GB2217703A - Microbial products - Google Patents
Microbial products Download PDFInfo
- Publication number
- GB2217703A GB2217703A GB8907879A GB8907879A GB2217703A GB 2217703 A GB2217703 A GB 2217703A GB 8907879 A GB8907879 A GB 8907879A GB 8907879 A GB8907879 A GB 8907879A GB 2217703 A GB2217703 A GB 2217703A
- Authority
- GB
- United Kingdom
- Prior art keywords
- cure
- extract
- treatment
- stenohalis
- therapeutic composition
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 239000013586 microbial product Substances 0.000 title claims abstract description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 18
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 16
- 241000590020 Achromobacter Species 0.000 claims abstract description 8
- 239000000203 mixture Substances 0.000 claims description 12
- 230000001225 therapeutic effect Effects 0.000 claims description 7
- 208000000655 Distemper Diseases 0.000 claims description 6
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 5
- 238000000605 extraction Methods 0.000 claims description 5
- 238000000034 method Methods 0.000 claims description 5
- 208000004232 Enteritis Diseases 0.000 claims description 4
- 208000006454 hepatitis Diseases 0.000 claims description 4
- 231100000283 hepatitis Toxicity 0.000 claims description 4
- 241000282324 Felis Species 0.000 claims description 3
- 208000036142 Viral infection Diseases 0.000 claims description 3
- 238000011534 incubation Methods 0.000 claims description 3
- 239000011780 sodium chloride Substances 0.000 claims description 3
- 230000009385 viral infection Effects 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 239000002552 dosage form Substances 0.000 claims 3
- 239000003937 drug carrier Substances 0.000 claims 1
- 201000010099 disease Diseases 0.000 abstract description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 2
- 230000003612 virological effect Effects 0.000 abstract 1
- 239000000047 product Substances 0.000 description 9
- 239000002244 precipitate Substances 0.000 description 7
- 239000006228 supernatant Substances 0.000 description 7
- 230000000694 effects Effects 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- 206010012735 Diarrhoea Diseases 0.000 description 3
- 206010047700 Vomiting Diseases 0.000 description 3
- 208000014058 canine distemper Diseases 0.000 description 3
- 239000012153 distilled water Substances 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 238000004393 prognosis Methods 0.000 description 3
- 241000894006 Bacteria Species 0.000 description 2
- 241000282326 Felis catus Species 0.000 description 2
- 230000001580 bacterial effect Effects 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 239000012266 salt solution Substances 0.000 description 2
- 108010082126 Alanine transaminase Proteins 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 241000237074 Centris Species 0.000 description 1
- 208000002613 Feline Panleukopenia Diseases 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 206010019799 Hepatitis viral Diseases 0.000 description 1
- 241001662043 Icterus Species 0.000 description 1
- 206010023126 Jaundice Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 102000006382 Ribonucleases Human genes 0.000 description 1
- 108010083644 Ribonucleases Proteins 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 1
- 208000022531 anorexia Diseases 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 230000005875 antibody response Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 206010061428 decreased appetite Diseases 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 201000006549 dyspepsia Diseases 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 238000000703 high-speed centrifugation Methods 0.000 description 1
- 239000002799 interferon inducing agent Substances 0.000 description 1
- 238000009533 lab test Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000003908 liver function Effects 0.000 description 1
- 238000000464 low-speed centrifugation Methods 0.000 description 1
- 206010025482 malaise Diseases 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- KSSNXJHPEFVKHY-UHFFFAOYSA-N phenol;hydrate Chemical compound O.OC1=CC=CC=C1 KSSNXJHPEFVKHY-UHFFFAOYSA-N 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000013535 sea water Substances 0.000 description 1
- 239000013049 sediment Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000011287 therapeutic dose Methods 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- 229960005486 vaccine Drugs 0.000 description 1
- 201000001862 viral hepatitis Diseases 0.000 description 1
- 238000003809 water extraction Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/66—Microorganisms or materials therefrom
- A61K35/74—Bacteria
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Molecular Biology (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Abstract
A water soluble and ethanol insoluble extract of a microbial product obtained by the cultivation of Achromobacter stenohalis is used to combat viral diseases.
Description
MICROBIAL PRODUCTS
BACKGROUND OF THE INVENTION
In my Canadian Patent 915,106, I described a microbial product derived from Achromobacter stenohalis which had antiviral activities with a treatment of
Myxovirus such as pup's distemper and was capable of suppressing the growth of tumors. The product was produced by cultivating the bacterium in a saline solu tion. This product has been used commercially in Japan for many years with great success. With respect to parvoviral enteritis in puppies and panleucopenia in cats, in cure rates in the range of 60-70% were achieved when the microbial product was administered for one week or more.
Some published studies on the use of the microbial product of the Canadian patent can be found in
Okuda, Studies on the Treatment of Canine Distemper
Like Disease With Domon, Jui Chikusan Shimpo (Journal of Veterinary Medicine) (Tokyo), No. 482:1217-1219; Id.
No. 495:545-550; Shibani et al., Studies on the Treatment of Canine Distemper with Domon-L, Jui Chikusan
Shimpo, No. 498:725-729; Samejima et al., Experiment on the Antibody Response of Dogs Injected With Distemper
Live Vaccine to Administration With Domon-L; and
Kajiyama et al., Studies on the Treatment of Canine
Distemper With Domon-L, Jui Chikusan Shimpo, No. 500:811. It has been theorized that the product may stimulate the production of a neutralizing antibody or may possess activity as an interferon inducer.
It has now been discovered that a water soluble, ethanol insoluble extract fraction of the microbial product of the Canadian patent exhibits a greater spectrum of activity. For example, cure rates for puppies' parvoviral enteritis and feline panleucopenia of 100% have been obtained with the administration of the new extract for three days or less. It has been found useful in the treatment of human hepatitis.
It is accordingly the object of this invention to provide a new microbial product which is useful for the treatment of viral infections in man and animals. This and other objects of the invention will become apparent to those of ordinary skill in this art from the following detailed description.
SUMMARY OF THE INVENTION
This invention relates to a microbial product derived from a strain of Achromobacter stenohalis which product is water soluble and ethanol insoluble and to the use thereof in treating viral infections.
DESCRIPTION OF THE INVENTION
The bacterium Achromobacter stenohalis, from which the microbial product of this invention is derived, has been isolated from seawater, marine mud and marine phytoplankten. A preferred strain is ATCC 21710. The identity of the Achromobacter stenohalis is described in detail in my aforementioned Canadian patent.
The cultivation of the bacterium can be carried out as set forth in my aforementioned Canadian patent. Thus, the Achromobacter stenohalis is cultivated in a saline medium which may contain, optionally, a nutrient such as glucose and pepton. While I previously preferred a salt concentration of 1.5 to 2.5%, and incubation at 25-360C for 24-48 hours, I now preferred to use about 3.5% salt solution and one hour of incubation at a higher temperature of about 560C.
Nevertheless, the general conditions which I described in my prior patent can be used if so desired.
The use of a freeze-thaw cycle to remove slime from the culture broth described in my prior patent can be used but I now prefer simply to subject the broth to sonification, separate the precipitate from the supernatant and subject the supernatant to dialysis against distilled water. After filtering off any remaining sediment, the dialyzed supernatant can be lypholized if desired or it can be directly subjected to the extraction procedure.
To prepare the liquid for the extraction, it is first subjected to a low-speed centrifuge (up to 7,500 rpm and preferably about 5,000 rpm), the precipitate and supernatant separated, the supernatant subjected to a high-speed centrifuge (above 9,000 rpm and preferably about 12,000 rpm) and the supernatant and precipitate separated. Centrifugation periods of 15 to 60 minutes are normally used. The high-speed centri fuge precipitate can, if desired, be washed with water and is then subjected to the well-known Westphal's phenol extraction.
In the phenol-water extraction, the bacterial precipitate is suspended in water at about 5O to 700C, 90% phenol at the same temperature is added with vigorous stirring and then the mixture is maintained at elevated temperatures for a period of time. I prefer to effect the mixing at about 550C for 30 minutes followed by adding an equal volume of water and then maintaining the mixture in 60 for an additional 30 minutes. The mixture is cooled to ambient temperature followed by separating the phenol and water, for example by subjecting the mixture to centrifugation. The water extract is dialyzed against distilled water to remove traces of phenol and small amounts of low molecular weight bacterial substances.An RNA-free extract is prepared by)subjecting the dialyzed water extract to
RNase followed by three courses of very high-speed centrifugation (preferably 100,000g) for three hours.
The precipitate is then suspended in a salt solution, for example 0.5M NaCI which is mixed with ethanol, preferably at a weight of 1:10 and 1:20 maintained at about 40C for one or two hours. The mixture is subjected to low speed centrifugation, the resulting precipitate separated from the supernatant and suspended in water and dialyzed against distilled water. The resulting water soluble, ethanol insoluble extract can be used as is or, if desired, can be lypholized.
The microbial extraction products of the present invention can be used for preparing suitable therapeutic compositions in any form suitable for their application as is well known in the art. While the particular dosage is best determined by the attending clinician or veterinarian, in general the therapeutic dose will be in the range of about 5-350, preferably about 6-320 microgram of extract per kilogram host body weight.
In order to demonstrate the enhanced activity of the extract of the present invention compared to the microbial product of my Canadian patent, a therapeutic composition was prepared by dissolving one milligram of the product in one ml. of dissolved water and inoculating puppies suffering with parvoviral enteritis and cats suffering with feline panleucopenia once per day, subcutaneously, with a dosage of 1 ml of the solution.
The results were set forth in the following tables.
S Y M P T O M S NO. SEX AGE TEMPERATURE DIARRHEA EMESIS WBC TREATED TIMES PROGNOSIS 1 M 3 yrs. 39.5 C **** *** 2600 5 cure 2 F 2 yrs. 40.2 C **** **** 2200 4 cure 3 M 1 yr. 40.5 C **** **** 2600 4 cure 4 F 1 yr. 40.5 C **** *** 5200 4 cure 5 F 1 yr. 40.8 C **** **** 4200 4 cure 6 F 4 yrs. 40.0 C **** **** 5300 5 cure 7 M 3 yrs. 40.7 C **** **** 4300 4 cure 8 F 1 yr. 41.0 C **** **** 4600 3 cure 9 M 4 mos. 40.0 C **** **** 5000 5 cure 10 F 2 yrs. 39.1 C **** **** 3300 4 cur@ 11 M 2 yrs. 39.8 C **** **** 2200 4 cure 12 F 10 yrs. 40.3 C **** **** 4200 4 cure 13 F 7 yrs. 39.0 C **** **** 4000 2 cure 14 M 5 mos. 40.3-40.8 C **** **** 3400-3800 5 cure 15 F 1.5 yrs. 40.3 C **** **** 5500 5 cure 16 F 2 yrs. 40.7 C **** **** 6200 4 cure 17 M 1 yrs. 40.0 C **** **** 5100 4 cure TABLE NO. 1 - He@@orrhaqic entritis of Puppies NO.1
S Y M P T O M S No. SEX AGE TEMPERATURE DIARRHEA EMESIS WBC TREATED TIMES PROGNOSIS 18 F 14 yrs. 40.6 C **** **** 7400 4 cure 19 F 4 yrs. 39.5 C **** **** 2800 6 cure 20 F 2 yrs. 41.0 C **** **** 4500 4 cure 21 M 5 yrs. 39.7 C **** **** 5000 7 cure 22 M 4 yrs. 39.9 C **** *** 6200 4 cure 23 M 5 yrs. 39.5 C **** *** 5000 7 cure 24 F 1 yr. 40.1 C **** **** 7000 4 cure 25 M 9 yrs. 41.0 C **** **** 3800 5 cure TABLE NO. l - Hemmorrhaqic entritis of Puppies NO. 2
S Y M P T O M S TREATED No. SEX AGE TEMPERATURE DIARRHEA EMESIS WBC TREATED MEIHOD TIMES PROGNOSIS LPS 0.5ml, 1 M 1 yr. 40.0 C **** **** 2400 100 ml, ABPC 4 cure 2 M 1 yr. 40.0 C **** **** 4200 " 5 cure 3 M 4 yrs. 40.0 C **** **** 6000 " 1 cure 4 F 7 yrs. 40.0 C **** **** 2700 " 2 cure 5 M 1 yr. 40.0 C **** **** 1200 " 3 cure 6 M 3 yrs. 39.5 C **** **** 1800 " 5 cure 7 F 3 yrs. 39.2 C **** **** 3100 " 2 cure 8 F 5 mos. 40.0 C **** **** 2700 " 4 cure 9 M 1 yr. 40.3 C **** **** 4100 " 4 cure 10 M 3 yrs. 39.3 C **** **** 6800 " 5 cure 11 F 1 yr. 39.7 C **** **** 4100 " 3 cure TABLE NO. 2 - Feline FPL (Feline Panleukopenia) In a clinical demonstration, 60 cases of acute viral hepatitis (Type A - 16 cases onset seven to ten days; Type Non-A, Non-B - 14 cases; Type B - 30 cases onset two to three weeks) were treated by a double blind technique receiving injections of 1 ml. of physiological saline either with or without 0.5 mg. of the product. For Type A, the dosage schedule was one injection per day for the first week and then one injection every other day for the following two weeks.
For Type B, the dosage schedule was once a day for eight weeks. The clinical symptoms were a general malaise, anorexia, icterus and dyspepsia and the diagnosis was confirmed by laboratory tests. For the Type A patients, all clinical symptoms appeared after two weeks of treatment and hepatomegaty became normal after three weeks of treatment. The control group for Type A hepatitis began to recover little by little after the fourth week of treatment. The six cases of Non-A-Non-B treated with the product became normal after two to three weeks of treatment while in the control group, seven recovered after 5 weeks of treatment and the remaining member recovered after the sixth week of treatment.With respect to the Type B hepatitis, fourteen of the product treated patients had lost all clinical symptomology after three weeks of treatment and the remaining case took five weeks while the control group had ten members which eliminated the clinical symptoms as late as five weeks after treatment and one which did not lose the clinical symptoms after the eight weeks of treatment.With regard to the liver function, the time required for the SGPT to become normal is set forth in the following table.
Cases 2 weeks 3 weeks 3 to 5 )tre than weeks 5 weeks Type A 4 2 2 0 0 p R o NANB 6 1 1 4 0 D U C Type B 15 4 5 6 0 T Total 25 7 8 10 0 Type A 12 0 2 7 3 C 0 N NANB 8 0 3 3 2 T R o Type B 15 1 3 12 9 L Total 35 . 1 8 12 14
Various changes and modifications can be made in the invention described above without departing from the spirit and scope of the invention. The embodiments described herein were set forth for the purpose of illustration only.
Claims (10)
1. A water soluble and ethanol insoluble extract of a microbial product obtained by the cultivation of Acirarcbacter stenohalis.
2. A therapeutic composition comprising the extract of claim 1, in combination with a pharmaceutically acceptable carrier.
3. A therapeutic composition comprising the extract of claim 1, in combination with a veterinary acceptable carrier.
4. A therapeutic composition according to claim 2 or 3, in dosage form suitable for use in the treatment of viral infections.
5. A therapeutic composition according to claim 2, in dosage form suitable for the treatment of human hepatitis.
6. A therapeutic composition according to claim 3, in dosage form suitable for use in the treatment of pup distemper, pup parvoviral enteritis or feline panleucopenia.
7. A method for obtaining the extract of claim 1 comprising incubating Achrarobacter stenohalis in a saline medium comprising about 3.5% sodium chloride, and then applying
Westphal's phenol extraction technique.
8. The method according to claim 7, wherein the incubation period is about one hour at about 560C.
9. A water soluble and ethanol insoluble extract of a microbial product obtained by the cultivation of Achromobacter stenohalis substantially as hereinbefore described.
10. A method for producing a water soluble and ethanol insoluble extract of a microbial product obtained by the cultivation of Achromobacter stenohalis substantially as
hereinbefore described.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US18294388A | 1988-04-18 | 1988-04-18 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| GB8907879D0 GB8907879D0 (en) | 1989-05-24 |
| GB2217703A true GB2217703A (en) | 1989-11-01 |
| GB2217703B GB2217703B (en) | 1991-11-13 |
Family
ID=22670725
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB8907879A Expired - Lifetime GB2217703B (en) | 1988-04-18 | 1989-04-07 | Therapeutic microbial product extracted from achromobacter stenohalis. |
Country Status (2)
| Country | Link |
|---|---|
| GB (1) | GB2217703B (en) |
| IT (1) | IT1234390B (en) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS63316738A (en) * | 1987-06-19 | 1988-12-26 | Kunitoshi Cho | Immunostimulant |
| JPH07679A (en) * | 1993-06-15 | 1995-01-06 | Hitachi Ltd | Dehydration control device for fully automatic washing machines |
-
1989
- 1989-04-07 GB GB8907879A patent/GB2217703B/en not_active Expired - Lifetime
- 1989-04-14 IT IT8920140A patent/IT1234390B/en active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS63316738A (en) * | 1987-06-19 | 1988-12-26 | Kunitoshi Cho | Immunostimulant |
| JPH07679A (en) * | 1993-06-15 | 1995-01-06 | Hitachi Ltd | Dehydration control device for fully automatic washing machines |
Also Published As
| Publication number | Publication date |
|---|---|
| IT8920140A0 (en) | 1989-04-14 |
| GB2217703B (en) | 1991-11-13 |
| GB8907879D0 (en) | 1989-05-24 |
| IT1234390B (en) | 1992-05-18 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PCNP | Patent ceased through non-payment of renewal fee |
Effective date: 19930407 |