GB2398495A - A drug delivery preparation comprising at least one anti-tumour drug and a topical carrier for the drug - Google Patents
A drug delivery preparation comprising at least one anti-tumour drug and a topical carrier for the drug Download PDFInfo
- Publication number
- GB2398495A GB2398495A GB0301562A GB0301562A GB2398495A GB 2398495 A GB2398495 A GB 2398495A GB 0301562 A GB0301562 A GB 0301562A GB 0301562 A GB0301562 A GB 0301562A GB 2398495 A GB2398495 A GB 2398495A
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- United Kingdom
- Prior art keywords
- drug
- delivery preparation
- drug delivery
- preparation according
- bleomycin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/14—Peptides containing saccharide radicals; Derivatives thereof, e.g. bleomycin, phleomycin, muramylpeptides or vancomycin
-
- 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—Liposomes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Epidemiology (AREA)
- Dispersion Chemistry (AREA)
- Gastroenterology & Hepatology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (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)
Abstract
A drug delivery preparation comprising at least one anti-tumour drug and a topical carrier for the drug, the carrier comprising a lipid and a surfactant, the lipid being such that it is able to entrap the drug, the drug being a drug that has difficulty in penetrating a patient's skin in effective amounts, and the surfactant being such that it confers elastic properties to the drug delivery preparation whereby the lipid and the surfactant promote the passage of the drug into the patient's skin. Preferably, the carrier is an elastic liposome and surfactant is a cholate. More preferably, the anti-tumour drug is bacteria derived, preferably bleomycin A2 or bleomycin B2.
Description
A DRUG DELIVERY PREPARATION COMPRISING
AT LEAST ONE ANTI-TUMOUR DRUG AND
-
A TOPICAL CARRIER FOR THE DRUG
This invention relates to a topical drug delivery preparation and, more specifically, this invention relates to a topical drug delivery preparation comprising at least one anti-tumour drug and a topical carrier for the drug.
Topically used drugs are used in the treatment of various skin problems including skin cancer. Often the drugs have difficulty in penetrating a patient's skin in effective amounts. Topical carriers enable the drugs to penetrate the patient's skin in effective amounts. Vesicles were postulated as possible carriers by Mezei and Gulasekharam in 1980 (Mezei, M. and Gulasekharam, V. [1980] Liposomes: a selective drug delivery system for the topical route of administration. Life Sciences 26: 1473- 1477).
The vesicles are hollow, usually spherical, particles formed from the association of one or more layers of material. In 1997, Cevc et al proposed the use of ultra-deformable vesicles (Cevc, G., Blume, G. and Schatzlein, A. [1997] Transfersome-mediated transepidermal delivery improves the regio- specificity and biological activity of corticosteroids in viva. Joumal of Controlled Release 45(3J: 211-226). In 1999 and 2001, van den Bergh et al proposed the use of elastic vesicles for the purpose of penetrating pathways in the skin through which drugs molecules could diffuse (van den Bergh, B.A.I., Vroom, J. Gemtsen, H., Junginger, H.E. and Bouwstra, J.A. [1999] Interactions of elastic and rigid vesicles with human skin in vitro: electron microscopy and two-photon excitation microscopy. Biochimica et Biophysica Acta 1461: 155-173; van den Bergh, B.A.I., Wertz, P.W., Junginger, H.E., and Bouwstra, J.A. [2001] Elasticity of vesicles assessed by electron spin resonance, electron microscopy and extrusion measurements. Intemational Joumal of Pharmaceutics 217: 13-24).
It is an aim of the present invention to provide a novel topical drug delivery preparation comprising at least one anti-tumour drug.
Accordingly, in one non-limiting embodiment of the present invention there is provided a drug delivery preparation comprising at least one antitumour drug and a topical carrier for the drug, the carrier comprising a lipid and a surfactant, the lipid being such that it is able to entrap the drug, the drug being a drug that has difficulty in penetrating a patient's skin in effective amounts, and the surfactant being such that it confers elastic properties to the drug delivery preparation whereby the lipid and the surfactant promote the passage of the drug into the patient's skin.
The drug delivery preparation of the present invention is able to be used for facilitating the use of anti-tumour drugs in effective amounts and in a more efficient manner than has hitherto been achievable. The patient will usually be a human patient but it may be an animal patient in some cases.
Preferably, the carrier is an elastic liposome. Other types of carriers may be, for example, lipid emulsions or lipid nanoparticles.
The topical carrier may be one in which the lipid is present in a concentration of 0.001 mg/ml to 10 g/ml.
Preferably, the surfactant is a cholate. Other types surfactants that may be employed are, for example, Tween 80 or Triton-X (Registered Trade Marks). The Triton-X is produced from octylphenol polymerised with ethylene oxide. The Tween 80 is a polyoxyethylene sorbitan monooleate.
The topical carrier may include an excipient. Any suitable and appropriate type of excipient may be employed. Thus, for example, the excipient may be a preservative, or more generally, an excipient which has a beneficial effect on the stability and controlled release of the drug from the topical carrier.
The topical carrier may be used in any suitable and appropriate form such for example as in the form of a cream, ointment, gel or liquid.
The drug may be a water-soluble and/or a lipid-soluble drug. The drug may be a bacteria-derived anti-tumour drug. The drug may be used for treating malignant skin cancers, vulvar intraepithelial neoplasia, vulval squamous cell carcinoma, actinic keratoses, keratoacanthomas, kaposi sarcoma, Bowen's disease, and all benign tumours of viral aetiology such for example as Human papilloma virus, Herpes Simplex virus type 8, and Molluscum contagiosum.
Preferably, the drug is bleomycin. The bleomycin may be active bleomycin A2 and B2. Alternatively, the bleomycin may be active bleomycin A2. Alternatively, the bleomycin may be active bleomycin B2.
An embodiment of the invention will now be described solely by way of example and with reference to the accompanying drawings and the
following Example.
In the accompanying drawings: Figure 1 is a cross sectional diagrammatic representation of human skin; Figure 2 is a pictorial representation of a drug delivery preparation according to the present invention being used on the human skin; Figure 3 is a pictorial explanation of the function of the lipid used in the topical carrier of the present invention; and Figure 4 gives the general formula of bleomycin sulphate, and active bleomycin A2 sulphate in particular.
Referring to Figure 1, there is shown a section through the skin 2 of a human patient. As can be seen, the skin 2 comprises epidermis 4, dermis 6 and a fat layer 8. The epidermis 4 and the dermis 6 may be 2-4 mm thick.
Also shown in Figure 1 are a hair 10, melanocytes 12, a nerve 14, a sweat gland 16, and blood vessels 18.
Figure 2 is a pictorial representation of a lipid-based drug delivery preparation, loaded with active anti-tumour drug(s), penetrating and releasing the drug(s) into the human skin 2.
Figure 3 is a pictorial representation of the encapsulation action of water-soluble drugs such as bleomycin, and lipid-soluble drugs in an elastic carrier such for example as an elastic liposome. As can be seen from Figure 3, lipids are the building blocks of membranes. Liposomes are generated when lipid molecules are dispersed in water. The liposomes can entrap drugs inside, for subsequent delivery to a particular site in the skin. s
Figure 3 shows lipid-soluble drugs entrapped in a membrane, and also water-soluble drugs entrapped by the liposomes.
Figure 4 shows the chemical structure for active bleomycin A2, where xH2SO4 represents the sulphate salt of the drug.
EXAMPLE I
Soya or egg-derived phosphatidylcholine (ePC) was obtained from Avanti Lipids (USA). Sodium Cholate was obtained from Wako Chemicals (Japan). All solvents, chemicals and reagents were of analytical grade.
Bleomycin sulphate for injection was obtained from Nippon Kayaku (Japan), and the main components by weight were active bleomycin A2 (68.6%), active bleomycin B2 (30.6%), and inactive bleomycin A2 (0.8%), as determined by the supplier.
The lipid-cholate mixture was dissolved in 5 ml ethanol and the solvent was removed by rotary evaporation, under a nitrogen gas atmosphere, to leave a dry-film lipid residue. This film was hydrated with 1 ml of bleomycin sulphate, 10 mg/ml, and transformed into multi-lamellar vesicles by vortexing with glass beads and brief bath-sonication. This iiposomal bleomycin suspension was diluted with 9 ml of milli-Q distilled water.
The produced drug delivery preparation was used to treat a 78-year- old former labourer who had multiple basal cell carcinomas on the temples and forehead. The drug delivery preparation was in the form of a cream which was applied twice a day for four weeks. At Relend of the treatment, the multiple basal cell carcinomas on the temples and forehead had disappeared.
The cream produced in accordance with Example I may be used to treat all malignant skin cancers, vulvar intraepithelial neoplasia, vulval squamous cell carcinoma, actinic keratoses, keratoacanthomas, kaposi sarcoma, Bowen's disease, and all benign turnouts of viral aetiology such for example as Human papilloma virus, Herpes Simplex virus type 8, or Molluscum contagiosum.
In alternative embodiments of the invention, the lipid may be in the form of an emulsion or in the form of nanoparticles rather than being in the form of a liposome.
Claims (15)
1. A drug delivery preparation comprising at least one anti-tumour drug and a topical carrier for the drug, the carrier comprising a lipid and a surfactant, the lipid being such that it is able to entrap the drug, the drug being a drug that has difficulty in penetrating a patient's skin in effective amounts, and the surfactant being such that it confers elastic properties to the drug delivery preparation whereby the lipid and the surfactant promote the passage of the drug into the patient's skin.
2. A drug delivery preparation according to claim 1 in which the carrier is an elastic liposome.
3. A drug delivery preparation according to claim 1 or claim 2 in which the lipid is present in a concentration of 0.001 mg/ml to 10 g/ml.
4. A drug delivery preparation according to any one of the preceding claims in which the surfactant is a cholate.
5. A drug delivery preparation according to any one of the preceding claims and including an excipient.
6. A drug delivery preparation according to claim 5 in which the excipient is a preservative.
7. A drug delivery preparation according to any one of the preceding claims and in the form of a cream, ointment, gel or liquid.
8. A drug delivery preparation according to any one of the preceding claims in which the drug is a water-soluble and/or a lipid-soluble drug.
9. A drug delivery preparation according to claim 8 in which the drug is a bacteria-derived anti-tumour drug.
10. A drug delivery preparation according to any one of the preceding claims in which the drug is a drug for treating malignant skin cancers, vulvar intraepithelial neoplasia, vulval squamous cell carcinoma, actinic keratoses, keratoacanthomas, kaposi sarcoma, Bowen's disease, and all benign tumours of viral aetiology.
11. A drug delivery preparation according to any one of the preceding claims in which the drug bleomycin.
12. A drug delivery preparation according to claim 11 in which the bleomycin is active bleomycin A2 and B2.
13. A drug delivery preparation according to claim 11 in which the bleomycin is active bleomycin A2.
14. A drug delivery preparation according to claim 11 in which the bleomycin is active bleomycin B2.
15. A drug delivery preparation according to claim 1 and substantially as herein described.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB0301562A GB2398495B (en) | 2003-01-23 | 2003-01-23 | A drug delivery preparation comprising at least one anti-tumour drug and a topical carrier for the drug |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB0301562A GB2398495B (en) | 2003-01-23 | 2003-01-23 | A drug delivery preparation comprising at least one anti-tumour drug and a topical carrier for the drug |
Publications (3)
Publication Number | Publication Date |
---|---|
GB0301562D0 GB0301562D0 (en) | 2003-02-26 |
GB2398495A true GB2398495A (en) | 2004-08-25 |
GB2398495B GB2398495B (en) | 2007-08-22 |
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Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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GB0301562A Expired - Lifetime GB2398495B (en) | 2003-01-23 | 2003-01-23 | A drug delivery preparation comprising at least one anti-tumour drug and a topical carrier for the drug |
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GB (1) | GB2398495B (en) |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2006083979A2 (en) * | 2005-02-02 | 2006-08-10 | Nexgenix Pharmaceuticals, L.L.C. | Local treatment of neurofibromas |
WO2008065369A2 (en) * | 2006-11-28 | 2008-06-05 | Sunil Chopra | A bleomycin preparation for use against skin tumours |
US20090111784A1 (en) * | 2006-05-12 | 2009-04-30 | Alexander Tobias Teichmann | Medication against breast cancer and related diseases |
GB2595502A (en) * | 2020-05-28 | 2021-12-01 | Chopra Sunil | Compounds, compositions and methods for the treatment or prevention of hair loss |
Citations (6)
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---|---|---|---|---|
US4156719A (en) * | 1977-02-28 | 1979-05-29 | Yamanouchi Pharmaceutical Co., Ltd. | Compositions for rectal use |
EP0219922A2 (en) * | 1985-10-15 | 1987-04-29 | Vestar, Inc. | Anthracycline antineoplastic agents encapsulated in phospholipid micellular particles |
JPH0374334A (en) * | 1989-08-11 | 1991-03-28 | Nippon Oil & Fats Co Ltd | Reinforcing of carcinostatic property of bleomycin |
EP0526666A1 (en) * | 1991-08-05 | 1993-02-10 | Maria Rosa Gasco | Solid lipid microspheres having a narrow size distribution and method for producing them |
GB2315216A (en) * | 1993-10-05 | 1998-01-28 | Ciba Geigy Ag | Microemulsion preconcentrates comprising FK 506 |
GB2327610A (en) * | 1994-11-04 | 1999-02-03 | Novartis Ag | Stabilisation of Macrolide Compositions |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR100464601B1 (en) * | 1998-10-23 | 2004-12-31 | 이데아 악티엔게젤샤프트 | Method for developing, testing and using associates of macromolecules and complex aggregates for improved payload and controllable de/association rates |
WO2001001962A1 (en) * | 1999-07-05 | 2001-01-11 | Idea Ag. | A method for the improvement of transport across adaptable semi-permeable barriers |
-
2003
- 2003-01-23 GB GB0301562A patent/GB2398495B/en not_active Expired - Lifetime
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4156719A (en) * | 1977-02-28 | 1979-05-29 | Yamanouchi Pharmaceutical Co., Ltd. | Compositions for rectal use |
EP0219922A2 (en) * | 1985-10-15 | 1987-04-29 | Vestar, Inc. | Anthracycline antineoplastic agents encapsulated in phospholipid micellular particles |
JPH0374334A (en) * | 1989-08-11 | 1991-03-28 | Nippon Oil & Fats Co Ltd | Reinforcing of carcinostatic property of bleomycin |
EP0526666A1 (en) * | 1991-08-05 | 1993-02-10 | Maria Rosa Gasco | Solid lipid microspheres having a narrow size distribution and method for producing them |
GB2315216A (en) * | 1993-10-05 | 1998-01-28 | Ciba Geigy Ag | Microemulsion preconcentrates comprising FK 506 |
GB2327610A (en) * | 1994-11-04 | 1999-02-03 | Novartis Ag | Stabilisation of Macrolide Compositions |
Non-Patent Citations (1)
Title |
---|
WPI Acc. No. 1991-136900 [25] & JP 3074334 A (NIPPON OILS & FATS) * |
Cited By (18)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2013136617A (en) * | 2005-02-02 | 2013-07-11 | Nexgenix Pharmaceuticals Llc | Local treatment of neurofibroma |
WO2006083979A3 (en) * | 2005-02-02 | 2006-10-19 | Nexgenix Pharmaceuticals L L C | Local treatment of neurofibromas |
WO2006083979A2 (en) * | 2005-02-02 | 2006-08-10 | Nexgenix Pharmaceuticals, L.L.C. | Local treatment of neurofibromas |
JP2008528692A (en) * | 2005-02-02 | 2008-07-31 | ネクスジェニクス・ファーマシューティカルズ,リミテッド・ライアビリティ・カンパニー | Local treatment of neurofibroma |
CN101155577B (en) * | 2005-02-02 | 2015-04-22 | 耐克斯詹尼克斯医药有限公司 | Local treatment of neurofibromas |
US8487004B2 (en) | 2005-02-02 | 2013-07-16 | Nexgenix Pharmaceuticals, Inc. | Local treatment of neurofibromas |
AU2006210787B2 (en) * | 2005-02-02 | 2012-05-24 | Nexgenix Pharmaceuticals, L.L.C. | Local treatment of neurofibromas |
US8211875B2 (en) | 2005-02-02 | 2012-07-03 | Nexgenix Pharmaceuticals Inc | Local treatment of neurofibromas |
AU2006210787C1 (en) * | 2005-02-02 | 2013-01-17 | Nexgenix Pharmaceuticals, L.L.C. | Local treatment of neurofibromas |
US9114163B2 (en) * | 2006-05-12 | 2015-08-25 | Mabel Gmbh | Medication against breast cancer and related diseases |
US20090111784A1 (en) * | 2006-05-12 | 2009-04-30 | Alexander Tobias Teichmann | Medication against breast cancer and related diseases |
US9138477B2 (en) | 2006-05-12 | 2015-09-22 | Mabel Gmbh | Uses for 4,17β-dihydroxyandrost-4-ene-3-one |
US9610292B2 (en) | 2006-05-12 | 2017-04-04 | Mabel Gmbh | Uses for 4,17β-dihydroxyandrost-4-ene-3-one |
WO2008065369A3 (en) * | 2006-11-28 | 2008-09-25 | Sunil Chopra | A bleomycin preparation for use against skin tumours |
WO2008065369A2 (en) * | 2006-11-28 | 2008-06-05 | Sunil Chopra | A bleomycin preparation for use against skin tumours |
GB2595502A (en) * | 2020-05-28 | 2021-12-01 | Chopra Sunil | Compounds, compositions and methods for the treatment or prevention of hair loss |
WO2021240163A1 (en) | 2020-05-28 | 2021-12-02 | Sunil Chopra | Compounds, compositions and methods for the treatment or prevention of hair loss |
GB2595502B (en) * | 2020-05-28 | 2023-01-11 | Chopra Sunil | Compounds, compositions and methods for the treatment or prevention of hair loss |
Also Published As
Publication number | Publication date |
---|---|
GB2398495B (en) | 2007-08-22 |
GB0301562D0 (en) | 2003-02-26 |
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Legal Events
Date | Code | Title | Description |
---|---|---|---|
PE20 | Patent expired after termination of 20 years |
Expiry date: 20230122 |