CN102908310A - Meloxicam injection for treating chronic infectious arthritis of dogs and cats - Google Patents
Meloxicam injection for treating chronic infectious arthritis of dogs and cats Download PDFInfo
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- CN102908310A CN102908310A CN2012104350077A CN201210435007A CN102908310A CN 102908310 A CN102908310 A CN 102908310A CN 2012104350077 A CN2012104350077 A CN 2012104350077A CN 201210435007 A CN201210435007 A CN 201210435007A CN 102908310 A CN102908310 A CN 102908310A
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- meloxicam
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Abstract
The invention discloses a meloxicam injection for treating chronic infectious arthritis of dogs and cats. The meloxicam injection is a meloxicam non-steroidal anti-inflammatory drug, and the administration route is intramuscular injection. The meloxicam injection for treating chronic infectious arthritis of dogs and cats has the effect of dispelling wind and eliminating dampness, tonifying kidney and repelling cold, promoting blood circulation to remove meridian obstruction and strengthening tendons and bones, and achieves remarkable effect in treating chronic infectious arthritis.
Description
Technical field
The present invention relates to a kind of ejection preparation for the treatment of dog, cat rheumatoid arthritis.Belong to the Western medicine preparation field.
Background technology
Rheumatoid arthritis is chronic progressive external, aggressivity and immune-mediated multiple arthrosis.The small-sized dog of mostly occurring at 8 monthly ages to 9 year old and enjoying with it the dog.It is relevant with immunologic mechanism.Inflammatory reaction appears in the beginning synovial membrane, as synovial membrane ooze out, edema, fibrinous deposition, synovial hyperplasia.Along with the development of disease, synovial membrane thickens, hypertrophy, forms a kind of granulation tissue of vascularization.The latter disturbs cartilage to cause chondronecrosis from the nutrition of synovial fluid, and corrodes subchondral bone, produces the local bone dissolving, and articular surface is withered.Can involve articular ligament and tendon when serious.At the beginning of the disease, general performance spirit is depressed, heating and anorexia, occurs later on walking lamely.Heavy when light during limping, repeatedly outbreak, ankylosis, several joints are often involved in arthroncus.In the later stage, articular cartilage is further corroded, and the periarticular disorganization increases the weight of and causes ligament rapture, joint deformity.So, in case suffered from rheumatoid arthritis, must active treatment, note simultaneously the conditioning of daily life, add sharp movement.
At present, the drug main for the treatment of rheumatoid arthritis will be divided into Western medicine and Chinese medicine two large classes, although conventional Chinese medicine has more satisfactory anti-inflammatory analgesic effect, can not improve basic lesion, easily produce repeatedly after the drug withdrawal, and long-term prescription easily produces untoward reaction.Therefore, the ejection preparation of a kind for the treatment of rheumatoid arthritis that has no side effect of exploitation is very necessary.
Meloxicam (meloxicam) is the new type NS AIDs of a kind of enol amide-type of being produced by the development of German Boehringer Ingelheim Boehringer Ingelheim company, its indication be osteoarthritis symptoms when increasing the weight of the short-term symptom treatment and the long-term symptom treatment of rheumatoid arthritis and mandatory spondylitis.
[1]The preparation of meloxicam is existing multiple in people's medicine field at present, and through State Food and Drug Administration's query site, the dosage form of meloxicam mainly contains conventional tablet, dispersible tablet, injection, capsule etc. at present.
Meloxicam
Existing meloxicam injection indication is osteoarthritis and rheumatic arthritis, the short-term remission of the acute exacerbation of ankylosis rachitis; Route of administration is intramuscular injection.Existing meloxicam injection is mainly by following shortcoming, standing time long time, color can be turned to be yellow slightly, through measuring, is due to its impurity component degraded, therefore controls impurity content, the stability that improves preparation has become important topic.
Summary of the invention
The present invention provides a kind of meloxicam injection for the treatment of dog, cat rheumatoid arthritis first.
Another object of the present invention provides the preparation method of described meloxicam ejection preparation.
Meloxicam injection of the present invention, every milliliter injection contains:
5.0-20 the mg meloxicam,
10-20% ethanol (v/v)
7.5-12.5% Tetrahydrofurfuryl polyethylene glycol ether (v/v)
4-6% PLURONICS F87 (w/v)
0.4-0.8%NaCl（w/v）
0.4-0.6% glycine (w/v)
0.2-0.4% meglumine (w/v)
Regulate its pH value with NaOH and hydrochloric acid,
All the other are water for injection.
The preferred pH value scope of aqueous solution is 8-10, and preferred PH scope is 8.7-8.9.
Preferably, meloxicam injection of the present invention, every milliliter injection contains:
5.0-20 the mg meloxicam,
15% ethanol (v/v)
10% Tetrahydrofurfuryl polyethylene glycol ether (v/v)
5% PLURONICS F87 (w/v)
0.6%NaCl（w/v）
0.5% glycine (w/v)
0.3% meglumine (w/v)
Regulate its pH value with NaOH and hydrochloric acid,
All the other are water for injection.
The preferred pH value scope of aqueous solution is 8-10, and preferred pH scope is 8.7-8.9.
Meloxicam injection of the present invention, its preparation method is as follows: the ethanol and the 90% dissolved in distilled water poloxamer that add first recipe quantity, add successively meloxicam and meglumine, stir on heating (about 50 ℃) limit, magnetic stirring apparatus top, until solution is clarified, adds at last sodium chloride and the glycine of recipe quantity, regulating the PH scope with the 1N sodium hydroxide solution is 8.7-8.9, distilled water is settled to full dose with flowing steam 100 degree sterilization 30min, uses suitable filter to be filtered to clear and bright, fill.
Prescription of the present invention forms through the screening acquisition, and screening process is as follows:
According to the physicochemical property of meloxicam, meloxicam is water insoluble, is dissolved in the organic solvents such as dimethyl formamide, N-Methyl pyrrolidone.The meloxicam dissolubility is relevant with the pH value, and its dissolubility is minimum when pH4, along with the pH value raises and raises, therefore consider to add the cosolvent meglumine, having basic group in the meglumine molecule, is a kind of free alkali compounds of safety non-toxic, is commonly used for cosolvent.Under certain condition, meglumine and some hydrophobic insoluble drugs form the non-metal salt chemical compound or form molecular complex, thereby have greatly increased the dissolubility of medicine, in addition, have added ethanol, and hydrotropy and Stabilization are arranged; PLURONICS F87 is solubilizing agent, and benzyl alcohol is made antiseptic.The several key factors that affect this preparation stability have been carried out orthogonal, to determine best prescription, such as table 1
Table 1 Meloxicam Formulation table
Prescription screening and optimization
According to the result of trial test adjuvant screening, find that cosolvent, solubilizing agent, three factors of pH value all have certain impact to Meloxicam stability.Therefore form three variable factors with cosolvent, antiseptic, pH value, each factor is selected three levels, sees Table 2, presses statistical analysis (L
9) 3
3The orthogonal trial test.
The design of table 2 Three factors-levels
Processing method is just measured everywhere according to three listed factors of table 2 and is added each adjuvant, and the preparation Meloxicam 1.～9..Get sample segment and place 4 ° of C to preserve, in 1 month, have or not medicine to separate out in the observation medicinal liquid; Other gets sample segment and preserves under 60 ° of C hot conditionss, in sampling in the 10th day, investigates solution colour and changes, and measure meloxicam content.
Performance assessment criteria and standards of grading are placed injection change color behind the 10d with 60 ° of C high temperature, meloxicam content and low tempertaure storage have or not Precipitation after 1 month be performance assessment criteria, concrete standards of grading are that the every decline 0.5 of meloxicam content adds 1 minute (〉=0.25 enters,＜0.25 house); The most shallow person of color is 0 minute, and every dark color solution adds 5 minutes; Be 0 minute without Precipitation, have precipitation to add 5 minutes.
Table 3 orthogonal test observed result
As shown in Table 3, after 60 ° of C high temperature were placed 10d, 1,4, No. 7 injection color got 0 minute without significant change, and remaining injection liquid color is slightly dark, all gets 5 minutes.No. 7 injection content of 1 ~ No. 9 injection slightly change.Score the lowest in 9 kinds of prescription compages (best prescription combination) is No. 4 prescriptions, i.e. A
2B
1C
2
By the screening of prescription orthogonal test and optimization, determined that the best prescription of 0.5% Meloxicam is as follows:
Contain following material among every 100ml:
Below data further specify advantage of the present invention by experiment.
One, analgesic experiment:
Test method: adopt the randomized controlled trial method
Experimental animal is from the clinical health dog of Nanjing meat dog plant, totally 37, the principle that by age, kind and body weight are close is divided into 6 groups at random, every group 6, wherein 3 groups is dosage group (0.2 mg/kg.b.w.) in Meloxicam low dose group (0.1 mg/kg.b.w.), the Meloxicam, Meloxicam high dose group (0.4 mg/kg.b.w.), one group is analgin injection control drug group (10 mg/kg.b.w.), one group is not administration matched group, and last is organized as not processing not administration matched group.Medication is subcutaneous injection.
The foundation of pain model
Select uterus oophorectomy (OHE) as pain model.3 dosage groups of meloxicam (A, B, C group) are pressed respectively 0.1 mg/kg, 0.2 mg/kg, 0.4 mg/kg dosage subcutaneous injection Meloxicam before anesthesia; Medicine matched group (D group) is according to 10 mg/kg intramuscular injection analgin injections.
Index of assessment of curative effect
Adopt Melbourne Pain Scale (MPS) method, by observing the situations such as medication front and back physiological data, the mental status, activity, palpation response, posture, its pain is marked, the score of all dogs is added up, tabulation, the drafting pattern (see figure 1).
The middle and high dosage group of meloxicam pain score is starkly lower than meloxicam low dose group and analgin injection medicine matched group, and meloxicam low dose group pain score is higher than analgin injection medicine matched group; Pain score is lower, and analgesic effect is better.And in therapeutic process, do not find obvious adverse reaction.Therefore, result of the test shows that meloxicam uses by recommended dose, for the obvious analgesic effect of postoperative pain.
Two, stability test
The stability of the meloxicam of the present invention and prior art compares:
Table 4, stable comparative result
Description of drawings
Fig. 1: each group test dog perioperatively pain score score block diagram
The specific embodiment
Further specify by the following examples the present invention, but not as limitation of the present invention.
Embodiment 1:
| Composition | g/100ml |
| Meloxicam | 500mg |
| Meglumine | 0.5mg |
| Tetrahydrofurfuryl polyethylene glycol ether | 10ml |
| PLURONICS F87 | 5.00mg |
| Ethanol | 15ml |
| Sodium chloride | 0.6mg |
| Glycine | 0.5mg |
| Sodium hydroxide | Be adjusted to 8.7 |
| Water for injection | Add to 100ml |
Preparation technology: the ethanol and the 90% dissolved in distilled water PLURONICS F87 that add first recipe quantity, add successively meloxicam and meglumine, stir on heating (about 50 ℃) limit, magnetic stirring apparatus top, until solution clarification, the sodium chloride and the glycine that add at last recipe quantity, the 1N sodium hydroxide solution is regulated pH, and distilled water is settled to full dose with flowing steam 100 degree sterilization 30min, be filtered to suitable filter clear and bright, fill.
Embodiment 2:
| Composition | g/100ml |
| Meloxicam | 2g |
| Meglumine | 0.3mg |
| Tetrahydrofurfuryl polyethylene glycol ether | 10ml |
| PLURONICS F87 | 5mg |
| Ethanol | 15.ml |
| Sodium chloride | 0.6mg |
| Glycine | 0.5mg |
| Sodium hydroxide | Be adjusted to 8.9 |
| Water for injection | Add to 100ml |
Preparation technology: the ethanol and the 90% dissolved in distilled water poloxamer that add first recipe quantity, add successively meloxicam and meglumine, stir on heating (about 50 ℃) limit, magnetic stirring apparatus top, until solution clarification, the sodium chloride and the glycine that add at last recipe quantity, the 1N sodium hydroxide solution is regulated PH, and distilled water is settled to full dose with flowing steam 100 degree sterilization 30min, be filtered to suitable filter clear and bright, fill.
Claims (5)
1. meloxicam injection, every milliliter injection contains following component:
5.0-20 the mg meloxicam,
10-20% ethanol (v/v)
7.5-12.5% Tetrahydrofurfuryl polyethylene glycol ether (v/v)
4-6% PLURONICS F87 (w/v)
0.4-0.8%NaCl（w/v）
0.4-0.6% glycine (w/v)
0.2-0.4% meglumine (w/v)
All the other are water for injection
PH is 8-10.
2. according to claim 1 meloxicam injection, every milliliter injection contains following component:
5.0-20 the mg meloxicam,
15% ethanol (v/v)
10% Tetrahydrofurfuryl polyethylene glycol ether (v/v)
5% PLURONICS F87 (w/v)
0.6%NaCl（w/v）
0.5% glycine (w/v)
0.3% meglumine (w/v)
All the other are water for injection
PH is 8-10.
3. according to claim 1 meloxicam injection, the pH value of solution scope is 8.7-8.9.
4. according to claim 1 meloxicam injection, its specification comprises 20ml:400mg, 50ml:1g, 100ml:2g, 250ml:5g.
5. the preparation method of the meloxicam injection of claim 1, process following steps: the ethanol and the 90% dissolved in distilled water poloxamer that add first recipe quantity, add successively meloxicam and meglumine, stir on heating (about 50 ℃) limit, magnetic stirring apparatus top, until solution clarification, the sodium chloride and the glycine that add at last recipe quantity, regulating the pH scope with the 1N sodium hydroxide solution is 8.7-8.9, distilled water is settled to full dose with flowing steam 100 degree sterilization 30min, be filtered to suitable filter clear and bright, fill.
Priority Applications (1)
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| CN2012104350077A CN102908310A (en) | 2012-11-02 | 2012-11-02 | Meloxicam injection for treating chronic infectious arthritis of dogs and cats |
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| CN2012104350077A CN102908310A (en) | 2012-11-02 | 2012-11-02 | Meloxicam injection for treating chronic infectious arthritis of dogs and cats |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103690480A (en) * | 2013-12-18 | 2014-04-02 | 吉林修正药业新药开发有限公司 | Meloxicam injection for treating rheumatoid arthritis and osteoarthritis and preparation method thereof |
| CN103751767A (en) * | 2013-12-15 | 2014-04-30 | 青岛东海药业有限公司 | Medicament composition and application thereof |
| CN106551947A (en) * | 2015-09-28 | 2017-04-05 | 黄家宇 | It is a kind of to treat compound preparation of Osteoarthritis and preparation method thereof |
| WO2019214715A1 (en) * | 2018-05-11 | 2019-11-14 | 南京清普生物科技有限公司 | Meloxicam composition, preparation and preparation method and use thereof |
| CN115068419A (en) * | 2022-07-22 | 2022-09-20 | 潍坊恒邦兽药有限公司 | Veterinary high-concentration meloxicam injection and processing equipment thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1437472A (en) * | 2000-06-20 | 2003-08-20 | 贝林格尔·英格海姆维特梅迪卡有限公司 | Highly concentrated stable meloxicam solutions |
| CN1950090A (en) * | 2004-04-29 | 2007-04-18 | 贝林格尔·英格海姆维特梅迪卡有限公司 | Use of meloxicam formulations in veterinary medicine |
-
2012
- 2012-11-02 CN CN2012104350077A patent/CN102908310A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1437472A (en) * | 2000-06-20 | 2003-08-20 | 贝林格尔·英格海姆维特梅迪卡有限公司 | Highly concentrated stable meloxicam solutions |
| CN1950090A (en) * | 2004-04-29 | 2007-04-18 | 贝林格尔·英格海姆维特梅迪卡有限公司 | Use of meloxicam formulations in veterinary medicine |
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103751767A (en) * | 2013-12-15 | 2014-04-30 | 青岛东海药业有限公司 | Medicament composition and application thereof |
| CN103690480A (en) * | 2013-12-18 | 2014-04-02 | 吉林修正药业新药开发有限公司 | Meloxicam injection for treating rheumatoid arthritis and osteoarthritis and preparation method thereof |
| CN106551947A (en) * | 2015-09-28 | 2017-04-05 | 黄家宇 | It is a kind of to treat compound preparation of Osteoarthritis and preparation method thereof |
| WO2019214715A1 (en) * | 2018-05-11 | 2019-11-14 | 南京清普生物科技有限公司 | Meloxicam composition, preparation and preparation method and use thereof |
| CN110464846A (en) * | 2018-05-11 | 2019-11-19 | 南京清普生物科技有限公司 | A kind of Meloxicam composition, preparation and the preparation method and application thereof |
| JP2021521212A (en) * | 2018-05-11 | 2021-08-26 | 南京清普生物科技有限公司 | Meloxicam compositions, formulations and methods and applications thereof |
| CN110464846B (en) * | 2018-05-11 | 2023-04-18 | 南京清普生物科技有限公司 | Meloxicam composition, preparation method and application thereof |
| JP7374501B2 (en) | 2018-05-11 | 2023-11-07 | 南京清普生物科技有限公司 | Meloxicam compositions, preparations and their manufacturing methods and applications |
| CN115068419A (en) * | 2022-07-22 | 2022-09-20 | 潍坊恒邦兽药有限公司 | Veterinary high-concentration meloxicam injection and processing equipment thereof |
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Address after: 266061 Shandong city of Qingdao province high tech park of Laoshan district by the No. 29 Shandong Road, building 12F high speed Applicant after: QINGDAO VLAND BIOLOGICAL CO., LTD. Applicant after: Qingdao Conlinent Animal Pharmaceutical Co., Ltd. Address before: Dual northbound Chengyang District 266061 in Shandong Province, Qingdao City, the first Green Industrial Park continet Animal Pharmaceutical Co. Ltd. is a R & D center building Applicant before: Qingdao KDN Pharmaceutical Co., Ltd. Applicant before: Qingdao Conlinent Animal Pharmaceutical Co., Ltd. |
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Application publication date: 20130206 |