CA1103165A - Process for the inactivation of viruses - Google Patents
Process for the inactivation of virusesInfo
- Publication number
- CA1103165A CA1103165A CA320,355A CA320355A CA1103165A CA 1103165 A CA1103165 A CA 1103165A CA 320355 A CA320355 A CA 320355A CA 1103165 A CA1103165 A CA 1103165A
- Authority
- CA
- Canada
- Prior art keywords
- ratio
- pharmaceutical
- terpenes
- parts
- plaster
- 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.)
- Expired
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N7/00—Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23C—DAIRY PRODUCTS, e.g. MILK, BUTTER OR CHEESE; MILK OR CHEESE SUBSTITUTES; MAKING THEREOF
- A23C9/00—Milk preparations; Milk powder or milk powder preparations
- A23C9/12—Fermented milk preparations; Treatment using microorganisms or enzymes
- A23C9/123—Fermented milk preparations; Treatment using microorganisms or enzymes using only microorganisms of the genus lactobacteriaceae; Yoghurt
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23C—DAIRY PRODUCTS, e.g. MILK, BUTTER OR CHEESE; MILK OR CHEESE SUBSTITUTES; MAKING THEREOF
- A23C9/00—Milk preparations; Milk powder or milk powder preparations
- A23C9/12—Fermented milk preparations; Treatment using microorganisms or enzymes
- A23C9/13—Fermented milk preparations; Treatment using microorganisms or enzymes using additives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/11—Aldehydes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/12—Ketones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
- A61K31/23—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin of acids having a carboxyl group bound to a chain of seven or more carbon atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/357—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having two or more oxygen atoms in the same ring, e.g. crown ethers, guanadrel
- A61K31/36—Compounds containing methylenedioxyphenyl groups, e.g. sesamin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/23—Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/54—Lauraceae (Laurel family), e.g. cinnamon or sassafras
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/67—Piperaceae (Pepper family), e.g. Jamaican pepper or kava
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/88—Liliopsida (monocotyledons)
- A61K36/899—Poaceae or Gramineae (Grass family), e.g. bamboo, corn or sugar cane
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/88—Liliopsida (monocotyledons)
- A61K36/906—Zingiberaceae (Ginger family)
- A61K36/9064—Amomum, e.g. round cardamom
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N1/00—Microorganisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
- C12N1/38—Chemical stimulation of growth or activity by addition of chemical compounds which are not essential growth factors; Stimulation of growth by removal of a chemical compound
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2710/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
- C12N2710/00011—Details
- C12N2710/10011—Adenoviridae
- C12N2710/10311—Mastadenovirus, e.g. human or simian adenoviruses
- C12N2710/10361—Methods of inactivation or attenuation
- C12N2710/10363—Methods of inactivation or attenuation by chemical treatment
Abstract
ABSTRACT
The invention relates to a pharmaceutical preparation for inacti-vating viruses within living human and animal organisms, by the use of a terpene obtainable, by steam distillation, from spice plants. The prepara-tion comprises one or more spice plant terpenes in admixture with a pharmaceutical-application carrier-substance in a ratio of between 1:100 and 20:100.
The invention relates to a pharmaceutical preparation for inacti-vating viruses within living human and animal organisms, by the use of a terpene obtainable, by steam distillation, from spice plants. The prepara-tion comprises one or more spice plant terpenes in admixture with a pharmaceutical-application carrier-substance in a ratio of between 1:100 and 20:100.
Description
~i~3i~5 The invention relates to a pharmaceutical preparation for inacti-vating viruses within living human and animal organisms, without producing cell damage, or other harmful secondary effects, in the organisms so treated.
The pharmaceutical preparation according to the invention is char-acterized by the use of a terpene, obtainable by steam distillation from spice plants, in a daily dosage of between 5 and 500 mg, preferably between 25 and 100 mg, to each 50 kg of the weight of the living organism.
It has been unexpectedly discovered that these terpenes have a virucidal action (i.e. a virus-damaging effect) in a concentration which is lower, by one or more powers of ten, than that at which these terpenes have toxic effects on living cells. This wide range provides an advantageous tolerance in dosage, thus allowing the terpenes to be used safely in animal and human medicine.
Since the terpenes may be obtained from spice plants which, for many years, have proven satisfactory for human and animal nutrition and have been found harmless in the amounts in question, it is to be expected that the amounts of terpene to be used according to the invention will pro-duce no seriously detrimental side effects.
According to the present invention, there is provided a pharma ceutical preparation for inactivating viruses within living human and ar~mal organisms, comprising one or more spice plant terpenes in admixture with a pharmaceutical-application carrier-substance in a ratio of between 1:100 and 20:100.
The following terpenes, which may be used separately or mixed with each other, have been found to be eminently satisfactory: black-pepper oil, cinnamon-~lower oil, cardamum oil, linalyl acetate, cinnamic aldehyde, ..
~.
,. - :. ,;,: . ,:...... . :
:
~ 3i6s safrol, carvone and cis/trans citralO
me pharmaceutical preparation according to the invention, for the purpose of inactivating viruses within living human and animal organisms, is produced from one or more of these terpenes obtained, by steam distilla-tion, from the parts of the spice plants which contain the relevant terpenes. me terpenes are then mixed with a pharmaceutical-application carrier-substance in a ratio of between 1:100 and 20:1000 me terpenes used may be obtained from spice plants by steam dis-tillation, as foIlows:
black-pepper oil: from the pips of the piper nigrum;
cinnamon-flower oil: from the blossoms of the cinnamonum~cassia;
cardamum oil: from the seeds of the elettaria cardamomum;
linalyl acetate: from the blossoms of the lavender;
cinnamic aldehyde: from the bark of the cinnamonum ceylanicum;
safrol: from the root of the sassafras;
carvone: from the fruit of the carum carvi, and cis/trans citral: from the leaves of the cymbopogon citratusO
These natural terpenes may also be replaced with identical synthetic terpenes, if they are available, but natural terpenes obtained from spice plants are preferredO
The results obtainable with the invention are determined by com-parison tests as follows:
Cell cultures were grown in various vessels, under optimal conditions, from permanent strains such as "Girardi Heart" (GH). "Flow 12000" (FL), "Intestine 407" (IN) and "Vero Kidney" (V~)~ forming on the b~*tom of each vessel a mat of cell culture containing about 0,25 mg of cell substance.
_ 2 -. .
:. . . :
, . ~ . .
11~3165 A suspension of virus particles of the Virus Adeno type 6 was also used.
For the total of eigh~ terpenes shown in Table 1, twenty cultures were prepared from each type of cell. The twenty cultures from each type of cell were treated with different amounts of the relevant terpene, as shown below.
The first two cell cultures received 10 mg of terpene per 10 kg of cell substance. The next two cell cultures received 104 mg of terpene per 10 kg of cell substance. The next two cell cultures received 10 mg of terpene per 10 kg of cell substance~ and so on to the last two of these twenty cell cultures which received 0~1 mg of terpene per 10 kg of cell substance. Thus two similar cell cultures were always treated with the same amount of the same terpene. One of these two similar cell cultures was left as it was for control purposes~ while the second was also inoculated, while still in the form of a virus suspension with 5 x 10 virus particles per 0,25 mg of cell substance. The other cell cultures and terpenes were dealt with accordingly.
The cell cultures thus treated were left standing and, after four and six days, they were examined microscopically for cell damage, the damage observed being grouped into four stages, as follows:
stage O signifying no damage stage 1 signifying loosened growth of the cell bonds stage 2 signifying that the cells had formed balls and become detached from the bottom of the vessel stage 3 signifying that the cell structures had been largely or completely destroyed.
_ 3 -. ..
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11~316S
It was found that inoculated cell structures which had been protected with a very small amount of terpene had reached stage 3 or 2, since the viruses had damaged the cellsO Inoculated cell structures con-taining a very large amount of terpene had also reached stage 3 or 2, since the cells had been damaged by the excess of terpene. However, cell cultures containing only a moderate amount of terpene were at stage 0, iOeO they had not been damaged. Thus the moderate amount of terpene damaged the viruses enough to protect the cells from attack, but did not damage the cells them-selves. Terpene concentrations at which the inoculated cell cultures, after four and six days, were at stage 0, with only a few at stage 1, produce adequate virus damage with no cell damage, and are given in Table 1.
The first column in Table 1 indicates the terpene used, column 2 gives the cell strains treated - abbreviated as indicated above, while column 3 gives the amount of terpene used, in mg/10 kg of treated cell substance, for the concentration range within which no substantial cell damage was observed (i.e. stage 0). This is the treatment range, which in each case extends over several powers of ten. Thus in the case of all of the terpenes given in Table I, the virucidal action sought occurs at a concentration which is lower, by several powers of ten, than the lowest concentration at which cell damage was observed, i.e. at which damage to the micro-organisms to be protected could occur.
. .
~- '',,' .
,:
~ 3~65 Table 1 Terpene Cell Substance Virucidal concentration Treated range over which no cell damage was observed ex-pressed in mg of terpene per 10 kg of treated cell substance _ Black-pepper oil GH 103 to 0.1 ~' FL 100 to Oo1 " IN 100 ^to 1 " VE 100 to 0.1 ; Cinnamon-Flower oil GH 103 to 0.1 " F~ 10 to 0.1 :: ~l IN 100 to 0.1 ~ " VE 100 to Oo1 :, '' ' _ Cardamum oil GH 100 to 1 " FL 100 to 1 ~ " IN 100 to 1 : ~ VE 100 to 10 :
.
, :: . " , " ,, -. - : .: ~. . .:
'' " ~
~ 3~65 Table 1 - Continued Terpen Cell Substance Virucidal concentration range Treated over which no cell damage was observed expressed in mg of terpene per 10 kg of treated cell substance _ _ _ Linalyl acetate GH 100 to 0~1 " F~ 100 to " IN 100 to " V~ 100 to Cinnamic aldehyde GH 100 to " FL 100 to " IN 100 to " VE 100 to Safrol GH 100 to " FL 100 to " IN 100 to 10 " VE 100 to _ CarvoneGH 100 to " F~ 100 to IN 100 to " VE 100 to _ _ _ _ cisltrans citral GH 10 to " FL 10 to " IN 100 to " VE 100 to ' ""
, .''~'.' . ' , . . ~
~13~6S
Example 1. (Injection solution).
50 g of black-pepper oil are dissolved in 2~ of 1,2-dihydroxypro-pane. The solution is sterilized for 50 minutes, at 121 C in an autoclave, is then cooled and placed in ampoules containing 2 g each.
One ampoule contains 50 mg of black-pepper oil which is an average daily dose for an adult weighing 70 kg for therapy and prophylaxis of influenza infections. For human and animal patients of another weight, the daily dose will be proportional to the patient's weight.
In this example, the ratio of terpene to 1,2 dihydroxy propane is as 2.5:100, but other mixture ratios are possible for injections solutions, from 1: 100 to S:100. However, the daily dose of injec~ion solution must then be adapted to the altered terpene content thereof.
xample 2. (Aerosol).
325 g of black-pepper oil are dissolved in 631,8 g of ether mixed with 1805,07 g of ethanol. 31,6 g of esters of castor-oil fatty acids with oxethylated glycerine and 210,6 g of caprylic/capric-acid triglyceride are mixed into this solution. 2.68 g of this mixture, and 2537 g of difluorodichloromethane, are introduced, as a propellant, into a spray-can having a capacity of 20 ccm. The spray-can is closed and comprises a metering valve which releases a predeter~ined amount of the mixture each time it is actuated, in the form of an aerosol, under the pressure from the difluoro-dichloromethane.
A metering valve of the correct size, correctly adjusted, ensures the release, at each actuation, of a single dose containing 6.5 mg of black-pepper oilO
For therapy and prophylaxis in the case of influenza infections, the aerosol is sprayed into the mouth or nose and is inhaledO For a 70 kg .:. , -, .. .
, :................. . . ,:
li~3~65 adult, a suitable daily dose is 8 spray portions, i.e. a total of 8 x 6.5 =
50 mg of black-pepper oil.
Skin areas affected by virus infections may also be treated with the aerosol, in which case seven spray portions each, containing 6.5 mg of black-pepper oil are applied to 50 cm of skin~
In this example, the ratio of terpene to aerosol substance is as 12:100, but other ratios are possible, from 5:100 to 20:100, the daily dose must be adapted to the altered terpene content of each spray portionO
Example 3. (Capsule) A capsule filling is produced from a mixture of 12.5 g of black-pepper oil and 12.5 g of cinnamon-flower oil, with 3 g of soya lecithin as an emulsifier. Each capsule contains 28 mg of this rnixture, the said capsule consisting of 87.5 mg of gelatine and 37.5 mg of glycerine.
For therapy and prophylaxis in the case of influenza infections, one to four of these capsules are administered each day orally to a 70 kg adult. If several capsules are administered, they should be spread over the day.
One capsule contains 25 mg of terpene, but this may be modified to between 10 and 50 g, in which case the daily dose must be adapted to the altered terpene content of the capsules.
Example 4. ~Stick) 1 g of black-pepper oil is mixed with a dimensionally stable carrier compound. ~is compound consists of 59084 g of white vaseline and 39.16 g of paraffin. ~his is mixed thoroughly with the terpene at 70 C, after which it is molded to form a stick and is hardened by coolingO
For local treatment, the stick is applied to the skin in such a manner as to distribute 1 ml of the stick compound - which in this example ' ' ..
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:
11~316S
contains 5 mg of terpene - over 50 cm of skin. mis may be repeated three times daily.
In this example, the ratio of terpene to carrier compound is as 1:100, but other ratios are possible, for example from 1:100 to 5:100.
Example 5. (Ointment).
3.2 g of hard paraffin and 86.8 g of white vaseline are heated to 60C and stirred togetherO 10 g of cinnamon-flower oil are added to the hot mixture. The mixture is then cooled and may be used as an ointment for local application. hbout 0.1 ml of the ointment - containing about 5 mg of terpene - are spread over 50 cm of skin surface. This may be repeated eight times daily.
The ratio of terpene in the paraffin/vaseline mixture in this example is as 11:100, but other ratios are also possible, for example from 5:100 to 20:100.
Example 6. (Plaster).
A vapour-proof plaster foil is made from a textile fabric by coating the bottom surface with a synthetic material. On the other side - the contact side - the plaster is coated to a depth of 1 mm with a compound made by mixing together 97 g of lead plaster(?)~ 9 g of yellow wax, 9 g of dammar, 10 g of colophonium, and 1 g of turpentineO mis mixture is heated to 100 C and is stirred until the molten mass no longer foams. 5 g of black-pepper oil are then stirred in, after which the compound is applied to the contact side of the plaster foil and is hardened by coolingO
~he contact side of the plaster is applied to the skin and is allowed to remain there for four hours. It may then be replaced with a fresh plaster.
In this example, the ratio of terpene to plaster compo~nd is as 4:100, but other ratios are possible, for example between 1:100 and 10:100~
.. _ _ g _ , .
: , :: . - : :
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,, ' ' - ' ~ ~ :
~1~316S
The preparation and treatments given in the foregoing examples make it possible to prevent or repress virus attacks, without any cell damage in the organism thus treated or any serious side-effects.
The examples given may be modified by replacing the terpene used with the same amount of another terpene :Erom Table I, or with a mixture of several such terpenes. In all of these cases, virucidal action is achieved without any unwanted side-effects.
The aforementioned micro-organisms are accessible to the public as follows:
1. Girardi Hear~ under CCL27 at ATCC (American Type Culture Collection)
The pharmaceutical preparation according to the invention is char-acterized by the use of a terpene, obtainable by steam distillation from spice plants, in a daily dosage of between 5 and 500 mg, preferably between 25 and 100 mg, to each 50 kg of the weight of the living organism.
It has been unexpectedly discovered that these terpenes have a virucidal action (i.e. a virus-damaging effect) in a concentration which is lower, by one or more powers of ten, than that at which these terpenes have toxic effects on living cells. This wide range provides an advantageous tolerance in dosage, thus allowing the terpenes to be used safely in animal and human medicine.
Since the terpenes may be obtained from spice plants which, for many years, have proven satisfactory for human and animal nutrition and have been found harmless in the amounts in question, it is to be expected that the amounts of terpene to be used according to the invention will pro-duce no seriously detrimental side effects.
According to the present invention, there is provided a pharma ceutical preparation for inactivating viruses within living human and ar~mal organisms, comprising one or more spice plant terpenes in admixture with a pharmaceutical-application carrier-substance in a ratio of between 1:100 and 20:100.
The following terpenes, which may be used separately or mixed with each other, have been found to be eminently satisfactory: black-pepper oil, cinnamon-~lower oil, cardamum oil, linalyl acetate, cinnamic aldehyde, ..
~.
,. - :. ,;,: . ,:...... . :
:
~ 3i6s safrol, carvone and cis/trans citralO
me pharmaceutical preparation according to the invention, for the purpose of inactivating viruses within living human and animal organisms, is produced from one or more of these terpenes obtained, by steam distilla-tion, from the parts of the spice plants which contain the relevant terpenes. me terpenes are then mixed with a pharmaceutical-application carrier-substance in a ratio of between 1:100 and 20:1000 me terpenes used may be obtained from spice plants by steam dis-tillation, as foIlows:
black-pepper oil: from the pips of the piper nigrum;
cinnamon-flower oil: from the blossoms of the cinnamonum~cassia;
cardamum oil: from the seeds of the elettaria cardamomum;
linalyl acetate: from the blossoms of the lavender;
cinnamic aldehyde: from the bark of the cinnamonum ceylanicum;
safrol: from the root of the sassafras;
carvone: from the fruit of the carum carvi, and cis/trans citral: from the leaves of the cymbopogon citratusO
These natural terpenes may also be replaced with identical synthetic terpenes, if they are available, but natural terpenes obtained from spice plants are preferredO
The results obtainable with the invention are determined by com-parison tests as follows:
Cell cultures were grown in various vessels, under optimal conditions, from permanent strains such as "Girardi Heart" (GH). "Flow 12000" (FL), "Intestine 407" (IN) and "Vero Kidney" (V~)~ forming on the b~*tom of each vessel a mat of cell culture containing about 0,25 mg of cell substance.
_ 2 -. .
:. . . :
, . ~ . .
11~3165 A suspension of virus particles of the Virus Adeno type 6 was also used.
For the total of eigh~ terpenes shown in Table 1, twenty cultures were prepared from each type of cell. The twenty cultures from each type of cell were treated with different amounts of the relevant terpene, as shown below.
The first two cell cultures received 10 mg of terpene per 10 kg of cell substance. The next two cell cultures received 104 mg of terpene per 10 kg of cell substance. The next two cell cultures received 10 mg of terpene per 10 kg of cell substance~ and so on to the last two of these twenty cell cultures which received 0~1 mg of terpene per 10 kg of cell substance. Thus two similar cell cultures were always treated with the same amount of the same terpene. One of these two similar cell cultures was left as it was for control purposes~ while the second was also inoculated, while still in the form of a virus suspension with 5 x 10 virus particles per 0,25 mg of cell substance. The other cell cultures and terpenes were dealt with accordingly.
The cell cultures thus treated were left standing and, after four and six days, they were examined microscopically for cell damage, the damage observed being grouped into four stages, as follows:
stage O signifying no damage stage 1 signifying loosened growth of the cell bonds stage 2 signifying that the cells had formed balls and become detached from the bottom of the vessel stage 3 signifying that the cell structures had been largely or completely destroyed.
_ 3 -. ..
- :, . . ~ , . : ,: - , .
11~316S
It was found that inoculated cell structures which had been protected with a very small amount of terpene had reached stage 3 or 2, since the viruses had damaged the cellsO Inoculated cell structures con-taining a very large amount of terpene had also reached stage 3 or 2, since the cells had been damaged by the excess of terpene. However, cell cultures containing only a moderate amount of terpene were at stage 0, iOeO they had not been damaged. Thus the moderate amount of terpene damaged the viruses enough to protect the cells from attack, but did not damage the cells them-selves. Terpene concentrations at which the inoculated cell cultures, after four and six days, were at stage 0, with only a few at stage 1, produce adequate virus damage with no cell damage, and are given in Table 1.
The first column in Table 1 indicates the terpene used, column 2 gives the cell strains treated - abbreviated as indicated above, while column 3 gives the amount of terpene used, in mg/10 kg of treated cell substance, for the concentration range within which no substantial cell damage was observed (i.e. stage 0). This is the treatment range, which in each case extends over several powers of ten. Thus in the case of all of the terpenes given in Table I, the virucidal action sought occurs at a concentration which is lower, by several powers of ten, than the lowest concentration at which cell damage was observed, i.e. at which damage to the micro-organisms to be protected could occur.
. .
~- '',,' .
,:
~ 3~65 Table 1 Terpene Cell Substance Virucidal concentration Treated range over which no cell damage was observed ex-pressed in mg of terpene per 10 kg of treated cell substance _ Black-pepper oil GH 103 to 0.1 ~' FL 100 to Oo1 " IN 100 ^to 1 " VE 100 to 0.1 ; Cinnamon-Flower oil GH 103 to 0.1 " F~ 10 to 0.1 :: ~l IN 100 to 0.1 ~ " VE 100 to Oo1 :, '' ' _ Cardamum oil GH 100 to 1 " FL 100 to 1 ~ " IN 100 to 1 : ~ VE 100 to 10 :
.
, :: . " , " ,, -. - : .: ~. . .:
'' " ~
~ 3~65 Table 1 - Continued Terpen Cell Substance Virucidal concentration range Treated over which no cell damage was observed expressed in mg of terpene per 10 kg of treated cell substance _ _ _ Linalyl acetate GH 100 to 0~1 " F~ 100 to " IN 100 to " V~ 100 to Cinnamic aldehyde GH 100 to " FL 100 to " IN 100 to " VE 100 to Safrol GH 100 to " FL 100 to " IN 100 to 10 " VE 100 to _ CarvoneGH 100 to " F~ 100 to IN 100 to " VE 100 to _ _ _ _ cisltrans citral GH 10 to " FL 10 to " IN 100 to " VE 100 to ' ""
, .''~'.' . ' , . . ~
~13~6S
Example 1. (Injection solution).
50 g of black-pepper oil are dissolved in 2~ of 1,2-dihydroxypro-pane. The solution is sterilized for 50 minutes, at 121 C in an autoclave, is then cooled and placed in ampoules containing 2 g each.
One ampoule contains 50 mg of black-pepper oil which is an average daily dose for an adult weighing 70 kg for therapy and prophylaxis of influenza infections. For human and animal patients of another weight, the daily dose will be proportional to the patient's weight.
In this example, the ratio of terpene to 1,2 dihydroxy propane is as 2.5:100, but other mixture ratios are possible for injections solutions, from 1: 100 to S:100. However, the daily dose of injec~ion solution must then be adapted to the altered terpene content thereof.
xample 2. (Aerosol).
325 g of black-pepper oil are dissolved in 631,8 g of ether mixed with 1805,07 g of ethanol. 31,6 g of esters of castor-oil fatty acids with oxethylated glycerine and 210,6 g of caprylic/capric-acid triglyceride are mixed into this solution. 2.68 g of this mixture, and 2537 g of difluorodichloromethane, are introduced, as a propellant, into a spray-can having a capacity of 20 ccm. The spray-can is closed and comprises a metering valve which releases a predeter~ined amount of the mixture each time it is actuated, in the form of an aerosol, under the pressure from the difluoro-dichloromethane.
A metering valve of the correct size, correctly adjusted, ensures the release, at each actuation, of a single dose containing 6.5 mg of black-pepper oilO
For therapy and prophylaxis in the case of influenza infections, the aerosol is sprayed into the mouth or nose and is inhaledO For a 70 kg .:. , -, .. .
, :................. . . ,:
li~3~65 adult, a suitable daily dose is 8 spray portions, i.e. a total of 8 x 6.5 =
50 mg of black-pepper oil.
Skin areas affected by virus infections may also be treated with the aerosol, in which case seven spray portions each, containing 6.5 mg of black-pepper oil are applied to 50 cm of skin~
In this example, the ratio of terpene to aerosol substance is as 12:100, but other ratios are possible, from 5:100 to 20:100, the daily dose must be adapted to the altered terpene content of each spray portionO
Example 3. (Capsule) A capsule filling is produced from a mixture of 12.5 g of black-pepper oil and 12.5 g of cinnamon-flower oil, with 3 g of soya lecithin as an emulsifier. Each capsule contains 28 mg of this rnixture, the said capsule consisting of 87.5 mg of gelatine and 37.5 mg of glycerine.
For therapy and prophylaxis in the case of influenza infections, one to four of these capsules are administered each day orally to a 70 kg adult. If several capsules are administered, they should be spread over the day.
One capsule contains 25 mg of terpene, but this may be modified to between 10 and 50 g, in which case the daily dose must be adapted to the altered terpene content of the capsules.
Example 4. ~Stick) 1 g of black-pepper oil is mixed with a dimensionally stable carrier compound. ~is compound consists of 59084 g of white vaseline and 39.16 g of paraffin. ~his is mixed thoroughly with the terpene at 70 C, after which it is molded to form a stick and is hardened by coolingO
For local treatment, the stick is applied to the skin in such a manner as to distribute 1 ml of the stick compound - which in this example ' ' ..
- ~ -. . . .:
:
11~316S
contains 5 mg of terpene - over 50 cm of skin. mis may be repeated three times daily.
In this example, the ratio of terpene to carrier compound is as 1:100, but other ratios are possible, for example from 1:100 to 5:100.
Example 5. (Ointment).
3.2 g of hard paraffin and 86.8 g of white vaseline are heated to 60C and stirred togetherO 10 g of cinnamon-flower oil are added to the hot mixture. The mixture is then cooled and may be used as an ointment for local application. hbout 0.1 ml of the ointment - containing about 5 mg of terpene - are spread over 50 cm of skin surface. This may be repeated eight times daily.
The ratio of terpene in the paraffin/vaseline mixture in this example is as 11:100, but other ratios are also possible, for example from 5:100 to 20:100.
Example 6. (Plaster).
A vapour-proof plaster foil is made from a textile fabric by coating the bottom surface with a synthetic material. On the other side - the contact side - the plaster is coated to a depth of 1 mm with a compound made by mixing together 97 g of lead plaster(?)~ 9 g of yellow wax, 9 g of dammar, 10 g of colophonium, and 1 g of turpentineO mis mixture is heated to 100 C and is stirred until the molten mass no longer foams. 5 g of black-pepper oil are then stirred in, after which the compound is applied to the contact side of the plaster foil and is hardened by coolingO
~he contact side of the plaster is applied to the skin and is allowed to remain there for four hours. It may then be replaced with a fresh plaster.
In this example, the ratio of terpene to plaster compo~nd is as 4:100, but other ratios are possible, for example between 1:100 and 10:100~
.. _ _ g _ , .
: , :: . - : :
.. . - : , .. . .
,, ' ' - ' ~ ~ :
~1~316S
The preparation and treatments given in the foregoing examples make it possible to prevent or repress virus attacks, without any cell damage in the organism thus treated or any serious side-effects.
The examples given may be modified by replacing the terpene used with the same amount of another terpene :Erom Table I, or with a mixture of several such terpenes. In all of these cases, virucidal action is achieved without any unwanted side-effects.
The aforementioned micro-organisms are accessible to the public as follows:
1. Girardi Hear~ under CCL27 at ATCC (American Type Culture Collection)
2. Flow 12.000 under 02-150 at Flow Laboratories GmbH (Dietzstr.
lO, 5300 Bonn 3, Fed. Rep. of Germany)
lO, 5300 Bonn 3, Fed. Rep. of Germany)
3. Intestine ~07 under CCL6 at ATCC
4. Vero Kidney under 01-000 at Flow Laboratories GmbH.
'- , '` ~
'- , '` ~
Claims (14)
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:
1. A pharmaceutical preparation for inactivating viruses within living human and animal organisms, comprising one or more spice plant terpenes in admixture with a pharmaceutical-application carrier-substance in a ratio of between 1:100 and 20:100.
2. A pharmaceutical preparation according to claim 1, which com-prises at least one terpene selected from the group consisting of: black-pepper oil, cinnamon-flower oil, cardanum oil, linalyl acetate, cinnamic aldehyde, safrol, carvone and cis/trans citral.
3. A pharmaceutical injection solution according to claim 1 com-prising one or more of the terpenes in admixture with 1,2-dihydroxy propane in a ratio of between 1:100 and 5:100, 2,5:100.
4. A pharmaceutical injection solution according to claim 3 wherein said ratio is 2.5:100.
5. A pharmaceutical aerosol according to claim 1, characterized in that one or more of the terpenes are contained in an aerosol substance in a ratio of between 5:100 and 20:100, and in that the aerosol substance consists of 1 part of ether, 2 to 5 parts of ethanol, 0,02 to 0.1 parts of esters of castor-oil fatty acids with oxethylated glycerine, and 0,2 to 1 parts of caprylic/capric acid triglyceride, pressure being supplied by a propellant gas consisting of 2 to 6 parts of difluoro-dichloro-methane.
6. A pharmaceutical aerosol according to claim 4 wherein said ratio is 12:100.
7. A pharmaceutically administrable capsule according to claim 1, characterized in that a capsule is provided which completely encloses contents of said capsule, said contents consisting of between 10 and 50 mg, of one or more of the terpenes in admixture with 1 to 8 mg of soya lecithin as an emulsifier; said capsule consisting of gelatine and glycerine in a ratio of between 3:1 and 2:1, the total weight of the capsule being between 20 and 200 mg.
8. A pharmaceutically administrable capsule according to claim 7 which includes about 25 mg of said terpene(s).
9. A pharmaceutical stick according to claim 1, characterized in that it consists of a carrier compound which is dimensionally stable but can be applied by rubbing; in that one or more of the terpenes are in admixture with the said carrier compound in a weight ratio of between 1:100 and 5:100, and in that the said carrier compound consists of white vaseline and paraffin in a ratio of between 1:1 and 2:1.
10. A pharmaceutical stick according to claim 9 wherein said weight ratio is about 1:100.
11. A pharmaceutical ointment according to claim 1, characterized in that one or more of the terpenes are in admixture with the ointment carrier-compound in a ratio of between 5:100 and 20:100, and in that the said carrier compound consists of hard paraffin mixed with white vaseline in a ratio of between 1:20 and 1:35.
12. A pharmaceutical ointment according to claim 10 wherein said ratio is about 11:100.
13. A pharmaceutical plaster according to claim 1, characterized by a vapourproof plaster foil coated, on the contact side, to a depth of between 0.5 and 2 mm, with a plaster compound; and in that said plaster compound consists of one or more of said terpenes in admixture with a carrier compound in a ratio of between 1:100 and 10:100, (preferably 4:100); and in that the said carrier compound consists of 90 parts of lead plaster, 7 to 14 parts of yellow wax, 7 to 14 parts of dammar, 8 to 16 parts of colophonium, and 0.5 to 3 parts of turpentine.
14. A pharmaceutical plaster according to claim 13 wherein said ratio is about 4:100.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
LU78955A LU78955A1 (en) | 1978-01-27 | 1978-01-27 | METHOD FOR INACTIVATING VIRUSES |
LU78955 | 1978-01-27 |
Publications (1)
Publication Number | Publication Date |
---|---|
CA1103165A true CA1103165A (en) | 1981-06-16 |
Family
ID=19728832
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA320,356A Expired CA1108463A (en) | 1978-01-27 | 1979-01-26 | Process to obstruct the attack by viruses |
CA320,355A Expired CA1103165A (en) | 1978-01-27 | 1979-01-26 | Process for the inactivation of viruses |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA320,356A Expired CA1108463A (en) | 1978-01-27 | 1979-01-26 | Process to obstruct the attack by viruses |
Country Status (16)
Country | Link |
---|---|
US (3) | US4402950A (en) |
JP (2) | JPS54110310A (en) |
AT (1) | AT374345B (en) |
AU (2) | AU4361779A (en) |
BE (1) | BE873695A (en) |
CA (2) | CA1108463A (en) |
CH (1) | CH640138A5 (en) |
DD (1) | DD143924A5 (en) |
DE (1) | DE2901829A1 (en) |
ES (1) | ES477197A1 (en) |
GB (1) | GB2013086B (en) |
IE (2) | IE47909B1 (en) |
LU (1) | LU78955A1 (en) |
MX (1) | MX5421E (en) |
SE (1) | SE452948B (en) |
ZA (2) | ZA79334B (en) |
Families Citing this family (21)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
LU78955A1 (en) * | 1978-01-27 | 1979-09-06 | Chimicasa Gmbh | METHOD FOR INACTIVATING VIRUSES |
JPS58138460A (en) * | 1982-02-13 | 1983-08-17 | 江崎グリコ栄食株式会社 | Method of keeping fiber products, machine, omstriment or room air sanitary |
IE56078B1 (en) * | 1982-09-30 | 1991-04-10 | Wadley Technologies Inc | Detection of microbial pathogens |
LU85365A1 (en) * | 1984-05-16 | 1986-01-29 | Chimicasa Gmbh | METHOD AND PREPARATION FOR STIMULATING THE IMMUNE SYSTEM |
ES8801173A1 (en) * | 1985-05-25 | 1988-01-01 | Green Cross Corp | Therapeutic and prophylactic agents for peptic ulcer, compounds contained therein and processes for their production. |
US5149715A (en) * | 1989-02-09 | 1992-09-22 | Monterey Mushroom, Inc. | Control of fungal diseases in the production of mushrooms |
JPH02270824A (en) * | 1989-04-13 | 1990-11-05 | Snow Brand Milk Prod Co Ltd | Reverse transcriptase inhibitor |
US5411733A (en) * | 1992-04-27 | 1995-05-02 | Hozumi; Toyoharu | Antiviral agent containing crude drug |
US5839224A (en) * | 1994-12-30 | 1998-11-24 | Proguard, Inc. | Aromatic aldehydes as insecticides and for killing arachnids |
US6251951B1 (en) | 1994-12-30 | 2001-06-26 | Proguard, Inc | Use of flavonoid and aromatic aldehydes as pesticides |
US6750256B1 (en) * | 1994-12-30 | 2004-06-15 | Proguard, Inc. | Use of aromatic aldehydes as insecticides |
US5536501A (en) * | 1994-12-30 | 1996-07-16 | Proguard, Inc. | Use of flavenoid aldehydes as insecticides and for killing arachnids |
US5843375A (en) * | 1995-06-07 | 1998-12-01 | Proguard, Inc. | Method for decontamination of a liquid of gaseous environment |
US5639794A (en) * | 1995-06-07 | 1997-06-17 | Proguard, Inc. | Use of saponin in methods and compositions for pathogen control |
US6632648B1 (en) | 1996-05-14 | 2003-10-14 | Elan Drug Delivery Limited | Methods of terminal sterilization of fibrinogen |
DE19849017C1 (en) * | 1998-10-23 | 2000-03-16 | Dieter Ebert | Dressing for promoting wound healing contains a viscous oily extract of cinnamon leaves |
CA2551454A1 (en) * | 2003-12-24 | 2005-07-07 | Ramot At Tel-Aviv University Ltd. | Antiviral preparations obtained from a natural cinnamon extract |
US20070116852A1 (en) * | 2005-11-22 | 2007-05-24 | Josef Schnatmann | Cattle feed preparation |
ES2392938T3 (en) * | 2010-03-26 | 2012-12-17 | Cesa Alliance S.A. | Antiviral compositions comprising geraniol and carvona |
MA34975B1 (en) * | 2011-03-28 | 2014-03-01 | Cesa Alliance Sa | VIRAL INHIBITOR COMPOSITION FOR IN VIVO THERAPEUTIC USE. |
CN103431198B (en) * | 2013-09-06 | 2014-12-10 | 山东凤祥股份有限公司 | Poultry feed additive and poultry feed |
Family Cites Families (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB455978A (en) * | 1935-04-30 | 1936-10-30 | Hidezo Kimura | Preparation of a remedy for skin diseases and other purposes |
GB508407A (en) * | 1938-03-08 | 1939-06-30 | Thomas Lewis Shepherd | A new and improved disinfectant insecticidal, fungicidal, vermin destroying and therapeutic substance and method of making the same |
GB1060447A (en) * | 1963-05-14 | 1967-03-01 | Maple Leaf Trust | Compositions for the preservation of foodstuffs, for the sterilization and hygiene ofair in confined spaces and for cosmetic and pharmaceutical purposes |
US3595975A (en) * | 1969-07-29 | 1971-07-27 | Holliston Lab Inc | Disinfecting compositions |
FR2062871A1 (en) * | 1969-09-19 | 1971-07-02 | Baranger Pierre | Veterinary antiviral emulsions of terpene alcohols |
DE2309329C2 (en) * | 1973-02-24 | 1983-05-11 | Bayer Ag, 5090 Leverkusen | Use of ethyleneimine solutions as inactivating agents in the manufacture of vaccines |
DE2423073A1 (en) * | 1974-05-13 | 1975-12-11 | Basf Ag | POLYBUTYLENE TEREPHTHALATE MOLDING COMPOUNDS WITH IMPROVED RESISTANCE TO HEAT AND OXYGEN |
LU78955A1 (en) * | 1978-01-27 | 1979-09-06 | Chimicasa Gmbh | METHOD FOR INACTIVATING VIRUSES |
-
1978
- 1978-01-27 LU LU78955A patent/LU78955A1/en unknown
-
1979
- 1979-01-18 DE DE19792901829 patent/DE2901829A1/en active Granted
- 1979-01-18 MX MX797667U patent/MX5421E/en unknown
- 1979-01-24 JP JP623879A patent/JPS54110310A/en active Granted
- 1979-01-24 JP JP623779A patent/JPS54113449A/en active Pending
- 1979-01-24 GB GB7902541A patent/GB2013086B/en not_active Expired
- 1979-01-24 AU AU43617/79A patent/AU4361779A/en not_active Abandoned
- 1979-01-24 AU AU43618/79A patent/AU4361879A/en not_active Abandoned
- 1979-01-24 BE BE6046745A patent/BE873695A/en not_active IP Right Cessation
- 1979-01-25 DD DD79210633A patent/DD143924A5/en unknown
- 1979-01-26 SE SE7900728A patent/SE452948B/en not_active IP Right Cessation
- 1979-01-26 AT AT0060079A patent/AT374345B/en not_active IP Right Cessation
- 1979-01-26 ZA ZA79334A patent/ZA79334B/en unknown
- 1979-01-26 ZA ZA79335A patent/ZA79335B/en unknown
- 1979-01-26 CA CA320,356A patent/CA1108463A/en not_active Expired
- 1979-01-26 CH CH80779A patent/CH640138A5/en not_active IP Right Cessation
- 1979-01-26 CA CA320,355A patent/CA1103165A/en not_active Expired
- 1979-01-26 ES ES477197A patent/ES477197A1/en not_active Expired
- 1979-01-30 IE IE156/79A patent/IE47909B1/en unknown
- 1979-01-30 IE IE155/79A patent/IE47787B1/en unknown
-
1980
- 1980-09-04 US US06/184,135 patent/US4402950A/en not_active Expired - Lifetime
-
1982
- 1982-07-15 US US06/398,705 patent/US4592910A/en not_active Expired - Fee Related
-
1985
- 1985-02-28 US US06/706,470 patent/US4595593A/en not_active Expired - Fee Related
Also Published As
Publication number | Publication date |
---|---|
CA1108463A (en) | 1981-09-08 |
ZA79334B (en) | 1980-02-27 |
IE790155L (en) | 1979-07-27 |
GB2013086A (en) | 1979-08-08 |
JPS54110310A (en) | 1979-08-29 |
DD143924A5 (en) | 1980-09-17 |
CH640138A5 (en) | 1983-12-30 |
US4595593A (en) | 1986-06-17 |
AU4361779A (en) | 1979-08-02 |
ATA60079A (en) | 1983-09-15 |
SE7900728L (en) | 1979-07-28 |
DE2901829A1 (en) | 1979-08-02 |
ZA79335B (en) | 1980-02-27 |
AT374345B (en) | 1984-04-10 |
ES477197A1 (en) | 1979-10-16 |
GB2013086B (en) | 1982-12-22 |
BE873695A (en) | 1979-05-16 |
MX5421E (en) | 1983-08-01 |
LU78955A1 (en) | 1979-09-06 |
IE47787B1 (en) | 1984-06-13 |
DE2901829C2 (en) | 1990-08-09 |
JPH024579B2 (en) | 1990-01-29 |
IE790156L (en) | 1979-07-27 |
US4402950A (en) | 1983-09-06 |
JPS54113449A (en) | 1979-09-05 |
US4592910A (en) | 1986-06-03 |
SE452948B (en) | 1988-01-04 |
AU4361879A (en) | 1979-08-02 |
IE47909B1 (en) | 1984-07-25 |
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