Indomethacin complex preparation and use thereof in the preparation of a medicament for preventing and treating chicken bursa disease

Abstract

The application belongs to the technical field of animal medicine, and particularly relates to an indometacin compound preparation and a use thereof in preparing a medicine for preventing and treating chicken bursa disease. The indometacin compound preparation comprises indometacin, luffa, magnolia officinalis, and a pharmaceutically acceptable excipient. The scheme solves the problems of high infection rate, high mortality, and difficulty in prevention and treatment of chicken bursa disease, and improves the treatment effect on chicken bursa disease. Through optimization of the formula and the preparation method, the in-vitro dissolution of indometacin is improved, the stability of indometacin in the indometacin compound preparation is improved, and the impurity content of indometacin is reduced.

Description

Technical Field

[0001] This invention belongs to the field of animal medicine technology, specifically relating to indomethacin compound preparations and their use in the preparation of drugs for the prevention and treatment of infectious bursal disease in chickens. Background Technology

[0002] Infectious bursal disease (IBD), also known as infectious bursal disease of chickens, is a common disease caused by infectious bursal disease virus (IBDV). In susceptible flocks, newly diagnosed IBD chickens often present with acute symptoms such as cloaca pecking, reduced appetite, lethargy, ruffled feathers, drooping head and wings, drowsiness, closed eyelids, standing still in one corner, unwilling to move, unsteady gait, lying down, and forehead shaking; white or watery diarrhea, with dirt and feces around the vent, and cloaca pecking. Mortality begins to occur on the second day after infection, with the peak mortality period generally occurring on the 3rd to 4th day after infection, and recovery beginning on the 5th to 7th day. Subclinical infections do not show obvious clinical symptoms, but weight loss is observed, and sometimes specific antibodies can be detected. Chickens that are negative for maternal antibodies can be infected and develop the disease within one week of age, while chickens with maternal antibodies are more likely to be infected and develop the disease when maternal antibody levels drop to a lower level. Chickens aged 2 to 15 weeks can be infected, but chickens aged 3 to 6 weeks are most susceptible. The feces of infected chickens contain a large amount of virus, and infected chickens are the main source of infection.

[0003] IBDV can be transmitted indirectly through direct contact and contaminated feed, water, bedding, dusty equipment, vehicles, personnel, and clothing. The virus can be transmitted not only through the digestive tract, respiratory tract, and mucous membranes, but also through contaminated hatching eggs. The morbidity rate is 5%–34%, sometimes reaching as high as 74%, while the infection rate is 100%. Due to differences in the virulence and antigenicity of IBDV strains circulating in different regions, as well as variations in chicken breed, age, maternal antibodies, feeding management, nutritional status, stress factors, and post-illness measures, the mortality rate varies greatly, ranging from only 1%–5% in some areas to 15%–20% in most regions, with mortality rates reaching 64% in severely affected flocks. This infectious disease has spread rapidly in major chicken-farming countries worldwide, causing significant economic losses. After 1980, the disease was introduced to China and experienced large-scale outbreaks and sustained epidemics, severely impacting the development of China's chicken farming industry.

[0004] Chinese patent CN1544005A discloses a traditional Chinese medicine compound for the prevention and treatment of infectious bursal disease in chickens, named Qilan Kangdu Yin, whose main components include Astragalus membranaceus, Isatis indigotica root, Isatis tinctoria leaf, Rehmannia glutinosa root, and Paeonia lactiflora root. Chinese patent CN1899498A discloses a drug for the prevention and treatment of infectious bursal disease in chickens, composed of Isatis indigotica root, Isatis tinctoria leaf, Taraxacum mongolicum, Andrographis paniculata root, Lonicera japonica flower, Scutellaria baicalensis root, Forsythia suspensa fruit, Phellodendron chinense root, Gypsum fibrosum, Anemarrhena asphodeloides rhizome, Rehmannia glutinosa root, Astragalus membranaceus root, Scrophularia ningpoensis root, Agrimonia pilosa root, Rheum palmatum root, Gardenia jasminoides fruit, and Glycyrrhiza uralensis root. Chinese patent CN107213361A discloses a drug for treating infectious bursal disease in chickens. The drug is made by decocting 60g of gypsum, 30g of honeysuckle, 30g of anemarrhena, 30g of rehmannia, 25g of indigo leaves, 25g of isatis root, 20g of forsythia, 20g of gromwell root, 40g of imperata root, 30g of peony bark, 25g of licorice, 20g of bamboo leaf heart, and 50g of scrophularia root in water for 30 minutes to obtain the liquid. Chinese Patent CN113768990A discloses a traditional Chinese medicine composition for the prevention and treatment of infectious bursal disease in chickens, consisting of 100g-300g of dandelion, 100g-300g of Isatis tinctoria leaf, 100g-300g of Isatis tinctoria root, 50g-150g of honeysuckle, 50g-150g of Scutellaria baicalensis, 50g-150g of Phellodendron chinense, 50g-150g of licorice root, 30g-70g of patchouli, 30g-70g of gypsum, and 30g-70g of borax powder. The above methods for preventing and treating infectious bursal disease in chickens are all traditional Chinese medicine preparations, which have many drawbacks: (1) There are many traditional Chinese medicine ingredients, and the short digestive tract of poultry leads to low absorption rate and unsatisfactory efficacy; (2) Traditional Chinese medicine preparations have a bitter taste, and poultry have low compliance with medication, etc.

[0005] Indomethacin is an antipyretic, analgesic, and nonsteroidal anti-inflammatory drug. It has low stability in environments such as high temperatures and is generally used for inflammatory pain such as postoperative trauma, arthritis, tenosynovitis, and muscle injury. It has not been found to have any use in the treatment of infectious bursal disease in chickens. Summary of the Invention

[0006] Overcoming the shortcomings of the existing technology, this invention provides an effective drug for treating infectious bursal disease in chickens by combining traditional Chinese and Western medicine. It is composed of indomethacin, loofah sponge, magnolia bark, and pharmaceutically acceptable excipients, thus overcoming the problems of high infectivity, high mortality, and difficulty in prevention and treatment of infectious bursal disease in chickens.

[0007] The specific technical solution of this invention is as follows:

[0008] The first objective of this invention is to provide an indomethacin compound preparation, which is composed of 1-3 parts by weight of indomethacin, 20-60 parts by weight of loofah sponge, 15-50 parts by weight of magnolia bark, and pharmaceutically acceptable excipients.

[0009] In the embodiments, the indomethacin compound preparation is compound indomethacin tablets, compound indomethacin powder, or compound indomethacin mixture.

[0010] In some embodiments, the compound indomethacin tablets consist of the following components:

[0011] Indomethacin 1-3 parts by weight

[0012] 20-60 parts by weight of loofah sponge

[0013] Magnolia officinalis 15-50 parts by weight

[0014] 10-40 parts by weight of starch

[0015] 5-10 parts by weight of sucrose

[0016] 2-7 parts by weight of crospovidone

[0017] 1-4 parts by weight of talc.

[0018] The preparation method of the compound indomethacin tablets includes the following steps:

[0019] (1) Remove the residual seeds and outer skin from the loofah sponge, cut it into sections, dry it, add 1 / 3 of the prescription amount of talc powder, grind it into fine powder, pass it through a 100-mesh sieve, and obtain a loofah sponge-talc powder mixture for later use;

[0020] (2) Scrape off the rough bark of Magnolia officinalis, wash it, moisten it thoroughly, cut it into strips, dry it, add 1 / 3 of the prescription amount of talc powder, grind it into fine powder, pass it through a 100-mesh sieve, and obtain a mixture of Magnolia officinalis and talc powder for later use;

[0021] (3) Take the loofah sponge-talc mixture from step (1) and the magnolia bark-talc mixture from step (2), add indomethacin (crushed through a 100-mesh sieve), starch, sucrose, cross-linked polyvinylpyrrolidone, and the remaining talc powder, mix evenly, compress into tablets, and obtain the product.

[0022] In this embodiment, the compound indomethacin tablets may also be coated.

[0023] In some embodiments, the compound indomethacin powder comprises the following components:

[0024] Indomethacin 1-3 parts by weight

[0025] 20-60 parts by weight of loofah sponge

[0026] Magnolia officinalis 15-50 parts by weight

[0027] 220-350 parts by weight of starch.

[0028] The preparation method of the compound indomethacin powder includes the following steps:

[0029] (1) Remove the remaining seeds and outer skin from the loofah sponge, cut it into sections, dry it, grind it into fine powder, pass it through a 100-mesh sieve to obtain loofah sponge powder, and set it aside;

[0030] (2) Scrape off the rough skin of Magnolia officinalis, wash it, moisten it thoroughly, cut it into strips, dry it, grind it into fine powder, pass it through a 100-mesh sieve to obtain Magnolia officinalis powder, and set it aside;

[0031] (3) Crush indomethacin and starch, pass through a 100-mesh sieve, mix with loofah powder from step (1) and magnolia bark powder from step (2), pass through a 100-mesh sieve again, mix evenly, and you will get the product.

[0032] In some embodiments, the compound indomethacin mixture comprises the following components:

[0033] Indomethacin 1-3 parts by weight

[0034] 20-60 parts by weight of loofah sponge

[0035] Magnolia officinalis 15-50 parts by weight

[0036] 10-20 parts by weight of glycerin

[0037] 2-6 parts by weight of methylcellulose

[0038] Add an appropriate amount of water.

[0039] The preparation method of the compound indomethacin mixture includes the following steps:

[0040] (1) Remove the remaining seeds and outer skin from the loofah sponge, cut it into sections, dry it, grind it into fine powder, pass it through an 80-mesh sieve to obtain loofah sponge powder, and set it aside;

[0041] (2) Scrape off the rough skin of Magnolia officinalis, wash it, moisten it thoroughly, cut it into strips, dry it, grind it into fine powder, pass it through an 80-mesh sieve to obtain Magnolia officinalis powder, and set it aside;

[0042] (3) Dissolve methylcellulose in water and stir into a paste; crush it, mix indomethacin (passed through an 80-mesh sieve), loofah powder (step (1)), magnolia bark powder (step (2)) with glycerin, then mix with methylcellulose paste, add an appropriate amount of water, mix well, and you will get the product.

[0043] The second objective of this invention is to provide the use of the above-mentioned indomethacin compound preparation in the preparation of drugs for the prevention and treatment of infectious bursal disease in chickens.

[0044] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0045] (1) This invention utilizes the combination of Western medicine indomethacin and traditional Chinese medicine loofah and magnolia bark to improve the treatment effect of infectious bursal disease in chickens. In addition, the formula of this invention only adds two Chinese medicinal materials, which have basically no bitter taste and the poultry have good compliance with the medication.

[0046] (2) Indomethacin is a poorly soluble drug. In the preparation of compound indomethacin tablets, the present invention optimizes the process by adding some talc powder during the pretreatment of loofah sponge and magnolia bark, and adding the remaining talc powder during the subsequent mixing process. It was unexpectedly found that this can improve the in vitro dissolution of indomethacin.

[0047] (3) Indomethacin is unstable at high temperatures. In this invention, a certain amount of loofah sponge and magnolia bark are ground into fine powder and mixed with indomethacin, which improves the stability of indomethacin in the indomethacin compound preparation of this invention and reduces the impurity content of indomethacin. Attached Figure Description

[0048] Figure 1 Examples 1-3: In vitro dissolution test of compound indomethacin tablets and comparative example 4: Compound indomethacin tablets.

[0049] Figure 2 : Indomethacin impurity I, impurity II.

[0050] Figure 3 In accelerated testing, the changes in the content of related substances in Compound Indomethacin Tablets of Examples 1-3, 10, and Comparative Examples 1-5 were compared.

[0051] Figure 4 Changes in the content of related substances in Compound Indomethacin Powder (Examples 4-6) and Compound Indomethacin Mixture (Examples 7-9) during accelerated testing.

[0052] Figure 5 In the accelerated test, the changes in indomethacin content were observed in Compound Indomethacin Tablets of Examples 1-3, 10, and Comparative Examples 1-5.

[0053] Figure 6 The changes in indomethacin content in the compound indomethacin powders of Examples 4-6 and the compound indomethacin mixtures of Examples 7-9 were observed in the accelerated test. Detailed Implementation

[0054] To make the objectives and technical solutions of this invention clearer, the following embodiments are provided for further explanation. However, the scope of protection of this invention is not limited to these embodiments; the embodiments are merely for illustrative purposes. Those skilled in the art should understand that any changes or equivalent substitutions that do not depart from the concept of this invention are included within the scope of protection of this invention.

[0055] Example 1: Compound Indomethacin Tablets (200 tablets)

[0056] prescription:

[0057]

[0058] Preparation method:

[0059] (1) Remove the residual seeds and outer skin from the loofah sponge, cut it into sections, dry it, add 1 / 3 of the prescription amount of talc powder, grind it into fine powder, pass it through a 100-mesh sieve, and obtain a loofah sponge-talc powder mixture for later use;

[0060] (2) Scrape off the rough bark of Magnolia officinalis, wash it, moisten it thoroughly, cut it into strips, dry it, add 1 / 3 of the prescription amount of talc powder, grind it into fine powder, pass it through a 100-mesh sieve, and obtain a mixture of Magnolia officinalis and talc powder for later use;

[0061] (3) Take the loofah sponge-talc mixture from step (1) and the magnolia bark-talc mixture from step (2), add indomethacin (crushed through a 100-mesh sieve), starch, sucrose, cross-linked povidone, and the remaining talc, mix evenly, compress into tablets, and obtain compound indomethacin tablets.

[0062] Example 2: Compound Indomethacin Tablets (200 tablets)

[0063] prescription:

[0064]

[0065] Preparation method:

[0066] (1) Remove the residual seeds and outer skin from the loofah sponge, cut it into sections, dry it, add 1 / 3 of the prescription amount of talc powder, grind it into fine powder, pass it through a 100-mesh sieve, and obtain a loofah sponge-talc powder mixture for later use;

[0067] (2) Scrape off the rough bark of Magnolia officinalis, wash it, moisten it thoroughly, cut it into strips, dry it, add 1 / 3 of the prescription amount of talc powder, grind it into fine powder, pass it through a 100-mesh sieve, and obtain a mixture of Magnolia officinalis and talc powder for later use;

[0068] (3) Take the loofah sponge-talc mixture from step (1) and the magnolia bark-talc mixture from step (2), add indomethacin (crushed through a 100-mesh sieve), starch, sucrose, cross-linked povidone, and the remaining talc, mix evenly, compress into tablets, and obtain compound indomethacin tablets.

[0069] Example 3: Compound Indomethacin Tablets (200 tablets)

[0070] prescription:

[0071]

[0072] Preparation method:

[0073] (1) Remove the residual seeds and outer skin from the loofah sponge, cut it into sections, dry it, add 1 / 3 of the prescription amount of talc powder, grind it into fine powder, pass it through a 100-mesh sieve, and obtain a loofah sponge-talc powder mixture for later use;

[0074] (2) Scrape off the rough bark of Magnolia officinalis, wash it, moisten it thoroughly, cut it into strips, dry it, add 1 / 3 of the prescription amount of talc powder, grind it into fine powder, pass it through a 100-mesh sieve, and obtain a mixture of Magnolia officinalis and talc powder for later use;

[0075] (3) Take the loofah sponge-talc mixture from step (1) and the magnolia bark-talc mixture from step (2), add indomethacin (crushed through a 100-mesh sieve), starch, sucrose, cross-linked povidone, and the remaining talc, mix evenly, compress into tablets, and obtain compound indomethacin tablets.

[0076] Example 4: Compound Indomethacin Powder

[0077] formula:

[0078]

[0079] Preparation method:

[0080] (1) Remove the remaining seeds and outer skin from the loofah sponge, cut it into sections, dry it, grind it into fine powder, pass it through a 100-mesh sieve to obtain loofah sponge powder, and set it aside;

[0081] (2) Scrape off the rough skin of Magnolia officinalis, wash it, moisten it thoroughly, cut it into strips, dry it, grind it into fine powder, pass it through a 100-mesh sieve to obtain Magnolia officinalis powder, and set it aside;

[0082] (3) Crush indomethacin and starch, pass through a 100-mesh sieve, mix with loofah powder from step (1) and magnolia bark powder from step (2), pass through a 100-mesh sieve again, mix evenly, and obtain compound indomethacin powder.

[0083] Example 5: Compound Indomethacin Powder

[0084] formula:

[0085]

[0086] Preparation method:

[0087] (1) Remove the remaining seeds and outer skin from the loofah sponge, cut it into sections, dry it, grind it into fine powder, pass it through a 100-mesh sieve to obtain loofah sponge powder, and set it aside;

[0088] (2) Scrape off the rough skin of Magnolia officinalis, wash it, moisten it thoroughly, cut it into strips, dry it, grind it into fine powder, pass it through a 100-mesh sieve to obtain Magnolia officinalis powder, and set it aside;

[0089] (3) Crush indomethacin and starch, pass through a 100-mesh sieve, mix with loofah powder from step (1) and magnolia bark powder from step (2), pass through a 100-mesh sieve again, mix evenly, and obtain compound indomethacin powder.

[0090] Example 6: Compound Indomethacin Powder

[0091] formula:

[0092]

[0093] Preparation method:

[0094] (1) Remove the remaining seeds and outer skin from the loofah sponge, cut it into sections, dry it, grind it into fine powder, pass it through a 100-mesh sieve to obtain loofah sponge powder, and set it aside;

[0095] (2) Scrape off the rough skin of Magnolia officinalis, wash it, moisten it thoroughly, cut it into strips, dry it, grind it into fine powder, pass it through a 100-mesh sieve to obtain Magnolia officinalis powder, and set it aside;

[0096] (3) Crush indomethacin and starch, pass through a 100-mesh sieve, mix with loofah powder from step (1) and magnolia bark powder from step (2), pass through a 100-mesh sieve again, mix evenly, and obtain compound indomethacin powder.

[0097] Example 7 Compound Indomethacin Mixture

[0098] formula:

[0099]

[0100] Preparation method:

[0101] (1) Remove the remaining seeds and outer skin from the loofah sponge, cut it into sections, dry it, grind it into fine powder, pass it through an 80-mesh sieve to obtain loofah sponge powder, and set it aside;

[0102] (2) Scrape off the rough skin of Magnolia officinalis, wash it, moisten it thoroughly, cut it into strips, dry it, grind it into fine powder, pass it through an 80-mesh sieve to obtain Magnolia officinalis powder, and set it aside;

[0103] (3) Dissolve methylcellulose in an appropriate amount of water and stir into a paste; crush the powder, mix the indomethacin (passed through an 80-mesh sieve), the loofah powder (step (1)), the magnolia bark powder (step (2)) with glycerin, then mix with the methylcellulose paste, add an appropriate amount of water, mix well, and you will get the compound indomethacin mixture.

[0104] Example 8: Compound Indomethacin Mixture

[0105] formula:

[0106]

[0107] Preparation method:

[0108] (1) Remove the remaining seeds and outer skin from the loofah sponge, cut it into sections, dry it, grind it into fine powder, pass it through an 80-mesh sieve to obtain loofah sponge powder, and set it aside;

[0109] (2) Scrape off the rough skin of Magnolia officinalis, wash it, moisten it thoroughly, cut it into strips, dry it, grind it into fine powder, pass it through an 80-mesh sieve to obtain Magnolia officinalis powder, and set it aside;

[0110] (3) Dissolve methylcellulose in an appropriate amount of water and stir into a paste; crush the powder, mix the indomethacin (passed through an 80-mesh sieve), the loofah powder (step (1)), the magnolia bark powder (step (2)) with glycerin, then mix with the methylcellulose paste, add an appropriate amount of water, mix well, and you will get the compound indomethacin mixture.

[0111] Example 9: Compound Indomethacin Mixture

[0112] formula:

[0113]

[0114] Preparation method:

[0115] (1) Remove the remaining seeds and outer skin from the loofah sponge, cut it into sections, dry it, grind it into fine powder, pass it through an 80-mesh sieve to obtain loofah sponge powder, and set it aside;

[0116] (2) Scrape off the rough skin of Magnolia officinalis, wash it, moisten it thoroughly, cut it into strips, dry it, grind it into fine powder, pass it through an 80-mesh sieve to obtain Magnolia officinalis powder, and set it aside;

[0117] (3) Dissolve methylcellulose in an appropriate amount of water and stir into a paste; crush the powder, mix the indomethacin (passed through an 80-mesh sieve), the loofah powder (step (1)), the magnolia bark powder (step (2)) with glycerin, then mix with the methylcellulose paste, add an appropriate amount of water, mix well, and you will get the compound indomethacin mixture.

[0118] Example 10 Compound Indomethacin Tablets (200 tablets)

[0119] prescription:

[0120]

[0121] Preparation method:

[0122] (1) Remove the residual seeds and outer skin from the loofah sponge, cut it into sections, dry it, add 1 / 3 of the prescription amount of talc powder, grind it into fine powder, pass it through a 100-mesh sieve, and obtain a loofah sponge-talc powder mixture for later use;

[0123] (2) Scrape off the rough bark of Magnolia officinalis, wash it, moisten it thoroughly, cut it into strips, dry it, add 1 / 3 of the prescription amount of talc powder, grind it into fine powder, pass it through a 100-mesh sieve, and obtain a mixture of Magnolia officinalis and talc powder for later use;

[0124] (3) Take the loofah sponge-talc mixture from step (1) and the magnolia bark-talc mixture from step (2), add indomethacin (crushed through a 100-mesh sieve), starch, sucrose, cross-linked polyvinylpyrrolidone, and the remaining talc powder, mix evenly, compress into tablets, and obtain plain tablets.

[0125] (4) Sucrose coating, the coating weight increases by 2.0%~5.0%, thus obtaining compound indomethacin tablets.

[0126] Comparative Example 1: Compound Indomethacin Tablets (200 tablets)

[0127] prescription:

[0128]

[0129] Preparation method:

[0130] (1) Scrape off the rough bark of Magnolia officinalis, wash it, moisten it thoroughly, cut it into strips, dry it, add 1 / 2 of the prescription amount of talc powder, grind it into fine powder, pass it through a 100-mesh sieve, and obtain a mixture of Magnolia officinalis and talc powder for later use;

[0131] (2) Take the magnolia bark-talc mixture from step (1), add indomethacin (crushed through a 100-mesh sieve), starch, sucrose, crospovidone, and the remaining talc, mix evenly, compress into tablets, and obtain compound indomethacin tablets.

[0132] Comparative Example 2: Compound Indomethacin Tablets (200 tablets)

[0133] prescription:

[0134]

[0135] Preparation method:

[0136] (1) Remove the residual seeds and outer skin from the loofah sponge, cut it into sections, dry it, add 1 / 2 of the prescription amount of talc powder, grind it into fine powder, pass it through a 100-mesh sieve, and obtain a loofah sponge-talc powder mixture for later use;

[0137] (2) Take the loofah sponge-talc mixture from step (1), add indomethacin, starch, sucrose, cross-linked povidone and the remaining talc after pulverizing through a 100-mesh sieve, mix evenly, compress into tablets, and obtain compound indomethacin tablets.

[0138] Comparative Example 3: Compound Indomethacin Tablets (200 tablets)

[0139] prescription:

[0140]

[0141] Preparation method:

[0142] (1) Remove the residual seeds and outer skin from the loofah sponge, cut it into sections, dry it, add 1 / 3 of the prescription amount of talc powder, grind it into fine powder, pass it through a 100-mesh sieve, and obtain a loofah sponge-talc powder mixture for later use;

[0143] (2) Scrape off the rough bark of Magnolia officinalis, wash it, moisten it thoroughly, cut it into strips, dry it, add 1 / 3 of the prescription amount of talc powder, grind it into fine powder, pass it through a 100-mesh sieve, and obtain a mixture of Magnolia officinalis and talc powder for later use;

[0144] (3) Take the loofah sponge-talc mixture from step (1) and the magnolia bark-talc mixture from step (2), add indomethacin (crushed through a 100-mesh sieve), starch, sucrose, cross-linked povidone, and the remaining talc, mix evenly, compress into tablets, and obtain compound indomethacin tablets.

[0145] Comparative Example 4: Compound Indomethacin Tablets (200 tablets)

[0146] prescription:

[0147]

[0148] Preparation method:

[0149] (1) Remove the remaining seeds and outer skin from the loofah sponge, cut it into sections, dry it, grind it into fine powder, pass it through a 100-mesh sieve to obtain loofah sponge powder, and set it aside;

[0150] (2) Scrape off the rough skin of Magnolia officinalis, wash it, moisten it thoroughly, cut it into strips, dry it, grind it into fine powder, pass it through a 100-mesh sieve to obtain Magnolia officinalis powder, and set it aside;

[0151] (3) Take the loofah powder from step (1) and the magnolia bark powder from step (2), add indomethacin, starch, sucrose, cross-linked povidone and talc powder that have been pulverized through a 100-mesh sieve, mix evenly, compress into tablets, and obtain compound indomethacin tablets.

[0152] Comparative Example 5: Compound Indomethacin Tablets (200 tablets)

[0153] prescription:

[0154]

[0155] Preparation method:

[0156] (1) Remove the residual seeds and outer skin from the loofah sponge, cut it into sections, dry it, add 1 / 2 of the prescription amount of talc powder, grind it into fine powder, pass it through a 100-mesh sieve, and obtain a loofah sponge-talc powder mixture for later use;

[0157] (2) Magnolia officinalis extract: Take the prescribed amount of Magnolia officinalis, scrape off the rough bark, wash, moisten thoroughly, cut into strips, dry, pulverize, soak in ethanol for 12 hours, place in a percolator, percolate with about 12 times the amount of ethanol, collect the percolate, reduce pressure to recover the ethanol to the end, obtain the concentrate, dissolve the concentrate with ethyl acetate, add activated carbon for decolorization, concentrate to dryness under vacuum pressure of -0.07Mpa and temperature of 40°C to obtain Magnolia officinalis extract;

[0158] (3) Take the loofah sponge-talc mixture from step (1) and the magnolia bark extract from step (2), add indomethacin (crushed through a 100-mesh sieve), starch, sucrose, crospovidone, and the remaining talc, mix evenly, compress into tablets, and obtain compound indomethacin tablets.

[0159] Efficacy verification of the indomethacin compound preparation of this invention in treating infectious bursal disease in chickens

[0160] In May 2023, a local chicken farmer purchased 3,000 Sanhuang chicken chicks and carried out vaccinations on schedule. After 33 days of age, more than 620 chickens began to show symptoms such as lethargy, drooping wings, and yellowish-white watery feces. They were diagnosed with infectious bursal disease and the sick chickens were immediately isolated and the site and environment were strictly disinfected.

[0161] Six hundred chickens with infectious bursal disease were divided into 12 experimental groups of 50 each: Example 1, Example 2, Example 3, Example 4, Example 7, Control Group, Positive Drug Group (1‰ Astragalus Polysaccharide Oral Solution), Comparative Example 1, Comparative Example 2, Comparative Example 3, Comparative Example 4, and Comparative Example 5. The control group was given an equal volume of physiological saline. All example and comparative example groups were given indomethacin at a dose of 0.1 mg / kg. Each group was treated with the corresponding drug for 7 days, and observed for 7 days after treatment. The treatment effect on chickens with infectious bursal disease in each group was statistically analyzed.

[0162] The cure rate, effectiveness rate, and mortality rate are determined based on the clinical symptoms of broilers after treatment (spirit, appetite, feces, respiration, etc.).

[0163] Cure rate = (number of cured patients / total number) × 100%; Effective rate = (number of cured patients + number of effective patients) / total number × 100%.

[0164] Table 1. Efficacy of indomethacin compound preparations in the treatment of infectious bursal disease in chickens.

[0165]

[0166] Table 1 shows that the indomethacin compound preparation of the present invention, which combines indomethacin with two traditional Chinese medicines, loofah sponge and magnolia bark, has a good therapeutic effect on infectious bursal disease in broilers and a low mortality rate.

[0167] Dissolution investigation of compound indomethacin tablets in Examples 1-3 and Comparative Example 4 of this invention

[0168] In vitro dissolution tests were performed on the compound indomethacin tablets of Examples 1-3 and the compound indomethacin tablet of Comparative Example 4, with a medium pH of 6.8. Figure 1 As shown, the compound indomethacin tablets in Examples 1-3 of this invention have high indomethacin dissolution and a stable dissolution process.

[0169] Stability studies of compound indomethacin preparations in Examples 1-10 and Comparative Examples 1-5 of this invention

[0170] Accelerated testing was conducted to verify the changes in the content of indomethacin-related substances and the indomethacin content in the compound indomethacin preparations of Examples 1-10 and Comparative Examples 1-5.

[0171] Indomethacin-related substances were determined by high performance liquid chromatography.

[0172] Test solution: Take compound indomethacin preparation containing 50mg of indomethacin, place it in a 100ml volumetric flask, add an appropriate amount of methanol, sonicate to dissolve indomethacin, cool, dilute to the mark with methanol, shake well, filter, accurately measure 2ml of the filtrate, place it in a 10ml volumetric flask, dilute to the mark with 50% methanol solution, and shake well.

[0173] Reference solution: Accurately measure 1 ml of the test solution and place it in a 200 ml volumetric flask. Dilute to the mark with 50% methanol solution and mix well. Sensitivity solution: Accurately measure 1 ml of the reference solution and place it in a 20 ml volumetric flask. Dilute to the mark with 50% methanol solution and mix well. Chromatographic conditions: Use octadecylsilane-bonded silica gel as the stationary phase; use 0.1 mol / L glacial acetic acid solution-acetonitrile (50:50) as the mobile phase; the detection wavelength is 228 nm; the injection volume is 50 µl. System suitability requirements: The theoretical plate number, calculated based on the indomethacin peak, should not be less than 2000, and the resolution between the indomethacin peak and adjacent impurity peaks should meet the requirements. Assay: Accurately measure the test solution and reference solution and inject them separately into the liquid chromatograph. Record the chromatogram up to three times the retention time of the main peak of the test solution. Limit: If there are impurity peaks in the chromatogram of the test solution, the sum of the areas of all impurity peaks should not exceed the area of ​​the main peak of the reference solution (0.5%).

[0174] The compound indomethacin preparations of Examples 1-10 and Comparative Examples 1-5 were placed in a constant temperature and humidity chamber with high temperature (40°C) and high humidity (relative humidity 75±5%). Samples were taken in the first, second, third and sixth months to detect the content of indomethacin-related substances. Figure 3 , Figure 4The results show that the content of indomethacin-related substances in the compound indomethacin preparations of Examples 1-10 of the present invention remains basically unchanged with storage time, and the stability is higher than that of the preparations in the comparative examples.

[0175] The indomethacin content was determined by high performance liquid chromatography.

[0176] Test solution: Take the compound indomethacin preparation, place it in a mortar and grind it finely. Grind each sample separately with approximately 35 ml of methanol, and quantitatively transfer the resulting solution to a 50 ml volumetric flask. Sonicate to dissolve the indomethacin, cool, dilute to the mark with methanol, shake well, filter, and accurately measure 5 ml of the filtrate. Place it in a 25 ml volumetric flask, dilute to the mark with 50% methanol solution, and shake well. Reference solution: Accurately weigh approximately 25 mg of indomethacin reference standard, place it in a 50 ml volumetric flask, add an appropriate amount of methanol, sonicate to dissolve, cool, dilute to the mark with methanol, and shake well. Accurately measure an appropriate amount and quantitatively dilute with 50% methanol solution to prepare a solution containing approximately 0.1 mg per ml. Chromatographic conditions: See the section on related substances. Injection volume: 20 µl. System suitability requirements: The theoretical plate number, calculated based on the indomethacin peak, should be no less than 2000, and the resolution between the indomethacin peak and adjacent impurity peaks should meet the requirements. Assay: Accurately measure the test solution and reference solution, inject them separately into the liquid chromatograph, and record the chromatograms. Calculate the content of each tablet based on peak area using the external standard method, and determine the average content.

[0177] The compound indomethacin preparations of Examples 1-10 and Comparative Examples 1-5 were placed in a constant temperature and humidity chamber with high temperature (40°C) and high humidity (75±5% relative humidity). Samples were taken in the 1st, 2nd, 3rd and 6th months to detect the indomethacin content and plot the curves. Figure 5 , Figure 6 The results show that the indomethacin content in the compound indomethacin preparations of Examples 1-10 of the present invention remains basically unchanged with storage time, and the stability is higher than that of the preparations in the comparative examples.

Claims

1. An indomethacin complex preparation for the prevention and treatment of chicken bursa disease, characterized by, The indometacin complex preparation is composed of indometacin 1-3 parts by weight, luffa 20-60 parts by weight, magnolia officinalis 15-50 parts by weight, and pharmaceutically acceptable excipient.

2. The indomethacin complex preparation according to claim 1, characterized by, The indometacin complex preparation is compound indometacin tablet, compound indometacin powder, and compound indometacin mixture.

3. The indomethacin complex preparation according to claim 2, characterized by The compound indometacin tablet is composed of: indometacin 1-3 parts by weight luffa 20-60 parts by weight magnolia officinalis 15-50 parts by weight starch 10-40 parts by weight sucrose 5-10 parts by weight cross-linked povidone 2-7 parts by weight talc 1-4 parts by weight.

4. The indomethacin complex formulation according to claim 2, characterized by, The compound indometacin powder is composed of: indometacin 1-3 parts by weight luffa 20-60 parts by weight magnolia officinalis 15-50 parts by weight starch 220-350 parts by weight.

5. The indomethacin complex formulation according to claim 2, characterized by, The compound indometacin mixture is composed of: indometacin 1-3 parts by weight luffa 20-60 parts by weight magnolia officinalis 15-50 parts by weight glycerol 10-20 parts by weight methyl cellulose 2-6 parts by weight water appropriate amount.

6. A process for the preparation of the indometacin complex preparation according to claim 3, characterized in that, The preparation method of the compound indometacin tablet comprises the following steps: (1) remove the residual seeds and peel of luffa, cut into segments, dry, add 1 / 3 of the prescription amount of talc, grind into fine powder, pass through 100 mesh sieve, obtain luffa-talc mixture, and reserve; (2) remove the rough skin of magnolia officinalis, wash, soak, cut into silk, dry, add 1 / 3 of the prescription amount of talc, grind into fine powder, pass through 100 mesh sieve, obtain magnolia officinalis-talc mixture, and reserve; (3) take the luffa-talc mixture of step (1) and the magnolia officinalis-talc mixture of step (2), add indometacin, starch, sucrose, cross-linked povidone, and the remaining talc which are all crushed and passed through 100 mesh sieve, mix uniformly, press into tablets, and obtain the compound indometacin tablet.

7. A process for the preparation of the indometacin complex preparation according to claim 4, characterized in that, The preparation method of the compound indometacin powder comprises the following steps: (1) remove the residual seeds and peel of luffa, cut into segments, dry, grind into fine powder, pass through 100 mesh sieve, obtain luffa powder, and reserve; (2) remove the rough skin of magnolia officinalis, wash, soak, cut into silk, dry, grind into fine powder, pass through 100 mesh sieve, obtain magnolia officinalis powder, and reserve; (3) crush indometacin, starch, pass through 100 mesh sieve, mix with the luffa powder of step (1) and the magnolia officinalis powder of step (2), pass through 100 mesh sieve again, mix uniformly, and obtain the compound indometacin powder.

8. A process for the preparation of the indometacin complex preparation according to claim 5, characterized in that, The preparation method of the compound indometacin mixture comprises the following steps: (1) remove the residual seeds and peel of luffa, cut into segments, dry, grind into fine powder, pass through 80 mesh sieve, obtain luffa powder, and reserve; (2) remove the rough skin of magnolia officinalis, wash, soak, cut into silk, dry, grind into fine powder, pass through 80 mesh sieve, obtain magnolia officinalis powder, and reserve; (3) dissolve methyl cellulose in water, stir into paste; crush indometacin, pass through 80 mesh sieve, mix with the luffa powder of step (1), the magnolia officinalis powder of step (2), and glycerol, mix with the methyl cellulose paste, add appropriate amount of water, mix uniformly, and obtain the compound indometacin mixture.

9. The indomethacin complex preparation according to claim 2 or 3, characterized by, The compound indometacin tablet can be coated.

10. Use of the indometacin complex preparation of claim 1 in the preparation of medicine for preventing and treating chicken bursa disease.

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