GB2413075A - Liquids containing suspended water soluble glass particles - Google Patents
Liquids containing suspended water soluble glass particles Download PDFInfo
- Publication number
- GB2413075A GB2413075A GB0504501A GB0504501A GB2413075A GB 2413075 A GB2413075 A GB 2413075A GB 0504501 A GB0504501 A GB 0504501A GB 0504501 A GB0504501 A GB 0504501A GB 2413075 A GB2413075 A GB 2413075A
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- GB
- United Kingdom
- Prior art keywords
- particles
- formulation according
- liquid
- density
- formulation
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 239000002245 particle Substances 0.000 title claims abstract description 40
- 239000007788 liquid Substances 0.000 title claims abstract description 24
- NTHWMYGWWRZVTN-UHFFFAOYSA-N sodium silicate Chemical compound [Na+].[Na+].[O-][Si]([O-])=O NTHWMYGWWRZVTN-UHFFFAOYSA-N 0.000 title description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 title description 2
- 239000011521 glass Substances 0.000 claims abstract description 20
- 229910000389 calcium phosphate Inorganic materials 0.000 claims abstract description 5
- 239000001506 calcium phosphate Substances 0.000 claims abstract description 5
- 235000011010 calcium phosphates Nutrition 0.000 claims abstract description 5
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 claims abstract description 5
- GVGCUCJTUSOZKP-UHFFFAOYSA-N nitrogen trifluoride Chemical compound FN(F)F GVGCUCJTUSOZKP-UHFFFAOYSA-N 0.000 claims abstract description 3
- QTJXVIKNLHZIKL-UHFFFAOYSA-N sulfur difluoride Chemical compound FSF QTJXVIKNLHZIKL-UHFFFAOYSA-N 0.000 claims abstract description 3
- 150000001413 amino acids Chemical class 0.000 claims abstract 2
- 150000007942 carboxylates Chemical class 0.000 claims abstract 2
- 229910052751 metal Inorganic materials 0.000 claims abstract 2
- 239000002184 metal Substances 0.000 claims abstract 2
- 239000000203 mixture Substances 0.000 claims description 20
- 238000009472 formulation Methods 0.000 claims description 16
- 239000004480 active ingredient Substances 0.000 claims description 8
- 239000000725 suspension Substances 0.000 claims description 8
- 229960005486 vaccine Drugs 0.000 claims description 8
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 4
- 238000001694 spray drying Methods 0.000 claims description 3
- TXEYQDLBPFQVAA-UHFFFAOYSA-N tetrafluoromethane Chemical compound FC(F)(F)F TXEYQDLBPFQVAA-UHFFFAOYSA-N 0.000 claims description 3
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 2
- 239000005864 Sulphur Substances 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- 150000001412 amines Chemical class 0.000 claims description 2
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 2
- 125000003118 aryl group Chemical group 0.000 claims description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 2
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 2
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 2
- 238000004108 freeze drying Methods 0.000 claims description 2
- 125000000524 functional group Chemical group 0.000 claims description 2
- 238000000227 grinding Methods 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims description 2
- -1 hydrofluorothioether Chemical compound 0.000 claims description 2
- 229910052757 nitrogen Inorganic materials 0.000 claims description 2
- 239000001301 oxygen Substances 0.000 claims description 2
- 229910052760 oxygen Inorganic materials 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 1
- 229920001774 Perfluoroether Polymers 0.000 abstract 1
- 239000013543 active substance Substances 0.000 abstract 1
- 230000002776 aggregation Effects 0.000 abstract 1
- 238000004220 aggregation Methods 0.000 abstract 1
- UJMWVICAENGCRF-UHFFFAOYSA-N oxygen difluoride Chemical compound FOF UJMWVICAENGCRF-UHFFFAOYSA-N 0.000 abstract 1
- 239000010702 perfluoropolyether Substances 0.000 abstract 1
- 239000008194 pharmaceutical composition Substances 0.000 abstract 1
- 150000002170 ethers Chemical class 0.000 description 7
- 238000000034 method Methods 0.000 description 6
- 229920006926 PFC Polymers 0.000 description 3
- 102100038567 Properdin Human genes 0.000 description 3
- 230000002209 hydrophobic effect Effects 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 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 description 2
- 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 description 2
- 230000008901 benefit Effects 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 239000004005 microsphere Substances 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 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 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- 241000590428 Panacea Species 0.000 description 1
- 239000011149 active material Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 239000004411 aluminium Substances 0.000 description 1
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 1
- 229910021502 aluminium hydroxide Inorganic materials 0.000 description 1
- 229940124326 anaesthetic agent Drugs 0.000 description 1
- 239000003599 detergent Substances 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000003193 general anesthetic agent Substances 0.000 description 1
- SPSXSWRZQFPVTJ-ZQQKUFEYSA-N hepatitis b vaccine Chemical compound C([C@H](NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)CCSC)C(=O)N[C@@H](CC1N=CN=C1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C(C)C)C(=O)OC(=O)CNC(=O)CNC(=O)[C@H](C)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@@H](N)CCCNC(N)=N)C1=CC=CC=C1 SPSXSWRZQFPVTJ-ZQQKUFEYSA-N 0.000 description 1
- 229940124736 hepatitis-B vaccine Drugs 0.000 description 1
- 230000005660 hydrophilic surface Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- 229950011087 perflunafene Drugs 0.000 description 1
- UWEYRJFJVCLAGH-IJWZVTFUSA-N perfluorodecalin Chemical compound FC1(F)C(F)(F)C(F)(F)C(F)(F)[C@@]2(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)[C@@]21F UWEYRJFJVCLAGH-IJWZVTFUSA-N 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 229920001084 poly(chloroprene) Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000005437 stratosphere Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 239000005436 troposphere Substances 0.000 description 1
- 238000010792 warming Methods 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
-
- 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
- A61K47/24—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
-
- 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
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Dermatology (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Medicinal Preparation (AREA)
- Glass Compositions (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Physical Or Chemical Processes And Apparatus (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
A pharmaceutical composition comprising a biologically active agent preserved in particulate form, in particular a glass or amorphous particle, such as a sugar, a metal carboxylate, an amino acid or calcium phosphate, wherein said particles are suspended in at least one of a hydrofluoroether, a perfluoroether, a hydrofluoroamine, a perfluoroamine, a hydrofluorothioether, a perfluorothioether, a hydrofluoropolyether or a perfluoropolyether. The use of such fluorinated liquid media overcomes the problem of aggregation of particles and also is environmentally friendly.
Description
24 1 3075
LIQUIDS CONTAINING SUSPENDED GLASS PARTICLES
This invention relates to a formulation comprising an active ingredient preserved in particles of a glassy or amorphous substance suspended in a liquid.
It is well known that sugar glass has an ability to preserve certain organic, biological, botanical and protein materials and there is a considerable amount of literature devoted to theoretical proposals for using this property of sugar glass to preserve pharmaceutical products, particularly vaccines. Other glassy substances have been shown to have a similar preservative effect.
Because the most commonly accepted method of administering vaccines is by injection it has been proposed, eg in patent specification WO 02/32402 (Roser) to suspend particles of water soluble glass, containing the vaccine, in a liquid (a perfluorocarbon such as perfluorodecalin) so as to create an injectable formulation. Perfluorocarbons were proposed because they are very stable and know as being safe for pharmaceutical and medical uses. It was also proposed in patent specification PCT WO 02/32402 to increase the density of the glass by adding calcium phosphate (density about 2.7 to 2.8) to the sugar glass (density about 1.5) so as to produce particles matched to the 1.97 density value of the liquid in which they were to be suspended; thereby keeping them in suspension. - 2
The above techniques, show great promise, but the complete stability of perfluorocarbons mean that they are persistent in the troposphere and, if used in large amounts could actually contribute to global warming. In addition hydrophilic glass microsphere particles show a slight tendency to aggregate in perfluorocarbons, which are intensely hydrophobic.
According to this invention there is provided a formulation comprising an active ingredient preserved in glassy or amorphous particles, the particles being suspended in a liquid in which at least one component comprises a hydrofluoroether, perfluroether, hydrofluoroamine, perfluoroamine, hydrofluorothioether, perfluorothioether hydrofluoropolyether, perfluorpolyether or a general formula Rl-X-R2 or I S Rl-X-(CF2Y)n(CF2CF2Z)m-R2 or R I -[(X-CF-R2)n-(X- CF2)m]0R3 where X, Y and Z are defined as O (oxygen), an ether, NR3 (N=nitrogen), an amine or S (sulphur); and each of Rl, R2 and R3 are defined as a non fluorinated, partially fluorinated or fully fluorinated alkyl, cycloalkyl, aryl or arylalkyl group or an organic functional group, halogen group or cyano group.
Preferably, hydrofluoroethers or hydrofluoropolyethers are considered ideal and accordingly there is provided a formulation comprising an active ingredient preserved in glassy or amorphous particles, the particles being suspended in a liquid comprising a hydrofluoroether or hydrofluoropolyether.
The inventors discovered that when mixed glass particles were added to a hydrofluoroether or hydrofluoropolyether, they dispersed astonishingly easily to form a milky suspension with little or no signs of clumping of the glass particles even after the suspension had been left for some time.
The inventors have now developed the theory that the glass particles have a hydrophilic surface whilst the perfluorocarbons, previously used, are intensely hydrophobic. For this reason, in the earlier experiments with perfluorocarbons, it is now believed that the glass particles had a tendency to clump together because they are repelled by the hydrophobic nature of the perfluorocarbon.
Fluorinated ethers, behave somewhat more like a detergent, facilitating dispersion of the particles.
A number of fluorinated ethers are presently being administered as anaesthetic agents via inhalation during surgical procedures. The relatively large quantities (up to 200 gms) which are used during surgical procedures indicates the low- toxicity of the group.
Additionally, their densities are ideally matched to the densities of glasses used in the formulations described above. For example, referring to the designations of 3M Limited: HFE 7500 has a density of 1.61, - 4 HFE 7200 has a density of 1.43, and HFE 7100 has a density of 1.52.
These values are, co-incidentally similar to the density of sugar glass, which is about 1.5.
An additional benefit of using the invention is that fluorinated ethers, whilst being highly stable in normal conditions, are unstable when exposed to strong ultraviolet radiation such as is present in the stratosphere. This avoids a problem ] O associated with perfluorocarbons which are known to contribute to the damaging "greenhouse" effect when released into the atmosphere after use.
Yet another advantage of the invention is that fluorinated ethers are relatively inexpensive and are readily available at a high degree of purity, greater than 98%. This compares with PFCs for which a typical example might have a purity of only about 55%.
Because fluorinated ethers are so well matched with the glasses, it has become possible to adopt a new approach to density matching. Previously, the glass was formulated, by use of additives, to match its density to that of the liquid PFC.
However, it now becomes unnecessary to constrain the selection of the glass according to the need to achieve the correct density. The invention makes it possible to select the ideal glass/active ingredient composition; and then to mix - 5 a fluorinated ether possibly with the addition of small quantities of PFCs or other liquids so as to match the density of the liquid to the density of the particles. It even becomes practicable to take ready-made compositions of active ingredient preserved in a glassy substance; to grind it into particles and then to suspend it in a liquid matched to the density of the particles.
The densities of the particles and of the liquid do not have to be identical.
However, they should be sufficiently close that Brownian movement or other thermodynamic influences keep the particles in suspension.
Because the particles have been found to disperse so effectively in fluorinated ethers and other liquids referred to above, the need to make the particles as small as possible, so as to maintain a suspension, is now not as acute as before.
Specialist, modified spray drying techniques, which were previously thought by the inventors to be needed in order to achieve small particle size, are now unnecessary although the standard commercial spray drying process is still one possible technique for making the particles. However, alternative methods such as freeze drying or grinding would now also be practicable. It is only necessary that the particles should be sufficiently small to permit passage through a hypodermic syringe.
It is envisaged that the invention will normally be employed for the formulation of vaccines, therapeutic proteins or other medications for injection through the skin of a patient. However, other uses for the invention may be possible, eg for medicinal liquids which are administered orally or inhaled after atomising. It is also possible that there may be non-medicinal uses for the invention which is generally applicable to any situation where it is desired to preserve a biologically active material in a glassy solid and where there is a need for the composition to be presented in liquid form.
One way of performing the invention will now be described.
Sterile, bulk liquid hepatitis B vaccine with aluminium hydroxide adjuvant was obtained from Panacea Biotech of Delhi. This was mixed with sterile colloidal calcium phosphate suspension and raffinose solution in the correct proportions to give a single adult dose of 10 log vaccine in 50 milligrams of total solids. The proportion of calcium phosphate to raffinose was calculated to give solid glass particles with a density matching that of the hydrofluoroether HFE 7,500 of 1.61 Kg/L. While being constantly stirred by a magnetic stirrer, this suspension was pumped through a two fluid nozzle at the rate of 2 ml per minute with a nozzle gas flow of 2.5 Kg/hr. The resulting droplets were dried in the chamber of a GEA Niro SD Micro spray with a heated air flow of 30 Kg per hour. The outlet temperature was maintained at 90 C by regulating the inlet temperature keeping the feed flow rate constant. Product was collected in a sterile bottle and transferred to a laminar flow hood with class 100 air flow. Sterile HFE 7,500 was added at the rate of I ml per 100 mg of powder and agitated in a frequency - 7 sweep ultrasonic bath (Decon *** for 10 min to fully disperse the microspheres.
In the flow hood, the liquid was dispensed in 0.6 ml volumes into sterile 2 ml serum vials, plugged with neoprene stoppers and sealed with aluminium caps.
The vaccine vials were used to set up a study of the in vitro stability of the vaccine at various storage temperatures. - 8
Claims (11)
1. A formulation comprising an active ingredient preserved in glassy or amorphous particles, the particles being suspended in a liquid in which at least one component comprises a hydrofluoroether, perfluroether, hydrofluoroamine, perfluoroamine, hydrofluorothioether, perfluorothioether hydrofluoropolyether, perfluorpolyether or a general formula Rl-X-R2 or Rl-X-(CF2Y)n(CF2CF2Z)m-R2 or Rl-[(X-CF-R2)n-(X-CF2)m] 0R3 where X, Y and Z are defined as O (oxygen), an ether, NR3 (N=nitrogen) , an amine or S (sulphur); and each of Rl, R2 and R3 are defined as a non fluorinated, partially fluorinated or fully fluorinated alkyl, cycloalkyl, aryl or arylalkyl group or an organic functional group, halogen group or cyano group.
2. A formulation according to Claim I in which the particles contain a sugar glass or a glass which is a mixture of sugar, metal carboxylate, amino acid and or calcium phosphate or any combination of these.
3. A formulation according to Claim I or 2 in which the particles have a density which is matched to the density of the liquid sufficiently closely that the particles will remain in suspension under normal conditions.
4. A formulation according to any preceding claim in which the liquid contains different components specified in claim I mixed in proportions to give a required density.
5. A formulation according to any preceding claim in which the liquid contains a perfluorocarbon mixed with one or more components specified in claim 1. - 9 -
6. A formulation according to any preceding claim in which the active ingredient is a vaccine.
7. A formulation according to any preceding claim in which the particles are made by spray drying
8. A formulation according to any one of Claims I to 6 in which the particles are made by freeze drying.
9. A formulation according to any one of Claims 1 to 6 in which the particles are made by grinding.
10. A method of making a formulation according to Claim 4 or 5 including the step of selecting liquids to give the required density matching properties and mixing them with the particles.
11. A formulation comprising an active ingredient preserved in glassy or amorphous particles, the particles being suspended in a liquid comprising a hydrofluoroether.
Priority Applications (15)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
ES05731023T ES2339783T3 (en) | 2004-04-13 | 2005-04-13 | LIQUIDS CONTAINING SUSTAINED VITREAS PARTICLES. |
DK05731023.7T DK1750668T3 (en) | 2004-04-13 | 2005-04-13 | Liquids containing suspended glass particles |
KR1020067022106A KR20070009639A (en) | 2004-04-13 | 2005-04-13 | Liquids containing suspended glass particles |
PT05731023T PT1750668E (en) | 2004-04-13 | 2005-04-13 | Liquids containing suspended glass particles |
AU2005232441A AU2005232441B2 (en) | 2004-04-13 | 2005-04-13 | Liquids containing suspended glass particles |
EP05731023A EP1750668B1 (en) | 2004-04-13 | 2005-04-13 | Liquids containing suspended glass particles |
AT05731023T ATE457717T1 (en) | 2004-04-13 | 2005-04-13 | LIQUIDS WITH SUSPENDED GLASS PARTICLES |
PCT/GB2005/050050 WO2005099669A1 (en) | 2004-04-13 | 2005-04-13 | Liquids containing suspended glass particles |
CN2005800110373A CN1942171B (en) | 2004-04-13 | 2005-04-13 | Liquids containing suspended glass particles |
DE602005019398T DE602005019398D1 (en) | 2004-04-13 | 2005-04-13 | LIQUIDS WITH SUSPENDED GLASS PARTICLES |
MXPA06011895A MXPA06011895A (en) | 2004-04-13 | 2005-04-13 | Liquids containing suspended glass particles. |
CA002562606A CA2562606A1 (en) | 2004-04-13 | 2005-04-13 | Liquids containing suspended glass particles |
US10/599,928 US20080026066A1 (en) | 2004-04-13 | 2005-04-13 | Liquids Containing Suspended Glass Particles |
RU2006137275/15A RU2363447C2 (en) | 2004-04-13 | 2005-04-13 | Liquid, containing suspended vitreous particles |
JP2007507853A JP2007532619A (en) | 2004-04-13 | 2005-04-13 | Liquid containing suspended glass particles |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GBGB0408199.8A GB0408199D0 (en) | 2004-04-13 | 2004-04-13 | Liquids containing suspended sugar glass particles |
Publications (3)
Publication Number | Publication Date |
---|---|
GB0504501D0 GB0504501D0 (en) | 2005-04-13 |
GB2413075A true GB2413075A (en) | 2005-10-19 |
GB2413075B GB2413075B (en) | 2009-01-21 |
Family
ID=32320732
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
GBGB0408199.8A Ceased GB0408199D0 (en) | 2004-04-13 | 2004-04-13 | Liquids containing suspended sugar glass particles |
GB0504501A Active GB2413075B (en) | 2004-04-13 | 2005-03-07 | Liquids containing suspended glass particles |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
GBGB0408199.8A Ceased GB0408199D0 (en) | 2004-04-13 | 2004-04-13 | Liquids containing suspended sugar glass particles |
Country Status (10)
Country | Link |
---|---|
CN (1) | CN1942171B (en) |
AT (1) | ATE457717T1 (en) |
DE (1) | DE602005019398D1 (en) |
DK (1) | DK1750668T3 (en) |
ES (1) | ES2339783T3 (en) |
GB (2) | GB0408199D0 (en) |
MX (1) | MXPA06011895A (en) |
PT (1) | PT1750668E (en) |
RU (1) | RU2363447C2 (en) |
ZA (1) | ZA200609158B (en) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2007026180A3 (en) * | 2005-08-31 | 2007-08-02 | Cambridge Biostability Ltd | Improvements in the stabilisation of biological materials |
US8821437B2 (en) | 2005-11-21 | 2014-09-02 | Nova Bio-Pharma Technologies Limited | Pharmaceutical device for the administration of substances to patients |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US9243626B2 (en) | 2012-11-19 | 2016-01-26 | Nordson Corporation | Adhesive dispensing system and method including a pump with integrated diagnostics |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH07258027A (en) * | 1994-03-16 | 1995-10-09 | Shiseido Co Ltd | Makeup cosmetic |
WO2002032402A1 (en) * | 2000-10-13 | 2002-04-25 | Cambridge Biostability Ltd. | Composition and method for stable injectable liquids |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6433040B1 (en) * | 1997-09-29 | 2002-08-13 | Inhale Therapeutic Systems, Inc. | Stabilized bioactive preparations and methods of use |
US6190701B1 (en) * | 1999-03-17 | 2001-02-20 | Peter M. Ronai | Composition and method for stable injectable liquids |
WO2001037804A2 (en) * | 1999-11-22 | 2001-05-31 | Universal Preservation Technologies, Inc. | Preservation and formulation of bioactive materials |
-
2004
- 2004-04-13 GB GBGB0408199.8A patent/GB0408199D0/en not_active Ceased
-
2005
- 2005-03-07 GB GB0504501A patent/GB2413075B/en active Active
- 2005-04-13 DK DK05731023.7T patent/DK1750668T3/en active
- 2005-04-13 PT PT05731023T patent/PT1750668E/en unknown
- 2005-04-13 RU RU2006137275/15A patent/RU2363447C2/en not_active IP Right Cessation
- 2005-04-13 DE DE602005019398T patent/DE602005019398D1/en active Active
- 2005-04-13 CN CN2005800110373A patent/CN1942171B/en not_active Expired - Fee Related
- 2005-04-13 MX MXPA06011895A patent/MXPA06011895A/en unknown
- 2005-04-13 AT AT05731023T patent/ATE457717T1/en not_active IP Right Cessation
- 2005-04-13 ES ES05731023T patent/ES2339783T3/en active Active
-
2006
- 2006-11-03 ZA ZA200609158A patent/ZA200609158B/en unknown
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
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JPH07258027A (en) * | 1994-03-16 | 1995-10-09 | Shiseido Co Ltd | Makeup cosmetic |
WO2002032402A1 (en) * | 2000-10-13 | 2002-04-25 | Cambridge Biostability Ltd. | Composition and method for stable injectable liquids |
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WPI Abatract Accession No 1995-379943/49 & JP 07258027 A * |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2007026180A3 (en) * | 2005-08-31 | 2007-08-02 | Cambridge Biostability Ltd | Improvements in the stabilisation of biological materials |
US8821437B2 (en) | 2005-11-21 | 2014-09-02 | Nova Bio-Pharma Technologies Limited | Pharmaceutical device for the administration of substances to patients |
Also Published As
Publication number | Publication date |
---|---|
CN1942171B (en) | 2011-04-06 |
RU2006137275A (en) | 2008-05-20 |
ES2339783T3 (en) | 2010-05-25 |
GB2413075B (en) | 2009-01-21 |
GB0408199D0 (en) | 2004-05-19 |
MXPA06011895A (en) | 2007-11-20 |
CN1942171A (en) | 2007-04-04 |
PT1750668E (en) | 2010-04-07 |
GB0504501D0 (en) | 2005-04-13 |
DK1750668T3 (en) | 2010-05-10 |
RU2363447C2 (en) | 2009-08-10 |
ZA200609158B (en) | 2008-06-25 |
DE602005019398D1 (en) | 2010-04-01 |
ATE457717T1 (en) | 2010-03-15 |
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