CN110638795A - Inhalable medicine and preparation method thereof - Google Patents
Inhalable medicine and preparation method thereof Download PDFInfo
- Publication number
- CN110638795A CN110638795A CN201911081437.1A CN201911081437A CN110638795A CN 110638795 A CN110638795 A CN 110638795A CN 201911081437 A CN201911081437 A CN 201911081437A CN 110638795 A CN110638795 A CN 110638795A
- Authority
- CN
- China
- Prior art keywords
- inhalable
- polyamino acid
- medicine
- inhalable medicament
- coating layer
- 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.)
- Pending
Links
- 239000003814 drug Substances 0.000 title claims abstract description 61
- 238000002360 preparation method Methods 0.000 title claims abstract description 9
- 239000007788 liquid Substances 0.000 claims abstract description 23
- 239000002253 acid Substances 0.000 claims abstract description 22
- 239000011247 coating layer Substances 0.000 claims abstract description 16
- 239000000126 substance Substances 0.000 claims abstract description 14
- 239000000243 solution Substances 0.000 claims abstract description 13
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims abstract description 12
- 238000010521 absorption reaction Methods 0.000 claims abstract description 7
- 239000012876 carrier material Substances 0.000 claims abstract description 7
- 239000011248 coating agent Substances 0.000 claims abstract description 7
- 238000000576 coating method Methods 0.000 claims abstract description 7
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 claims abstract description 6
- 239000011259 mixed solution Substances 0.000 claims abstract description 6
- 239000000203 mixture Substances 0.000 claims abstract description 6
- 238000005507 spraying Methods 0.000 claims abstract description 6
- 229940079593 drug Drugs 0.000 claims description 12
- 239000002245 particle Substances 0.000 claims description 7
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims description 5
- 239000004472 Lysine Substances 0.000 claims description 5
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 claims description 5
- 229920001577 copolymer Polymers 0.000 claims description 5
- 229930182830 galactose Natural products 0.000 claims description 5
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 claims description 4
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 claims description 4
- LKDRXBCSQODPBY-AMVSKUEXSA-N L-(-)-Sorbose Chemical compound OCC1(O)OC[C@H](O)[C@@H](O)[C@@H]1O LKDRXBCSQODPBY-AMVSKUEXSA-N 0.000 claims description 4
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 claims description 4
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 claims description 4
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 claims description 4
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims description 4
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 claims description 4
- MUPFEKGTMRGPLJ-RMMQSMQOSA-N Raffinose Natural products O(C[C@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](O[C@@]2(CO)[C@H](O)[C@@H](O)[C@@H](CO)O2)O1)[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 MUPFEKGTMRGPLJ-RMMQSMQOSA-N 0.000 claims description 4
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 claims description 4
- 229930006000 Sucrose Natural products 0.000 claims description 4
- MUPFEKGTMRGPLJ-UHFFFAOYSA-N UNPD196149 Natural products OC1C(O)C(CO)OC1(CO)OC1C(O)C(O)C(O)C(COC2C(C(O)C(O)C(CO)O2)O)O1 MUPFEKGTMRGPLJ-UHFFFAOYSA-N 0.000 claims description 4
- WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 claims description 4
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 claims description 4
- 239000008101 lactose Substances 0.000 claims description 4
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 claims description 4
- MUPFEKGTMRGPLJ-ZQSKZDJDSA-N raffinose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO[C@@H]2[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO)O2)O)O1 MUPFEKGTMRGPLJ-ZQSKZDJDSA-N 0.000 claims description 4
- 239000005720 sucrose Substances 0.000 claims description 4
- 238000000034 method Methods 0.000 claims description 3
- 230000009286 beneficial effect Effects 0.000 abstract description 2
- QNVKOSLOVOTXKF-UHFFFAOYSA-N 4-[(2-amino-3,5-dibromophenyl)methylamino]cyclohexan-1-ol;hydron;chloride Chemical compound Cl.NC1=C(Br)C=C(Br)C=C1CNC1CCC(O)CC1 QNVKOSLOVOTXKF-UHFFFAOYSA-N 0.000 description 2
- 229960000985 ambroxol hydrochloride Drugs 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- 230000009885 systemic effect Effects 0.000 description 2
- 206010006482 Bronchospasm Diseases 0.000 description 1
- 208000030453 Drug-Related Side Effects and Adverse reaction Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 206010070863 Toxicity to various agents Diseases 0.000 description 1
- 238000005054 agglomeration Methods 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 230000007885 bronchoconstriction Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 230000009982 effect on human Effects 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 231100000989 no adverse effect Toxicity 0.000 description 1
- 208000023504 respiratory system disease Diseases 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 230000001839 systemic circulation Effects 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
Classifications
-
- 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/5021—Organic macromolecular compounds
- A61K9/5031—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poly(lactide-co-glycolide)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
-
- 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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/007—Pulmonary tract; Aromatherapy
- A61K9/0073—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy
- A61K9/0075—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy for inhalation via a dry powder inhaler [DPI], e.g. comprising micronized drug mixed with lactose carrier particles
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Public Health (AREA)
- Pulmonology (AREA)
- Otolaryngology (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Medicinal Preparation (AREA)
Abstract
An inhalable medicine comprises liquid active medicine, carrier substance, and coating layer. The preparation method comprises the following steps: (1) grinding carrier material to 500-3000 nm, adding liquid active medicine for full absorption; (2) dissolving polyamino acid in glycol to obtain polyamino acid solution; (3) and (3) respectively and simultaneously spraying the mixture in the step (1) and the mixed solution in the step (2) into a freeze dryer to realize coating, so as to obtain the inhalable medicament. The beneficial effect is that the problem that the existing liquid medicine is difficult to realize the absorbability is solved.
Description
Technical Field
The invention belongs to the field of biological medicine, and particularly relates to an inhalable medicine.
Background
Currently, drug delivery via inhalation has been used for the treatment of certain respiratory disease states, such as infection, inflammation, or bronchoconstriction, and has also proven to be the preferred approach to achieve sufficiently high drug levels. In some cases, certain medicaments delivered via inhalation may produce fewer systemic side effects when inhaled. In another aspect, drugs for systemic activity can be delivered via inhalation to take advantage of the high surface area of the lungs, providing rapid drug absorption into the systemic circulation without the first pass metabolic effects associated with oral administration. In some cases, delivery of the agent to the lung may be for the convenience of the patient or healthcare provider. The usual way of using the drug is to grind the drug and the hydrophobic substance together to a certain particle size, thereby achieving inhalation of the drug. However, many medicaments are liquids, easily form large droplets, are easily absorbed in the nostrils, and are difficult to achieve effective inhalation.
Disclosure of Invention
The invention mainly aims to provide an inhalable medicament and a preparation method thereof, and solves the problem that the existing liquid medicament is difficult to realize inhalable.
In order to achieve the technical effects, the invention adopts the following technical scheme:
an inhalable medicine comprises liquid active medicine, carrier substance, and coating layer.
The liquid active drug is a liquid which is non-reactive with the carrier substance and the coating layer.
The carrier substance is at least one of galactose, lactose, sucrose, raffinose, maltose and sorbose.
The coating layer is a copolymer of two of proline, lysine and phenylalanine which are used as the polyamino acid, and the molecular weight is 12000-15000;
the preparation method of the inhalable medicine comprises the following steps:
(1) grinding carrier material to 500-3000 nm, adding liquid active medicine for full absorption;
(2) dissolving polyamino acid in glycol to obtain polyamino acid solution;
(3) and (3) respectively and simultaneously spraying the mixture in the step (1) and the mixed solution in the step (2) into a freeze dryer to realize coating, so as to obtain the inhalable medicament.
The viscosity of the polyamino acid solution is 9-10 poise.
The particle size of the inhalable medicine is 2-5 microns.
The invention has the beneficial effects that: (1) the coating layer has hydrophobicity, can not easily agglomerate and can be effectively absorbed.
(2) The coating layer has degradability, and can gradually release the drug and reduce the drug toxicity.
Detailed Description
For further understanding of the present invention, the following embodiments are provided to illustrate the technical solutions of the present invention in detail, and the scope of the present invention is not limited by the following embodiments.
An inhalable medicine comprises liquid active medicine, carrier substance, and coating layer.
The liquid active drug is a liquid which is non-reactive with the carrier substance and the coating layer.
The carrier substance is at least one of galactose, lactose, sucrose, raffinose, maltose and sorbose, can be absorbed by human body, and has no adverse effect on human body.
The coating layer is a copolymer of the two of proline, lysine and phenylalanine as the polyamino acid, has the molecular weight of 12000-15000, has hydrophobicity and degradability, can avoid agglomeration, and slows down the toxicity caused by quick release of the medicament; the preparation method of the inhalable medicine comprises the following steps:
(1) grinding carrier material to 500-3000 nm, adding liquid active medicine for full absorption;
(2) dissolving polyamino acid in glycol to obtain polyamino acid solution;
(3) and (3) respectively and simultaneously spraying the mixture in the step (1) and the mixed solution in the step (2) into a freeze dryer to realize coating, so as to obtain the inhalable medicament.
The viscosity of the polyamino acid solution is 9-10 poise, the viscosity is proper, and good coating can be formed.
The particle size of the inhalable medicine is 2-5 microns, the particle size distribution range is small, and the inhalable can be realized.
Example 1
An inhalable medicine comprises liquid active medicine, carrier substance, and coating layer.
The liquid active drug is ambroxol hydrochloride.
The carrier material is galactose.
The coating layer is a copolymer of proline and lysine as the polyamino acid, and the molecular weight is 15000;
the preparation method of the inhalable medicine comprises the following steps:
(1) grinding carrier material to 500 nm, adding liquid active medicine for full absorption;
(2) dissolving polyamino acid in glycol to obtain polyamino acid solution;
(3) and (3) respectively and simultaneously spraying the mixture in the step (1) and the mixed solution in the step (2) into a freeze dryer to realize coating, so as to obtain the inhalable medicament.
The viscosity of the polyamino acid solution is 10 poise.
The particle size of the inhalable medicine is 2-5 microns.
Example 2
An inhalable medicine comprises liquid active medicine, carrier substance, and coating layer.
The liquid active drug is ambroxol hydrochloride.
The carrier substance is at least one of galactose, lactose, sucrose, raffinose, maltose and sorbose.
The coating layer is a copolymer of two of proline, lysine and phenylalanine as the polyamino acid, and the molecular weight is 12000; the preparation method of the inhalable medicine comprises the following steps:
(1) grinding carrier material to 3000 nm, adding liquid active medicine for full absorption;
(2) dissolving polyamino acid in glycol to obtain polyamino acid solution;
(3) and (3) respectively and simultaneously spraying the mixture in the step (1) and the mixed solution in the step (2) into a freeze dryer to realize coating, so as to obtain the inhalable medicament.
The viscosity of the polyamino acid solution is 9 poise.
The particle size of the inhalable medicine is 2-5 microns.
The foregoing illustrates and describes the principles, general features, and advantages of the present invention. It should be understood by those skilled in the art that the above embodiments do not limit the scope of the present invention in any way, and all technical solutions obtained by using equivalent substitution methods fall within the scope of the present invention.
Claims (7)
1. An inhalable medicament, comprising: comprises liquid active medicine, carrier substance and coating layer.
2. An inhalable medicament as claimed in claim 1, characterised in that: the liquid active drug is a liquid which is non-reactive with the carrier substance and the coating layer.
3. An inhalable medicament as claimed in claim 1, characterised in that: the carrier substance is at least one of galactose, lactose, sucrose, raffinose, maltose and sorbose.
4. An inhalable medicament as claimed in claim 1, characterised in that: the coating layer is a copolymer of two of proline, lysine and phenylalanine which are used as the polyamino acid, and the molecular weight is 12000-15000.
5. A process for the preparation of an inhalable medicament as claimed in claim 1, wherein: the method comprises the following steps:
(1) grinding carrier material to 500-3000 nm, adding liquid active medicine for full absorption;
(2) dissolving polyamino acid in glycol to obtain polyamino acid solution;
(3) and (3) respectively and simultaneously spraying the mixture in the step (1) and the mixed solution in the step (2) into a freeze dryer to realize coating, so as to obtain the inhalable medicament.
6. An inhalable medicament as claimed in any one of claims 1 to 5, characterised in that: the viscosity of the polyamino acid solution is 9-10 poise.
7. An inhalable medicament as claimed in any one of claims 1 to 5, characterised in that: the particle size of the inhalable medicine is 2-5 microns.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201911081437.1A CN110638795A (en) | 2019-11-07 | 2019-11-07 | Inhalable medicine and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201911081437.1A CN110638795A (en) | 2019-11-07 | 2019-11-07 | Inhalable medicine and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN110638795A true CN110638795A (en) | 2020-01-03 |
Family
ID=68995636
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201911081437.1A Pending CN110638795A (en) | 2019-11-07 | 2019-11-07 | Inhalable medicine and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN110638795A (en) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101325945A (en) * | 2005-12-12 | 2008-12-17 | 雅戈泰克股份公司 | Powder compositions for inhalation |
-
2019
- 2019-11-07 CN CN201911081437.1A patent/CN110638795A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101325945A (en) * | 2005-12-12 | 2008-12-17 | 雅戈泰克股份公司 | Powder compositions for inhalation |
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| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20200103 |
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| WD01 | Invention patent application deemed withdrawn after publication |