IE920400A1 - Pharmaceutical product for the treatment of virus diseases - Google Patents
Pharmaceutical product for the treatment of virus diseasesInfo
- Publication number
- IE920400A1 IE920400A1 IE040092A IE920400A IE920400A1 IE 920400 A1 IE920400 A1 IE 920400A1 IE 040092 A IE040092 A IE 040092A IE 920400 A IE920400 A IE 920400A IE 920400 A1 IE920400 A1 IE 920400A1
- Authority
- IE
- Ireland
- Prior art keywords
- weight
- product according
- active ingredient
- alcohol
- product
- Prior art date
Links
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title claims abstract description 16
- 201000010099 disease Diseases 0.000 title claims abstract description 13
- 239000000825 pharmaceutical preparation Substances 0.000 title claims description 22
- 229940127557 pharmaceutical product Drugs 0.000 title claims description 21
- 241000700605 Viruses Species 0.000 title claims description 9
- 239000002502 liposome Substances 0.000 claims abstract description 39
- 230000003253 viricidal effect Effects 0.000 claims abstract description 10
- 239000004480 active ingredient Substances 0.000 claims description 37
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 29
- DOUMFZQKYFQNTF-WUTVXBCWSA-N (R)-rosmarinic acid Chemical compound C([C@H](C(=O)O)OC(=O)\C=C\C=1C=C(O)C(O)=CC=1)C1=CC=C(O)C(O)=C1 DOUMFZQKYFQNTF-WUTVXBCWSA-N 0.000 claims description 28
- 150000003904 phospholipids Chemical class 0.000 claims description 26
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 16
- 235000010469 Glycine max Nutrition 0.000 claims description 15
- 244000068988 Glycine max Species 0.000 claims description 15
- DOUMFZQKYFQNTF-MRXNPFEDSA-N rosemarinic acid Natural products C([C@H](C(=O)O)OC(=O)C=CC=1C=C(O)C(O)=CC=1)C1=CC=C(O)C(O)=C1 DOUMFZQKYFQNTF-MRXNPFEDSA-N 0.000 claims description 14
- ZZAFFYPNLYCDEP-HNNXBMFYSA-N Rosmarinsaeure Natural products OC(=O)[C@H](Cc1cccc(O)c1O)OC(=O)C=Cc2ccc(O)c(O)c2 ZZAFFYPNLYCDEP-HNNXBMFYSA-N 0.000 claims description 13
- TVHVQJFBWRLYOD-UHFFFAOYSA-N rosmarinic acid Natural products OC(=O)C(Cc1ccc(O)c(O)c1)OC(=Cc2ccc(O)c(O)c2)C=O TVHVQJFBWRLYOD-UHFFFAOYSA-N 0.000 claims description 13
- 238000000034 method Methods 0.000 claims description 10
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 9
- WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 claims description 9
- 238000002360 preparation method Methods 0.000 claims description 6
- RYCNUMLMNKHWPZ-SNVBAGLBSA-N 1-acetyl-sn-glycero-3-phosphocholine Chemical compound CC(=O)OC[C@@H](O)COP([O-])(=O)OCC[N+](C)(C)C RYCNUMLMNKHWPZ-SNVBAGLBSA-N 0.000 claims description 4
- 239000006185 dispersion Substances 0.000 claims description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims 1
- 230000003612 virological effect Effects 0.000 abstract 2
- 239000013543 active substance Substances 0.000 abstract 1
- 239000000203 mixture Substances 0.000 description 12
- 210000003491 skin Anatomy 0.000 description 11
- 208000009889 Herpes Simplex Diseases 0.000 description 8
- XQFRJNBWHJMXHO-RRKCRQDMSA-N IDUR Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 XQFRJNBWHJMXHO-RRKCRQDMSA-N 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- 150000003839 salts Chemical class 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 206010040880 Skin irritation Diseases 0.000 description 3
- 230000036556 skin irritation Effects 0.000 description 3
- 231100000475 skin irritation Toxicity 0.000 description 3
- PORPENFLTBBHSG-MGBGTMOVSA-N 1,2-dihexadecanoyl-sn-glycerol-3-phosphate Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(O)=O)OC(=O)CCCCCCCCCCCCCCC PORPENFLTBBHSG-MGBGTMOVSA-N 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- 238000005538 encapsulation Methods 0.000 description 2
- 150000002632 lipids Chemical class 0.000 description 2
- 230000002906 microbiologic effect Effects 0.000 description 2
- 239000004570 mortar (masonry) Substances 0.000 description 2
- 150000003905 phosphatidylinositols Chemical class 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 210000000434 stratum corneum Anatomy 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- JZNWSCPGTDBMEW-UHFFFAOYSA-N Glycerophosphorylethanolamin Natural products NCCOP(O)(=O)OCC(O)CO JZNWSCPGTDBMEW-UHFFFAOYSA-N 0.000 description 1
- 208000001688 Herpes Genitalis Diseases 0.000 description 1
- 208000004898 Herpes Labialis Diseases 0.000 description 1
- 208000007514 Herpes zoster Diseases 0.000 description 1
- 206010067152 Oral herpes Diseases 0.000 description 1
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 description 1
- MKUXAQIIEYXACX-UHFFFAOYSA-N aciclovir Chemical compound N1C(N)=NC(=O)C2=C1N(COCCO)C=N2 MKUXAQIIEYXACX-UHFFFAOYSA-N 0.000 description 1
- 229960004150 aciclovir Drugs 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 210000004207 dermis Anatomy 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- -1 for example Substances 0.000 description 1
- 201000004946 genital herpes Diseases 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 210000004379 membrane Anatomy 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000037368 penetrate the skin Effects 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 150000002978 peroxides Chemical class 0.000 description 1
- 150000008104 phosphatidylethanolamines Chemical class 0.000 description 1
- 229960000502 poloxamer Drugs 0.000 description 1
- 229920001983 poloxamer Polymers 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000033764 rhythmic process Effects 0.000 description 1
- 208000017520 skin disease Diseases 0.000 description 1
- OULAJFUGPPVRBK-UHFFFAOYSA-N tetratriacontan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCO OULAJFUGPPVRBK-UHFFFAOYSA-N 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 238000002604 ultrasonography Methods 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
Classifications
-
- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/127—Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Virology (AREA)
- Dispersion Chemistry (AREA)
- Molecular Biology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
A pharmaceutical for treating viral diseases, in particular skin viral diseases, contains at least one virucidal active substance encapsulated in a multilamellar liposome system.
Description
The present invention relates to a pharmaceutical product for the treatment of virus diseases with the characteristics of the general description in claim l.
S in order to treat virus diseases, particularly virus-dependent skin diseases such as, for example, herpes simplex, herpes labialis, herpes genitalis, herpes analis, herpes gest.ationis, herpes facialis, herpes febrilis, herpes menstruelis or herpes zoster, it is customary to apply an ointment-like or cream-like product to the areas of skin affected by the disease. So, for example, the cream fre quently employed for the therapeutic treatment of the aforementioned diseases contains 50 mg acyclovir as active ingredient together with conventional additives such as, for example, propylene glycol, poloxamer and cetylstearyl alcohol.
However, the known creams and ointments suffer from the disadvantage that they must be applied regularly and at short intervals, for example every 2 to 4 hours, since healing or relief cannot otherwise be guaranteed. However, this treatment is not always carried out conscientiously by the patient, so that the desired success frequently does not occur. Furthermore, treatment with the known pharmaceutical products is limited to a few days, for example to 5 or a maximum of 10 days.
The purpose of the present invention is to make available a pharmaceutical product of the aforementioned type that can be applied safely and without side effects over a longer period of time.
According to the invention this purpose is fulfilled by a pharmaceutical product with the characteristic attributes of claim 1.
Thus, according to the invention a pharmaceutical product is proposed for the topical treatment of virus diseases and particularly of virus diseases of the skin, with et least one virucidal active ingredient encapsulated in a multilamellar liposome system.
Whereby in the present application the term liposomes is understood to refer to spheres (vesicles) that are bounded by lipid double membranes and contain within them an aqueous phase in which at least one virucidal active ingredient is dissolved, dispersed or emulsified.
The pharmaceutical product according to the invention exhibits a number of advantages over the known ointment-like or cream-like preparations. Firstly, it has become apparent that, in contrast to the known agents, the preparation
I according to the invention has to be applied to the diseased areas appreciably less frequently over a period of time, for example one day. This is attributed to the pharmaceutical product according to the invention possessing a depot effect since the active ingredient is encapsulated in the liposomes and is slowly and evenly released from these. Furthermore, the therapeutic product according to the invention possesses a better bioavailability, since the liposomes are stored in the skin and particularly in the stratum corneum, so that it is not necessary to cross the barrier of the horny layer. This again leads to the deeper skin layers in the dermis being reached so that the viruses to be found in these deeper skin layers are killed. Furthermore, the pharmaceutical preparation according to the invention possesses a high storage stability, since as stated previously, the minimum of one active ingredient is encapsulated in the liposomes and hence optimally protected against external influences, for example oxidation.
Rosmarinic acid, derivatives and/or salts thereof have been found to be a particularly suitable method of realizing the pharmaceutical product according to the invention. Whereby rosmarinic acid is chemically designated as R{+)-a-[(3-(3,4dihydroxyphenyl)l-oxo-2-propenyl]oxy] -3,4-dihydroxybenzene propionic acid and is represented by the following structural formula:
HO •OH
MO
OH
The derivatives of rosmarinic acid that come into question are particularly the esters, preferably the methyl, ethyl, propyl, butyl esters, whereby esterification can involve both the COOH group and the aromatic hydroxy groups. In. the case of the salts, the alkali metal and alkaline earth salts in particular are preferred.
The concentration of the virucidal active ingredient or of the mixture of virucidal active ingredients in the pharma10 ceutical product according to the invention is adjusted according to the nature of the virucidal compounds employed, the regions of the body to be treated and the severity of the disease. In general the concentration of virucidal active ingredient in the product according to the invention ranges from 0.001* by weight to 5* by weight of the mass of the liposome system in which the active ingredient is encapsulated. In the case of mild disorders and for application to the mucosa application forms of the product according to the invention are employed whose active ingredient concen20 tration lies between 0.001* by weight and 0.1* by weight. In the case of severe disorders and particularly of those disorders where the virus infection does not extend to the mucous membranes, products are preferably used whose active ingredient concentration lies between 0.1* by weight and 2* by weight. However, if it is desired to exploit the depot effect brought about by encapsulation of the active ingredient or active Ingredient mixture in the liposome system the active ingredient concentration in the product according to the invention can be raised to 2* by weight to 5* by weight, whereby such a product must be applied at correspondingly extended intervals, particularly in a 24 hour rhythm. The aforementioned concentration ranges are in each case with respect to the mass of the liposome system that encapsulates the active ingredient or the active ingredient mixture .
In order to improve the deposition of the product in the skin and particularly in the stratum corneum in the case of the product according to the invention such liposome systems are preferably chosen whose liposomes have a mean diameter between 100 nm and 500 nm. Here liposome systems with a mean liposome diameter of about 150 nm to about 300 nm have shown themselves to be particularly advantageous.
It has also been established to be advantageous, that such liposome systems that exhibit a negative surface charge penetrate the skin particularly rapidly and well and, hence, possess high effectivity.
With respect to the liposome system encapsulating the active ingredient or mixture of active ingredients in the pharmaceutical product according to the invention, it may be stated in general that any suitable liposome system may be used that fulfils the aforementioned conditions concerning mean diameter and surface charge and forms multilamellar vesicles. However, the product according to the invention is preferably used in which the liposomes are present in the form of a gel-like dispersion, that contains 8 to 22¾ by weight soya phospholipids together with water and/or alcohol in addition to the active ingredient or active ingredient mixture.
A particularly high efficacy, expressed in the form of a good depot effect, and a particularly good bioavailability of the active ingredient or of the active ingredient mixture are exhibited by forms of realization of the pharmaceutical product according to the invention where the soya phospholipids contain a high concentration of phosphatidylcholine, particularly from 60¾ by weight to 98¾ by weight phosphatidylcholine and 2¾ to 40¾ by weight of other phospholipids, such as, in particular, phosphatidylethanolamine, phosphatidic acid and/or phosphatidylinositol.
A further improvement in efficacy, particularly with respect to herpes simplex, is achieved for the product according to the invention where a liposome system is used which is made up of specific soya phospholipids, whereby these specific soya phospholipids contain 76 ± 3% by weight phosphatidylcholine and 0 to 6¾ by weight lysophosphatldylcholine. Moreover, these soya phospholipids can also contain the aforementioned other phospholipids particularly ca. 5* by weight phosphatidylethanolamlne, ca. 8* by weight phosphatidic acid and/or traces of phosphatidylinositol. In particular such a liposome system is excellently suitable for the encapsulation of active ingredients based on rosmarinic acid, rosmarinic acid derivatives and/or salts of rosmarinic acid, and for the release of these evenly over an appropriately extended period of time after penetration into the skin of the liposomes so loaded, so that such a mode of execution of the product according to the invention possesses an excellent depot effect and, hence, an excellent long-term effect.
A form of realization of the product according to the invention characterized by high purity soya phospholipids containing 93 ± 3* by weight phosphatidylcholine and 0-6% by weight lysophosphatidylcholine was found to be particularly suitable for the complete avoidance of undesired but harmless side effects, such as, for example, the occurrence of skin reddening in especially sensitive patients, and for further improvement of the aforementioned advantages. These soya phospholipids do not contain or contain only traces of the aforementioned other phospholipids whose detection limit is ca. 0.5% by weight.
In order to ensure that the product according to the invention has a long storage life and in particular to ensure good liposome stability, the product according to the invention contains, in addition to the liposome system and the active ingredient, between ca. 12* by weight and ca. 20* by weight, preferably ca. 16* by weight alcohol, particularly ethanol and/or 2-propanol as well as between ca. 80* by weight and about 58* by weight water. In this context it has been established that in addition to exhibiting excellent storage properties over several years such a product ls also topically applicable with outstanding effectivlty and with10 out the occurrence of skin irritation.
The present invention also refers to a method for the preparation of the aforementioned pharmaceutical product containing soya phospholipids of the aforementioned type as the liposome system.
According to the invention such a product is prepared by dissolving a phospholipid mixture In alcohol, preferably ethanol and/or 2-propanol, and thereafter adding sufficient water to produce a gel and then mixing the gel, for example by stirring, with at least one active ingredient.
Unexpectedly it could be established that the aforementioned method resulted in the formation of liposomes, that encapsu25 late the aforementioned added active ingredient, whereby these liposomes display a defined and constant particle size between ca. 150 nm and ca. 300 nm, preferably ca. 230 nm. Furthermore, it could also be established that, as a result of the addition of water and/or further dilution with water, free liposomes with several bilayers were formed in the pharmaceutical product. Furthermore, in the method according to the invention it is not necessary to carry out additional, energy-consuming steps involving, for example, the raising of the temperature, the application of ultrasound or excessive stirring in order to prepare the liposomes and encapsulate the active ingredient or mixture of active ingredients. It is sufficient here if the above-mentioned components are stirred together for 2 to 8 minutes with a laboratory stirrer of conventional construction. Further5 more, it was also possible to establish that the product according to the invention has an extremely low microbiological count of less than 100 organisms/g, thus fulfilling the USP 21 and DAB 9 standards.
A further mode of execution of the method according to the invention proposes that the phospholipid mixture be dissolved in only a part of the reguired quantity of alcohol and that the remaining part of the alcohol be added during and/or after stirring the gel with the active ingredient and then the necessary amount of water be added in order to adjust the viscosity to that desired for the pharmaceutical product. Here it has been found to be particularly suitable when the phospholipid mixture is first dissolved in 10¾ by weight to 30¾ by weight of the required amount of alcohol and then the remaining alcohol, i.e. 70¾ by weight to 90¾ by weight, is added during and/or after stirring the gel with the active ingredient.
Advantageous developments of the pharmaceutical product according to the invention are mentioned in later claims.
The pharmaceutical product according to the invention will be further explained with the aid of two execution examples.
Example 1 g of a phospholipid mixture comprising
82.5 ± 3.5¾ by weight phosphatidylcholine (3-Si-PC), not more than 10¾ by weight phosphatldylethanolamlne
- 6* by weight lyeophosphatidylcholine and t more than 10* by weight other lipids with a peroxide value of not more than 5 and a total microbiological count of not more than 100 organisms/g was dissolved in 3.6 g ethanol. Then 47 g demineralized water was added to this solution and the solution was homogenized for 3 minutes with a rapidly operating laboratory stirrer. A transparent gel was produced thereby. This gel was stirred with 12.4 g ethanol and 1.01 g rosmarinic acid (rapidly operating laboratory stirrer, 2 minutes). Then the batch was made up to 100 g finished product by the addition of demineralized water followed by a final stirring with a rapidly operating laboratory stirrer for 2 minutes.
The product so produced was designated product 1.
A product 2 was prepared in parallel, whereby the same starting materials were used in identical amounts as for product 1. However, this time the 1.01 g rosmarinic acid was not added until the last water had been added and the rosmarinic acid and the liposome system were mixed manually in a conventional mortar.
A product 3 was also prepared in parallel, whereby product 3 contained the same components as product 1 except that rosmarinic acid was omitted from product 3.
The aformentioned products 1 to 3 were tested on a group of 30 randomly chosen patients all suffering from herpes sim30 plex. For this purpose products 1 to 3 were applied locally to the diseased areas of skin and briefly rubbed In twice daily at 12 hourly intervals.
Only three days after the beginning of the treatment there was an appreciable improvement in the disease in patients treated with product 1 and 2. After 6 days of application of product 1 and 2 60* of the patients treated no longer exhibited herpes simplex. The remaining 40* of the patients no longer exhibited any herpes simplex after a further 4 days of treatment.
All patients treated with product 3 exhibited unchanged herpes simplex even after treatment for a period of 10 days.
Example 2 g of a phospholipid mixture (soya phospholipid), comprising
95* by weight phosphatidylcholine,
3% by weight lysophosphatidylcholine and
2* by weight other not identified phospholipids was dissolved in 3.6 g ethanol. Then 47 g demineralized water was added to this solution and the solution was homo20 genized for three minutes with a rapidly operating laboratory stirrer. A transparent gel was produced thereby. This gel was stirred with 12.4 g ethanol and 1.01 g rosmarinic acid (rapidly operating laboratory stirrer, 2 minutes). Then the batch was made up to 100 g finished product by the addition of demineralized water followed by a final stirring with a rapidly operating laboratory stirrer for 2 minutes.
The product so produced was designated product 4.
A product 5 was also prepared in parallel, whereby the same starting materials were used in identical amounts as for product 4. However this time the 1.01 g rosmarinic acid was not added until the last water had been added and the rosmarinic acid and the liposome system were mixed manually in a conventional mortar.
A product 6 was also prepared in parallel, whereby product 6 contained the same components as product 4 except that rosmarinic acid was omitted from product 6.
The aforementioned products 4 to 6 were tested on a group of 30 specifically chosen patients all suffering from herpes simplex who all complained of skin irritation after the application of other preparations. For this purpose products 4 to 6 were applied locally to the diseased areas of skin and to the neighbouring healthy areas of skin and briefly rubbed in twice daily at 12 hourly intervals.
With respect to the treatment of herpes simplex the results were basically the same as those obtained in example 1, whereby the impression was obtained that the total treatment times tended to be shortened by about 1 to 2 days. However, it was worthy of note that none of the patients suffered skin irritation.
This treatment investigation was naturally also confirmed by the fact that all the patients treated with product 6 exhibited unchanged herpes simplex even after treatment for a period of 14 days.
Claims (17)
1. Pharmaceutical product for the treatment of virus diseases, particularly virus diseases of the skin, with at least one virucidal active ingredient, wherein the active ingredient is encapsulated in a multilamellar liposome 5 system.
2. Product according to claim 1, wherein it contains rosmar inic acid, rosmarinic acid-derivatives and/or -salts thereof as virucidal active ingredient.
3. Product according to claim 1 or 2, wherein it contains the virucidal active ingredient in a concentration between 0.001¾ by weight and 5¾ by weight relative to the mass of the liposome system. is
4. Product according to the aforementioned claims, wherein it contains a liposome system, containing liposomes with a mean diameter of between 100 nm and 500 nm
5. Product according to claim 4, wherein the liposomes of the liposome system possess a mean diameter of between about 150 nm and 300 nm. 5
6. Product according to one of the aforementioned claims, wherein it contains a liposome system that possesses a negative surface charge.
7. Product according to one of the aforementioned claims, 10 wherein the liposome system is a gel-like liposome dispersion, that contains, in addition to at least one active ingredient,
8. To 22% by weight soya phospholipids as well as water and/or alcohol. 15 8. Product according to claim 7, wherein the soya phospholipids contain 60 to 98% by weight phosphatidylcholine and 2 to 40% by weight other phospholipids.
9. Product according to claim 7 or 8, wherein the soya phospholipids contain 76 ± 3% by weight phosphatidylcholine and 25 0 to 6% by weight lysophosphatidylcholine.
10. Product according to claim 8 or 9, wherein the soya phospholipids contain 30 93 ± 3% by weight phosphatidylcholine and 0 to 6% by weight lysophosphatidylcholine.
11. Product according to one of claims 5 to 10, wherein the liposome system contains between 12* by weight and 20* by weight alcohol, in particular ethanol and/or 2-propanol, and between 80* by weight and 58* by weight water in addition to 5 the phospholipids.
12. Method of preparation of the pharmaceutical product according to one of claims 7 to 11, wherein the soya phospholipids are dissolved in alcohol, preferably ethanol or 210 propanol, then sufficient water is added to produce a gel and the gel is mixed with at least one active ingredient.
13. Method according to claim 12, wherein the soya phospholipids are dissolved in only a portion of the quantity of 15 alcohol and the remainder of the alcohol and water is added during and/or after mixing the gel with the active ingredient.
14. Method according to claim 13, wherein the first portion 20 of the alcohol amounts to between 10 and 30* by weight and the remaining portion lies between 70 and 90* by weight.
15. A method of preparation of a pharmaceutical product according to any of claims 1 to 11 substantially as hereinbefore described by way of Example.
16. A pharmaceutical product whenever prepared by a method as claimed in any of claims 12 to 15.
17. A pharmaceutical product substantially as hereinbefore described by way of Example.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE4103732 | 1991-02-07 | ||
| DE4121389A DE4121389A1 (en) | 1991-02-07 | 1991-06-28 | PHARMACEUTICAL PRODUCT FOR TREATING VIRUS DISEASES |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| IE920400A1 true IE920400A1 (en) | 1992-08-12 |
Family
ID=25900838
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IE040092A IE920400A1 (en) | 1991-02-07 | 1992-02-06 | Pharmaceutical product for the treatment of virus diseases |
Country Status (6)
| Country | Link |
|---|---|
| EP (1) | EP0527979A1 (en) |
| JP (1) | JPH05506671A (en) |
| CA (1) | CA2079868A1 (en) |
| DE (1) | DE4121389A1 (en) |
| IE (1) | IE920400A1 (en) |
| WO (1) | WO1992013524A1 (en) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE9312509U1 (en) * | 1993-08-20 | 1993-10-28 | Euro-Celtique S.A., Luxemburg/Luxembourg | Preparations for external administration of antiseptic and / or wound healing promoting agents |
| EP0704206B1 (en) * | 1994-09-30 | 2002-09-04 | MIKA Pharma Gesellschaft für die Entwicklung und Vermarktung pharmazeutischer Produkte mbH | Pharmaceutical composition |
| IE960485A1 (en) * | 1996-07-02 | 1998-01-14 | Univ Dublin | Organised assemblies containing entrapped negatively charged¹polyelectrolytes |
| WO1998017284A2 (en) * | 1996-10-22 | 1998-04-30 | Daniel Favre | Inhibition of cap-independent protein synthesis and hiv-tar translation by heparin or heparin mimetics, and methods for gene therapy |
| US20030181416A1 (en) * | 2002-01-10 | 2003-09-25 | Comper Wayne D. | Antimicrobial charged polymers that exhibit resistance to lysosomal degradation during kidney filtration and renal passage, compositions and method of use thereof |
| ES2526264B1 (en) * | 2013-06-05 | 2015-12-02 | Consejo Superior De Investigaciones Cientificas (Csic) | SEQUENCE OF NUCLEOTID CODING OF AN ENZYME WITH DEXTRANSACARASA ACTIVITY, CELLS THAT EXPRESS IT AND ITS USE FOR THE OBTAINING OF EXOPOLISACARIDS WITH ANTIVIRAL ACTIVITY AND COMPOSITIONS CONTAINING THEM |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0066379A3 (en) * | 1981-05-15 | 1983-06-08 | Riker Laboratories, Inc. | Composition for combating herpes virus |
| EP0172007B1 (en) * | 1984-08-10 | 1991-05-22 | Syntex (U.S.A.) Inc. | Stable liposomes with aqueous-soluble medicaments and methods for their preparation |
| WO1991001719A1 (en) * | 1989-08-01 | 1991-02-21 | The University Of Michigan | Topical delivery of peptides/proteins entrapped in dehydration/rehydration liposomes |
-
1991
- 1991-06-28 DE DE4121389A patent/DE4121389A1/en not_active Withdrawn
-
1992
- 1992-02-03 WO PCT/DE1992/000078 patent/WO1992013524A1/en not_active Ceased
- 1992-02-03 JP JP92503906A patent/JPH05506671A/en active Pending
- 1992-02-03 CA CA002079868A patent/CA2079868A1/en not_active Abandoned
- 1992-02-03 EP EP19920904330 patent/EP0527979A1/en not_active Withdrawn
- 1992-02-06 IE IE040092A patent/IE920400A1/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| EP0527979A1 (en) | 1993-02-24 |
| CA2079868A1 (en) | 1992-08-08 |
| DE4121389A1 (en) | 1992-08-13 |
| WO1992013524A1 (en) | 1992-08-20 |
| JPH05506671A (en) | 1993-09-30 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU758188B2 (en) | Improved personal care formulations | |
| US4610978A (en) | Compositions containing 1α-hydroxycholecalciferol for topical treatment of skin disorders and methods employing same | |
| DE69735949T2 (en) | COMPOSITION SUITABLE FOR THE TREATMENT OF HORSE MILF | |
| US5851543A (en) | Skin care preparation and method | |
| CN100396287C (en) | Formulations containing phosphate derivatives of electron transfer agents | |
| JPH0148885B2 (en) | ||
| US20080254084A1 (en) | Antimicrobial Preparations Having a Content of Octenidine Dihydrochloride Encapsulated in Liposomes | |
| USRE33107E (en) | Compositions containing 1α-hydroxycholecalciferol for topical treatment of skin disorders and methods employing same | |
| EP2234582A2 (en) | Improving the appearance of nails | |
| JPH11302155A (en) | Skin external preparation for atopic dermatitis | |
| JPH0761940B2 (en) | Liposomal formulation for outer skin | |
| IE920400A1 (en) | Pharmaceutical product for the treatment of virus diseases | |
| US4518583A (en) | Hemorrhoid and anorectal disease treatment method | |
| IE920401A1 (en) | Pharmaceutical product for the treatment of virus diseases | |
| DE69206913T2 (en) | Formulations for the treatment of vaginal dryness | |
| US5128375A (en) | Keloid treating agent | |
| US6469070B1 (en) | Topical medicament comprising phenolic biocide and choline | |
| CN1292751C (en) | Imiquimod or its derivative liposome for local skin and its preparing method and use | |
| US20060154983A1 (en) | Use of a composition comprising vitamin k1 oxide or a derivative thereof for the treatment and/or the prevention of mammal dermatological lesions | |
| RU2560698C1 (en) | Topical agent for acne | |
| CARRUTHERS | DERMATOLOGICAL TREATMENT | |
| CZ115699A3 (en) | Cosmetic composition |