar and cefaclor (F1: the nasal cavity without a lesion, F2: the nasal cavity with a lesion).

MODE OF DISCLOSURE

[0034] Hereinafter, the present disclosure will be described in further detail with reference to the following examples. However, these examples are for illustrative purposes only and are not intended to limit the scope of the present disclosure.

EXAMPLE 1

Confirmation of Inflammation Treatment Effect of Composition Including Lactobacillus Strain and Antibiotic

[0035] To confirm whether a composition in which an antibiotic and a Lactobacillus strain as a probiotic are mixed is effective in treating inflammation, the efficacy was evaluated clinically.

[0036] First, the contents of 1 capsule of ramnos for oral use (Han Wha Pharma Co., Ltd., ingredient name: 250 mg of a freeze-dried culture of Lactobacillus casei var. Rhamnosus) and 1 capsule of fronclor (Han Wha Pharma Co., Ltd., ingredient name: 262 mg of cefaclor hydrate) were mixed in a number ratio of 1:1, and physiological saline was added to prepare about 1.5 ml of a mixture.

[0037] Case 1) Patient 1 (male/59 years old)

[0038] The patient had been suffering from otitis media for more than several years because there was no treatment effect even when the patient took antibiotics including cefaclor at other hospitals. Pus was collected from the ear of the patient, and a microorganism in the pus was examined. The microorganism examination results are illustrated in FIG. 1A.

[0039] As illustrated in FIG. 1A, the patient was infected with Staphylococcus aureus, and the bacterium was methicillin-resistant Staphylococcus aureus (MRSA), which has resistance to an antibiotic. Thus, it was confirmed that the patient was infected with a multidrug-resistant bacterium.

[0040] The prepared mixture was injected into an ear of the patient via a syringe or added dropwise thereinto to be flowed into the ear. After this treatment was repeated three times at intervals of one to three days, a lesion was confirmed. Images before/after treatment are illustrated in FIG. 1 B. As illustrated in FIG. 1 B, fungi and ooze on the left side disappeared, from which it was confirmed that inflammation was treated. In addition, there was no recurrence even after several months after treatment, from which it was determined that the inflammation was completely cured.

[0041] Case 2) Patient 2 (female/90 years old)

[0042] The patient was diagnosed with otitis media and had fungi and ooze in the inner ear.

[0043] As described above, the prepared mixture was injected with a syringe or added dropwise to be flowed into the ear. After this treatment was repeated about five times, a lesion was confirmed. Images before/after treatment are illustrated in FIG. 2. As illustrated in FIG. 2, it was confirmed that fungi and ooze on the left side disappeared.

[0044] Case 3) Patient 3 (male/78 years old)

[0045] The patient was diagnosed with otitis media and had ooze and symptoms such as bubbles in the inner ear. The patient was infected with Staphylococcus aureus, and the bacterium was methicillin-sensitive Staphylococcus aureus (MSSA), which has resistance to an antibiotic.

[0046] As described above, the prepared mixture was injected with a syringe or added dropwise to be flowed into the ear. After this treatment was repeated three times, a lesion was confirmed. Images before/after treatment are illustrated in FIG. 3. As illustrated in FIG. 3, it was confirmed that ooze and symptoms such as bubbles on the left side disappeared.

[0047] Case 4) Patient 4 (female/59 years old)

[0048] The patient was diagnosed with otitis media, and had a lump of ooze in the inner ear.

[0049] As described above, the prepared mixture was injected with a syringe or added dropwise to be flowed into the ear. After this treatment was repeated 12 times at intervals of one to three days, a lesion was confirmed. Images before/after treatment are illustrated in FIG. 4. As illustrated in FIG. 4, it was confirmed that the lump of ooze on the left side disappeared.

[0050] Case 5) Patient 5 (male/77 years old)

[0051] The patient was diagnosed with otitis media, and had fungi and ooze in the inner ear. Through bacterial examination, Staphylococcus lugdunensis was confirmed, and this bacterium showed susceptibility to all antibiotics except for penicillin.

[0052] As described above, the prepared mixture was injected with a syringe or added dropwise to be flowed into the ear. After this treatment was repeated four times at intervals of one to three days, a lesion was confirmed. Images before/after treatment are illustrated in FIG. 5. As illustrated in FIG. 5, it was confirmed that fungi and ooze on the left side disappeared.

[0053] Case 6) Patient 6 (female/75 years old)

[0054] The patient was diagnosed with severe otitis media and necrotizing otitis externa, and had a lot of ooze in the inner ear.

[0055] About 1 ml of an extract, obtained from 1 g of 1 vial of ceftazidime injection (ceftazidime injection, UNION KOREA PHARM CO., LTD.) mixed with 3 ml of physiological saline, was mixed again with 1 capsule of ramnos (Han Wha Pharma Co., Ltd., ingredient name: 250 mg of a freeze-dried culture of Lactobacillus casei var. Rhamnosus) to prepare about 1.5 ml of a mixture.

[0056] The mixture was injected with a syringe or added dropwise to be flowed into the ear. After this treatment was repeated seven times at intervals of one to three days, ooze disappeared, but recurred after two days. Thus, the contents of 1 capsule of ramnos for oral use (Han Wha Pharma Co., Ltd., ingredient name: 250 mg of a freeze-dried culture of Lactobacillus casei var. Rhamnosus) and 1 capsule of fronclor (Han Wha Pharma Co., Ltd., ingredient name: 262 mg of cefaclor hydrate) were mixed in a number ratio of 1:1, and physiological saline was added to prepare about 1.5 ml of a mixture, and the mixture was injected into the middle ear cavity via the external auditory canal four times at intervals of one to three days. No oozing occurs any more. However, to eliminate any remaining bacteria, after two days, 1 ml of 1 vial of ceftazidime injection (1 g, ceftazidime injection, UNION KOREA PHARM CO., LTD.) mixed with 3 ml of physiological saline was injected alone into the ear.

[0057] After three days, clear ooze was observed, but not pus. Thus, the contents of 1 capsule of ramnos for oral use (Han Wha Pharma Co., Ltd., ingredient name: 250 mg of a freeze-dried culture of Lactobacillus casei var. Rhamnosus) and 1 capsule of fronclor (Han Wha Pharma Co., Ltd., ingredient name: 262 mg of cefaclor hydrate) were mixed in a number ratio of 1:1, and physiological saline was added to prepare about 1.5 ml of a mixture. The mixture was injected into the middle ear cavity via the external auditory canal three times at intervals of three days, and a lesion was confirmed.

[0058] Images before/after treatment are illustrated in FIG. 6. As illustrated in FIG. 6, a lot of stagnant ooze on the left side completely disappeared and a perforation in the eardrum was seen.

[0059] Case 7) Patient 7 (female/88 years old)

[0060] The patient was diagnosed with otitis media and had symptoms such as bubbles in the inner ear. The patient was infected with Staphylococcus aureus, and the bacterium was methicillin-sensitive Staphylococcus aureus (MSSA).

[0061] As described above, the prepared mixture was injected with a syringe or added dropwise to be flowed into the ear. After this treatment was repeated three times at intervals of one day, a lesion was confirmed. Images before/after treatment are illustrated in FIG. 7. As illustrated in FIG. 7, it was confirmed that ooze and symptoms such as bubbles on the left side disappeared.

EXAMPLE 2

Confirmation of Inflammation Treatment Effect of Composition Including Probiotic and Antibiotic

[0062] 2-1. Inflammation Treatment Effect of Probiotic and Cefaclor

[0063] To confirm whether other probiotics in addition to Lactobacillus casei var. Rhamnosus and cefaclor also have an inflammation treatment effect, a rockstar capsule for oral use (KOLON PHARMA, ingredient name: 100 mg of a freeze-dried culture of Lactobacillus casei var. Rhamnosus) and a medilac-S enteric capsule for oral use (Hanmi, Ingredient name: Bacillus subtilis and Enterococcis faecium) were prepared.

[0064] Physiological saline was added to a mixture of 1 capsule of rockstar and 1 capsule of fronclor to prepare about 3 ml of a mixture. As described in Example 1, the prepared mixture was injected into the middle ear of a patient with otitis media. As a result of follow-up of the patient with otitis media, it was confirmed that inflammation due to otitis media was ameliorated and the eardrum was also narrowed. Subsequently, the same process was repeated using the medilac-S capsule instead of the rockstar capsule.

[0065] Images showing the eardrum of a patient before treatment are illustrated in FIG. 8A, images after treatment with cefaclor and the rockstar capsule are illustrated in FIG. 8B, and images after the subsequent treatment with cefaclor and the medilac-S capsule are illustrated in FIG. 8C, and the final images after one week are illustrated in FIG. 8D.

[0066] As illustrated in FIGS. 8A to 8D, it was confirmed that, through the combination of a probiotic and an antibiotic, a perforation in the eardrum was narrowed or completely closed, and inflammation disappeared.

[0067] 2-2. Inflammation Treatment Effect of Probiotic and Doxycycline

[0068] To confirm whether other combinations besides a probiotic and cefaclor also have an inflammation treatment effect, a rockstar capsule and doxycycline (doxyramycin capsules 100 mg, manufacturer: SINIL Pharmaceutical Co., Ltd, seller: DongKoo Bio&Pharma Co., Ltd.) were prepared.

[0069] Physiological saline was added to a mixture of 1 capsule of rockstar and 1 capsule of doxycycline to prepare about 3 ml of a mixture. As described in Example 1, the prepared mixture was injected into the middle ear of a patient with otitis media.

[0070] An image showing the eardrum of the patient before treatment is illustrated in FIG. 9A, and an image after treatment with rockstar and doxycycline is illustrated in FIG. 9B.

[0071] As illustrated in FIGS. 9A and 9B, it was confirmed that, even when doxycycline, which is a different class from cefaclor, was used as an antibiotic, a perforation in the eardrum was narrowed or completely closed, and inflammation was treated.

EXAMPLE 3

Confirmation of Effect of Composition Including Probiotic and Antibiotic on Treating Sinusitis

[0072] To confirm whether a composition in which a probiotic and an antibiotic were mixed also has a therapeutic effect on other inflammations as well as otitis media, patients who also has sinusitis were selected from among patients with otitis media.

[0073] For the selected patients, the inside of a nose was washed in the same manner as in Example 1.

[0074] Images showing the nasal cavities of the patients before treatment are illustrated in FIG. 10A, and images after treatment with rockstar and cefaclor are illustrated in FIG. 10B.

[0075] As illustrated in FIGS. 10A and 10B, it was confirmed that symptoms of sinusitis completely disappeared by using a probiotic and an antibiotic.

[0076] As shown in Examples 1 to 3, it has been confirmed that a composition including a probiotic and an antibiotic is effective in the prevention or treatment of inflammation. Therefore, it has been confirmed that, in inflammation caused by bacterial or fungal infection, the inflammation can be prevented or treated by replacing the flora of bacteria or fungi with bacteria of probiotics and killing bacteria by using antibiotics.