WO2009157010A1 - Système de distribution de médicament par voie intraveineuse - Google Patents
Système de distribution de médicament par voie intraveineuse Download PDFInfo
- Publication number
- WO2009157010A1 WO2009157010A1 PCT/IN2008/000754 IN2008000754W WO2009157010A1 WO 2009157010 A1 WO2009157010 A1 WO 2009157010A1 IN 2008000754 W IN2008000754 W IN 2008000754W WO 2009157010 A1 WO2009157010 A1 WO 2009157010A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- sodium
- drug delivery
- delivery system
- intravenous drug
- paracetamol
- Prior art date
Links
- 238000001990 intravenous administration Methods 0.000 title claims abstract description 22
- 238000012377 drug delivery Methods 0.000 title claims description 11
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 claims abstract description 25
- 229960005489 paracetamol Drugs 0.000 claims abstract description 24
- 229960001193 diclofenac sodium Drugs 0.000 claims abstract description 15
- JGMJQSFLQWGYMQ-UHFFFAOYSA-M sodium;2,6-dichloro-n-phenylaniline;acetate Chemical compound [Na+].CC([O-])=O.ClC1=CC=CC(Cl)=C1NC1=CC=CC=C1 JGMJQSFLQWGYMQ-UHFFFAOYSA-M 0.000 claims abstract description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 12
- 238000000034 method Methods 0.000 claims abstract description 10
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 22
- 239000003814 drug Substances 0.000 claims description 12
- 239000011780 sodium chloride Substances 0.000 claims description 12
- 229940079593 drug Drugs 0.000 claims description 11
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 9
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 6
- 239000003795 chemical substances by application Substances 0.000 claims description 6
- 238000002360 preparation method Methods 0.000 claims description 6
- 229910052708 sodium Inorganic materials 0.000 claims description 6
- 239000011734 sodium Substances 0.000 claims description 6
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- ZGTMUACCHSMWAC-UHFFFAOYSA-L EDTA disodium salt (anhydrous) Chemical group [Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O ZGTMUACCHSMWAC-UHFFFAOYSA-L 0.000 claims 2
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- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- PPASLZSBLFJQEF-RKJRWTFHSA-M sodium ascorbate Substances [Na+].OC[C@@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RKJRWTFHSA-M 0.000 description 1
- 235000010378 sodium ascorbate Nutrition 0.000 description 1
- 229960005055 sodium ascorbate Drugs 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
- PPASLZSBLFJQEF-RXSVEWSESA-M sodium-L-ascorbate Chemical compound [Na+].OC[C@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RXSVEWSESA-M 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000002693 spinal anesthesia Methods 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 238000012414 sterilization procedure Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000005979 thermal decomposition reaction Methods 0.000 description 1
- 229940035024 thioglycerol Drugs 0.000 description 1
- CWERGRDVMFNCDR-UHFFFAOYSA-N thioglycolic acid Chemical compound OC(=O)CS CWERGRDVMFNCDR-UHFFFAOYSA-N 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 231100000027 toxicology Toxicity 0.000 description 1
- 230000007723 transport mechanism Effects 0.000 description 1
- 210000003462 vein Anatomy 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
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
- A61K31/167—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
-
- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/196—Carboxylic acids, e.g. valproic acid having an amino group the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil
-
- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
-
- 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
Definitions
- Filed of invention is related to the drug delivery system. More particularly field is related to the pharamaceuical and diclofenac sodium forumaltion for the intravenous administration of a drug, Most particularly invention is related a pharmaceutical composition for intravenous administration containing paracetamol and diclofenac sodium in an aqueous base.
- a route of administration is the path by which a drug, fluid, poison or other substance is brought into contact with the body.
- a substance must be transported from the site of entry to the part, of the body where its action is desired to take place (even if this only means penetration through the into the skin).
- using the body's transport mechanisms for this purpose can be far from trivial,
- the pharmacokinetics properties of a drug that is, those related to processes of uptake, distribution, and elimination) are critically influenced by the route of administration.
- Routes of administration can broadly be divided into;
- intraarterial into an artery
- vasoioditor drugs in the treatment of vasospam
- therobylotic drugs for treatment of embolisim
- intramuscular into muscle
- vaccines e.g. many vaccines , antibiotics, and long- term psychoactive agents
- intraosseous infusion (into the bone marrow) is, in effect, an indirect intravenous access because the bone marrow drains directly into the venous system. This route is occasionally used for drugs and fluids in emergency medicine and paediatrics when intravenous access is difficult.
- intrathecal into the spinal canal
- Paracetamol or acetaminophen is a widely-used analgesic and antipyretic, unlike aspirin it is not a very effective anti-inflammatory agent. It is well tolerated, lacks many of the side-effects of aspirin and is available over-the-counter so it is commonly used for the relief of fever headaches, and other minor aches and pains. Paracetamol is also useful in the management of more severe pain, where it allows lower dosages of additional non-steroidal anti-inflammatory drugs (NSAIDs) to be used, and thereby minimizing overall side-effects. It is also used in combination with opioid analgesics It is a major ingredient in numerous cold and flu medicationsintraperitoneai (infusion or injection into the peritoneum) e.g. peritoneal dialysis.
- NSAIDs non-steroidal anti-inflammatory drugs
- Diclofenac with various drug dose combinations is a non-steroidal antiinflammatory drug (NSAiD) taken ⁇ o reduce inflammation and as an analgesic reducing pain in conditions sucrvas arthritis or acute injury It can also be used to reduce menstrua!.
- NSAiD non-steroidal antiinflammatory drug
- the name is derived from its chemical name: 2-(2,6- dichloranilino) phenylacetic acid
- Diclofenac may also be a unique member of the NSAIDs.There is some evidence that diclofenac inhibits the lipoxygenase pathways, thus reducing formation of the leukotrienes ⁇ also pro-inflammatory autacoids). There is also speculation that diclofenac may inhibit phospholipase A 2 as part of its mechanism of action. These additional actions may explain the high potency of diclofenac - it is the most potent NSAiD on a broa ⁇ basis.
- composition for oral administration for the treatment of acute pain and inflammation comprises an inclusion complex of a non-steroidal anti-inflammatory drug or a pharmaceutically acceptable salt thereof and a cyclodextrin, and a physiologically acceptable alkali agent selected from the group consisting of alkali and alkaline earth metal carbonates, bicarbonates, phosphates and hydroxides, and water soluble amines, in an amount equivalent to between 2 and 30 molar equivalents inclusive of the non-steroidal anti-inflammatory drug, the alkali agent being capable of forming an alkaline diffusion layer around the composition in the grastrointestinal tract.
- United States Patent 6,028,222 discloses a combination liquid paracetamol combination. Novel stable paracetamoi compositions for use in therapeutic chemistry and specifically galenic pharmacy are disclosed.
- the compositions contain a solution of paracetamol in an aqueous solvent combined with a buffer having a pH of 4 to 8, and a frfee radical capturing agent.
- a water-insoluble inert gas is carefully bubbled through the aqueous solvent to remove oxygen from the medium.
- Said compositions may also be combined with a centrally or peripherally acting analgesic agent, and are provided as inject able compositions for relieving pain.
- An object of the invention is to design a direct injection method for the paracetamol and diclofenac sodium. Another object of the invention is to formulate intravenous formulation of the paracetamol and diclofenac sodium in combination. Yet another object of the invention is to prepare water based formulation of intravenous administration of the paracetamol and diclofenac sodium.
- Present invention is related to intravenous administration of the paracetamol and disclofe ⁇ ac sodium in combination, in this method paracetamol powder and diclofenac sodium are dissolved separately in the aqueous phase and suitable pH is adjusted by acid or base and this solution is directly administrated in the patients body though the direct injection.
- the subject in the methods described herein can be, e.g., a mammal, e.g., a human, mouse, rat, dog, cat, horse, cow, pig, or non-human primate.
- the subject is a juvenile human, e.g., a subject less than 7 years of age.
- pharmaceutically effective amount means that amount of a drug or pharmaceutical agent that will elicit the biological or medical response of a tissue, system, animal or human that is being sought by a researcher or clinician.
- compositions are preferably suitable for internal use and include an effective amount of a pharmacologically active compound of the invention, alone or in combination, with one or more pharmaceutically acceptable carriers!
- the compounds are especially useful in that they have very low, if any, toxicity.
- the method of administration of the paracetamol and diclofenac sodium in the present invention is through the intravenous route through an aqueous vehicle.
- the paracetamol is dissolved in water for injection.
- the injection thus prepared also contains adjuvants, buffers isotonic.
- Adjuvants are pharmacological or immunological agents that modify the effect of other agents (e.g., drugs, vaccines) while having few if any direct effects when given by themselves. In this sense, they are roughly analogous to chemical,
- Sodium sulfite sodium sulphite
- ⁇ t is also used as a presser to prevent dried fruit from discoloring, and for preserving meats, and is used in the same way as sodium thiosulfate to convert elemental halides to their respective acids
- PBS Phosphate buffered saline
- the buffer helps to maintain a constant pH
- the osmolarity and ion cone Potassium hydrogen phthalate, often called simply KHP, is a white or colorless, ionic soiid that is the monopotasssum salt of phthalic acid.
- the hydrogen is slightly acidic, and it is often used as a primary standard for acid-base titrations because it is solid and air-stable, making it easy to weigh accurately. It is, however, slightly hygroscopic and is generally kept in a desiccator before use. It is also used as a primary standard for calibrating pH meters because, besides the properties just mentioned, its pH in solution is very stable.
- KHP can be used as a buffering agent (in combination with HCI or NaOH depending on which side of pH 4.0 the buffer is to be) but should not be used as a buffer for decarboxylation reactions, as these will degrade the KHP and mop up the conjugation groups
- Stability of the aqueous solutions mentioned above does not solely depend on the choice of a given earner, ⁇ t also depends on other variables, such as careful adjustment of pH, removal of oxygen dissolved in the carrier and addition of a free radical antagonist or a free radical scavenger.
- Removal of dissolved oxygen is readily accomplished by bubbling an inert gas and preferably by bubbling nitrogen.
- the appropriate free radical antagonist is chosen among the derivatives of ascorbic acid, those derivatives bearing at least a thiol functional group and straight chain or . cyclic polyhydric compounds.
- Preferred ascorbic acid derivatives are D- or L-ascorbic acid, an alkali metal ascorbate, an alkaline earth metal ascorbate or even still an aqueous medium- soluble ascorbic acid ester.
- Free radical scavengers, bearing a thiol functional group may be an organic compound substituted by one or more thiol functional groups, of the aliphatic series such as cystein, acetylcy stein, thioglycollic acid and salts thereof, thiolactic acid and salts thereof, dithlothr ⁇ ltol, reduced glutathion, thiourea, thioglycerol, methionine and mercaptoethane sulfonic acid,
- the polyol used as a free radical scavenger is preferably a straight chain or a cyclic, polyhydroxy alcohol such as mannitol, sorbitol, inositol, isosorbide, glycerol, glucose and propylene-glycols.
- the ascorbic acid derivative currently preferred is sodium ascorbate.
- Preferred thiol functional group substituted derivatives are cystein, reduced-slate glutathion, N- acetylcystein and mercaptoethane sulfonic acid.
- free radical scavengers it may appear as convenient to combine several free radical scavengers as far as they are water-soluble and mutually compatible. Especially convenient free radical scavengers are mannitol, glucose, sorbitol or even glycerol. These may be readily combined.
- Sodium chloride also known as common salt, table salt, or halite is a chemical compound with the formula Sodium chloride is the salt most responsible for the salinity.
- the gas that is bubbled into the solution to drive out oxygen may be nitrogen or carbon dioxide or still an inert gas. Nitrogen is favoured.
- lsotonicity of the preparation may be achieved by adding an appropriate quantity of sodium chloride, glucose, Sevulose or postassium chloride, or calcium chloride, or calcium gluconoglucoheptonate, or mixtures thereof.
- the preferred isotonizing agent is sodium chloride.
- the buffer used is a buffer compatible with parenteral administration in humans, the pH of which roay be adjusted between 4 and 8.
- Preferred buffers are based on alkali metal alkaline earth metal acetates or phosphates.
- a more preferred buffer is sodium acetate/hydrogene phosphate adjusted to the required pH with hydrochloric acid or sodium hydroxide.
- the concentration of such a buffer may be comprised between 0.1 and 10 mg/ml. The preferred concentration is confined in the range of 0.25 to 5 mg/ml.
- antioxidants such as glutathion are broken down JFIALAIRC A. et al., J. Pharm. Biomed. Anal., vol. 10, No 6, pp. 457-460 (1992)].
- the breakdown of reduced giutathion during heat treatment sterilization ranges from 40 to 77% depending on the selected temperature conditions.
- Addition of complexing agents to aqueous solutions inhibits thermal decomposition of thiol derivatives, such as glutathion, edentate sodium.
- Liquid pharmaceutical compositions according to the invention are preferably compositions intended for injection.
- the paracetamol content of the solution may range from 2 mg/ml to 50 mg/ml in case of so calied dilute solutions, i.e. that can be directly infused by intravenous route and from 60 mg/ml to 350 mg/ml where so-called concentrated solution are considered, i.e. either intended for direct injection by intravenous or intramuscular route, or intended to be diluted prior to slow infusion administration.
- the preferred concentration are comprised between 5 and 20 mg/ml for dilute solutions and between 100 and 250 mg/ml for concentrated solutions or mostly the amount which is pharmaceutically effective amount is used for ihe preparation of the said formulation.
- compositions according to the invention may further contain another active ingredient that enhances the specific effect of paracetamol.
- compositions according to the invention diclofenac such as for exampie a diclofenac sodium
- isotonic may refer to
- Concentration of the solution usually match those of the human body (isotonic). The process is earned at the different temperatures. The activity increases after the direct administration of the paracetamol and patient gains immediate relief.
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pain & Pain Management (AREA)
- Dermatology (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
L'invention concerne l'administration de paracétamol & sodium de diclofénac par voie intraveineuse dans un véhicule aqueux. On dissout le paracétamol & sodium de diclofénac dans de l'eau aux fins d'injection à l'aide d'éléments passifs assurant une fonction tampon, isotonique, etc. L'opération est conduite à différentes températures. L'activité du paracétamol & sodium de diclofénac augmente après dissolution sous forme aqueuse, et l'on procure ainsi un confort accru au patient.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
IN1529DE2008 | 2008-06-25 | ||
IN1529/DEL/2008 | 2008-06-25 |
Publications (1)
Publication Number | Publication Date |
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WO2009157010A1 true WO2009157010A1 (fr) | 2009-12-30 |
Family
ID=41444113
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/IN2008/000754 WO2009157010A1 (fr) | 2008-06-25 | 2008-11-05 | Système de distribution de médicament par voie intraveineuse |
Country Status (1)
Country | Link |
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WO (1) | WO2009157010A1 (fr) |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20170304357A1 (en) * | 2016-03-30 | 2017-10-26 | Baylor University | Nutraceutical containing an oxygen-enabled composition |
US10137146B2 (en) * | 2016-03-30 | 2018-11-27 | Baylor University | Oxygen-enabled composition |
US10369101B2 (en) | 2013-03-15 | 2019-08-06 | Latitude Pharmaceuticals Inc. | Parenteral diclofenac composition |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6028222A (en) * | 1996-08-05 | 2000-02-22 | Scr Pharmatop | Stable liquid paracetamol compositions, and method for preparing same |
US20060293228A1 (en) * | 2005-06-24 | 2006-12-28 | Bhatnagar Rajendra S | Therapeutic compositions and methods using transforming growth factor-beta mimics |
-
2008
- 2008-11-05 WO PCT/IN2008/000754 patent/WO2009157010A1/fr active Application Filing
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6028222A (en) * | 1996-08-05 | 2000-02-22 | Scr Pharmatop | Stable liquid paracetamol compositions, and method for preparing same |
US20060293228A1 (en) * | 2005-06-24 | 2006-12-28 | Bhatnagar Rajendra S | Therapeutic compositions and methods using transforming growth factor-beta mimics |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US10369101B2 (en) | 2013-03-15 | 2019-08-06 | Latitude Pharmaceuticals Inc. | Parenteral diclofenac composition |
US20170304357A1 (en) * | 2016-03-30 | 2017-10-26 | Baylor University | Nutraceutical containing an oxygen-enabled composition |
US9950006B2 (en) * | 2016-03-30 | 2018-04-24 | Baylor University | Nutraceutical containing an oxygen-enabled composition |
US10137146B2 (en) * | 2016-03-30 | 2018-11-27 | Baylor University | Oxygen-enabled composition |
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