Application of oroxylum indicum general flavone in preparation of medicine for treating uveitis

Abstract

The invention discloses application of oroxylum indicum total flavonoids in preparation of a medicine for treating uveitis. Experiments prove that the eye drops taking the oroxylum indicum total flavonoids or the oroxylin A as the active ingredient can reduce the uveitis eye inflammation and retina injury degree and reduce the infiltration quantity of inflammatory cells. The oroxylum indicum general flavone is taken as an oral medicine, so that inflammatory infiltration cells of a vitreous cavity and an iris-ciliary body can be reduced, bleeding symptoms can be effectively improved, hyperplasia of iris-ciliary body tissues can be inhibited, and infiltration of leukocytes of aqueous humor in mouse eyes can be effectively inhibited.

Description

Technical Field

[0001] This invention belongs to the field of biomedical technology, and in particular relates to the application of total flavonoids from Oroxylum indicum in the preparation of drugs for treating uveitis. Background Technology

[0002] Uveitis is a heterogeneous disease characterized by inflammation within the eyeball. As one of the most important complications of intraocular inflammation, it can induce glaucoma. Because intraocular inflammation can affect surrounding tissues, inflammation of the retina (retinitis), optic disc (optic papillitis), and vitreous body (vitrectomy) is also clinically classified as uveitis. The main symptoms of uveitis include decreased vision, eye pain, redness, photophobia, and floaters, and can even lead to blindness. Spondyloarthritis, ankylosing spondylitis, and inflammatory bowel disease can all induce uveitis. Uveitis can be accompanied by various systemic diseases and is characterized by its diverse types, complex etiologies, significant clinical variability, severe vision loss, high rate of blindness, difficulty in diagnosis and treatment, long course, and high recurrence rate, seriously affecting patients' quality of life.

[0003] Anterior uveitis is the most common type of uveitis, including iritis, iridocyclitis, and anterior cyclitis. Symptoms typically include pain, redness, and blurred vision. Based on its cause, uveitis can be further divided into infectious uveitis and non-infectious uveitis. In the pathogenesis of both infectious and non-infectious uveitis, the activation of inflammatory signaling pathways and the excessive release of pro-inflammatory mediators are related to the treatment of uveitis. Therefore, inhibiting inflammatory signaling pathways and downregulating the release of pro-inflammatory mediators are important approaches to treating uveitis. Clinically, infectious uveitis requires the use of anti-inflammatory drugs in combination with drugs targeting different infectious agents to relieve symptoms. Glucocorticoids are first-line drugs for treating both infectious and non-infectious uveitis, but long-term use and discontinuation can lead to inflammatory rebound or other adverse reactions, such as increased intraocular pressure (potentially leading to glaucoma), accelerated cataract formation, increased susceptibility to infection, and other ocular complications. Biologics have significant advantages in treating uveitis that is unresponsive to traditional therapies, but they are costly, and long-term use can lead to immunogenicity and drug resistance, as well as other side effects such as headaches, injection site reactions, and infections. Furthermore, biologics typically require systemic or local injections, which can reduce patient compliance. Summary of the Invention

[0004] In view of the above background technology, the present invention provides the application of total flavonoids from Oroxylum indicum in the preparation of a drug for treating uveitis.

[0005] The specific technical solution of the present invention is as follows: On the one hand, the present invention provides the application of total flavonoids from Oroxylum indicum in the preparation of a medicament for treating uveitis.

[0006] Preferably, the drug is an oral medication or eye drops.

[0007] Preferably, the total flavonoids from *Oroxylum indicum* are flavonoid compounds extracted from *Oroxylum indicum*, including baicalin, baicalin, oroxylum indicum A, oroxylum indicum B, salicornin, and salicornin-7-O-glucuronide.

[0008] In the technical solution of this invention, total flavonoids from Oroxylum indicum can reduce the degree of uveitis-related eye inflammation and retinal damage, or reduce the number of inflammatory cells infiltrating.

[0009] In another aspect, the present invention provides an eye drop for treating uveitis, the eye drop comprising total flavonoids from Oroxylum indicum and excipients; or comprising total flavonoids from Oroxylum indicum, excipients and water for injection; wherein the excipients are surfactants.

[0010] Preferably, the total flavonoids from *Oroxylum indicum* are flavonoid compounds extracted from *Oroxylum indicum*, including baicalin, baicalin, oroxylum indicum A, oroxylum indicum B, salicornin, and salicornin-7-O-glucuronide.

[0011] Furthermore, the total flavonoid content of *Oroxylum indicum* in the eye drops is 0.05~0.2% m / V.

[0012] Furthermore, the excipient content in the eye drops is 99~100% V / V.

[0013] Furthermore, the excipients are selected from at least one of polyethylene glycol, polyethylene glycol-7-stearate, diethylene glycol monoethyl ether, PEG-glycerol caprylate, poly(40) stearate, polyoxyethylene (35) castor oil, polyethylene glycol 40 hydrogenated castor oil, lecithin, Tween-80, ethanol, carbomer, poloxamer, and hydroxypropyl-β and cyclodextrin.

[0014] In another aspect, the present invention provides an eye drop for treating uveitis, the eye drop comprising orbicularisoside A and excipients; or comprising orbicularisoside A, excipients and water for injection; wherein the excipients are surfactants.

[0015] Furthermore, the content of oroxylon ammodendronin A in the eye drops is 0.05~0.2% m / V.

[0016] Furthermore, the excipient content in the eye drops is 99~100% V / V.

[0017] Furthermore, the excipients are selected from at least one of polyethylene glycol, polyethylene glycol-7-stearate, diethylene glycol monoethyl ether, PEG-glycerol caprylate, poly(40) stearate, polyoxyethylene (35) castor oil, polyethylene glycol 40 hydrogenated castor oil, lecithin, Tween-80, ethanol, carbomer, poloxamer, and hydroxypropyl-β and cyclodextrin.

[0018] In another aspect, the present invention provides an oral medication for treating uveitis, comprising total flavonoids from Oroxylum indicum and excipients.

[0019] The total flavonoids from *Oroxylum indicum* are flavonoid compounds extracted from *Oroxylum indicum*, including baicalin, baicalin, oroxylum indicum A, oroxylum indicum B, salicornin, and salicornin-7-O-glucuronide.

[0020] In the technical solution of the present invention, the effective dose of total flavonoids from Oroxylum indicum in the oral medication is 40 mg / kg.

[0021] In the technical solution of the present invention, the uveitis is lipopolysaccharide (LPS)-induced uveitis.

[0022] The beneficial effects of this invention are as follows: This invention provides the application of total flavonoids from *Oroxylum indicum* in the preparation of a medicament for treating uveitis. Eye drops containing total flavonoids or oroxylum indicum glycoside A can reduce the degree of inflammation and retinal damage in uveitis-infected eyes, and decrease the number of inflammatory cells infiltrating the eye. Using total flavonoids from *Oroxylum indicum* as an oral medication for treating uveitis reduces inflammatory cells infiltrating the vitreous cavity and iridociliary body, effectively improves bleeding symptoms, inhibits the proliferation of iridociliary body tissue, and effectively inhibits leukocyte infiltration in the aqueous humor of mouse eyes. Attached Figure Description

[0023] Figure 1-2 The pathological scores and illustrations for the blank group, model group, 0.05% total flavonoids of Oroxylum indicum group, 0.2% total flavonoids of Oroxylum indicum group, and positive control group in Example 1 are shown. Figure 3-4 HE staining comparison and aqueous humor leukocyte count of the blank group, model group, 0.05% total flavonoids of Oroxylum indicum group, 0.2% total flavonoids of Oroxylum indicum group and positive control group in Example 1; Figure 5-6 The pathological scores and illustrations of the blank group, model group, 40 mg / kg total flavonoids of Oroxylum indicum group, and positive control group in Example 2 are shown below. Figure 7-8 HE staining comparison and aqueous humor leukocyte count of blank group, model group, 40 mg / kg total flavonoids of Oroxylum indicum group and positive control group in Example 2; Figure 9-10The pathological scores and illustrations for the blank group, model group, 0.05% oroxylum indicum A group, 0.2% oroxylum indicum A group, and positive control group in Example 3 are shown. Figure 11-12 HE staining comparison and aqueous humor leukocyte count of the blank group, model group, 0.05% oroxylum indicum A group, 0.2% oroxylum indicum A group and positive control group in Example 3; Figure 13 The total protein levels in the aqueous humor of the blank group, model group, 0.05% oroxylum indicum A group, 0.1% oroxylum indicum A group, 0.2% oroxylum indicum A group and positive control group were compared in Example 4. Figure 14 This study compares the total protein levels in the aqueous humor of the blank group, model group, 40 mg / kg total flavonoids group of Oroxylum indicum, and positive control group in Example 5. Detailed Implementation

[0024] The following embodiments are merely some, not all, of the embodiments of the present invention. Therefore, the detailed descriptions of the embodiments provided below are not intended to limit the scope of the claimed invention, but merely to illustrate selected embodiments. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without inventive effort are within the scope of protection of the present invention.

[0025] In this invention, unless otherwise specified, all equipment and raw materials are commercially available or commonly used in the industry. The methods described in the following embodiments are conventional methods in the art, unless otherwise specified.

[0026] In the following embodiments: 6-8 week old mice were purchased from Guangdong Provincial Laboratory Animal Center; LPS B4 was purchased from Sigma-Aldrich (USA); dexamethasone was purchased from Sigma-Aldrich (USA); RNA extraction kit was purchased from Promega (USA); BCA protein quantification kit was purchased from Thermo Fisher Scientific (USA); PBS was purchased from Sigma-Aldrich (USA); hematoxylin-eosin staining solution was purchased from Wuhan Baiqiandu Biotechnology Co., Ltd.; total flavonoids from Oroxylum indicum were purchased from Chengdu Pusi Biotechnology Co., Ltd.

[0027] In the following examples, the structural formula of oroxin A is as follows:

[0028] Example 1 Effects of total flavonoids from *Oroxylum indicum* eye drops on lipopolysaccharide (LPS)-induced experimental uveitis in mice.

[0029] I. Eight-week-old female Balb / c mice were randomly divided into five groups: sham operation group (Sham group), model group (Model group), 0.05% total flavonoids of Oroxylum indicum group, 0.2% total flavonoids of Oroxylum indicum group, and 0.025% dexamethasone sodium phosphate eye drops group (positive control group), with five mice in each group.

[0030] In the *Oroxylum indicum* total flavonoids group, the total flavonoids were diluted to the corresponding concentration (m / V) using sterile PBS and polyethylene glycol at a volume ratio of 1:1. Both the *Oroxylum indicum* total flavonoids group and the positive control group were administered the drug three times daily for the first two days before modeling, with each administration occurring 4 hours apart. During administration, 2 μL of the drug solution or dexamethasone sodium phosphate eye drops were pipetted and instilled into the mice's eyes. Modeling was initiated on the third day, following this procedure: Mice were anesthetized by intraperitoneal injection of chloral hydrate, the periorbital area was disinfected with povidone-iodine, and 2 μL of LPS B4 (diluted to 125 ng / mL with PBS) was injected into the posterior sclera of the mouse eye using a microsyringe. The LPS was injected into the vitreous cavity of the mouse eye, held for 10 seconds, and then withdrawn. The drug was administered three more times on the day of modeling, with each administration occurring 4 hours apart. Twenty-four hours after modeling, the mice were sacrificed, and their eyeballs were harvested. Six different mice from each group had their eyeballs placed in EP tubes containing paraformaldehyde and fixed for 24 hours.

[0031] II. HE Staining: The fixed eyeball samples were placed in a dehydration box for dehydration. Eyeball tissue was then embedded using a paraffin embedding machine and cooled on a -20°C freezing stage. After the paraffin block solidified, it was removed and trimmed. The trimmed paraffin block was then placed on a paraffin microtome for sectioning, with a section thickness of 4 μm. The sections were fixed onto glass slides using a slide spreader and placed in an oven at 60°C until the paraffin block melted. After removal, the slides were allowed to cool naturally. The cell nuclei and cytoplasm were stained with hematoxylin and eosin, respectively. After staining, the slides were dehydrated, mounted, and observed and photographed under a microscope.

[0032] III. Pathological Scoring: Pathological scoring is conducted based on the degree of ocular lesions (symptoms such as inflammatory cell infiltration, tissue proliferation, and hemorrhage), with a scoring range of 0-5 points. The ocular structures involved in the scoring include the vitreous cavity, aqueous humor, ciliary body, and iris. Aqueous humor white blood cell count is an important indicator of the severity of uveitis. Enlarged images of ocular sections are taken, and white blood cell counts are performed on the same sized area of ​​aqueous humor in each photograph.

[0033] The experimental results of this embodiment are as follows: Figure 1-4 As shown in the figure, the total flavonoids from *Oroxylum indicum* eye drops improved the uveitis symptoms in mice. Specifically, the number of inflammatory infiltrating cells in the vitreous cavity and iridociliary body decreased, the hemorrhage symptoms were effectively improved, the proliferation of iridociliary body tissue was effectively inhibited, and the infiltration of leukocytes in the aqueous humor of the mouse eye was effectively suppressed.

[0034] Example 2 Effects of oral administration of total flavonoids from Oroxylum indicum on lipopolysaccharide (LPS)-induced experimental uveitis in mice.

[0035] I. Eight-week-old female Balb / c mice were randomly divided into five groups: the Sham group, the Model group, the 40 mg / kg total flavonoids of Oroxylum indicum group, and the 0.025% dexamethasone sodium phosphate eye drop group (positive control group), with five mice in each group. In the Oroxylum indicum total flavonoids group, the total flavonoids were dissolved in DMSO and diluted with physiological saline to the appropriate concentration (m / V). The Oroxylum indicum total flavonoids group was administered orally once daily for two days before modeling. The positive control group was administered 0.025% dexamethasone sodium phosphate eye drops three times daily for two days before modeling, using a pipette to draw 2 μL each time. At the time of administration, the mice were weighed, and the corresponding volume of drug solution was drawn using a gavage needle and administered to the mice by gavage. On the third day, the model was established as follows: Mice were anesthetized by intraperitoneal injection of chloral hydrate. The periorbital area was disinfected with povidone-iodine. Using a microsyringe, 2 μL of LPS B4 (diluted to 125 ng / mL with PBS) was drawn and injected into the posterior sclera of the mouse eyeball. LPS was injected into the vitreous cavity of the mouse, left in place for 10 seconds, and then the needle was withdrawn to complete the model. The drug was administered once more on the day of model establishment. Twenty-four hours after model establishment, the mice were sacrificed, and their eyeballs were harvested. Six different mice from each group had their eyeballs placed in EP tubes containing paraformaldehyde and fixed for 24 hours.

[0036] II. HE Staining: The fixed eyeball samples were placed in a dehydration box for dehydration. Eyeball tissue was then embedded using a paraffin embedding machine and cooled on a -20°C freezing stage. After the paraffin block solidified, it was removed and trimmed. The trimmed paraffin block was then placed on a paraffin microtome for sectioning, with a section thickness of 4 μm. The sections were fixed onto glass slides using a slide spreader and placed in an oven at 60°C until the paraffin block melted. After removal, the slides were allowed to cool naturally. The cell nuclei and cytoplasm were stained with hematoxylin and eosin, respectively. After staining, the slides were dehydrated, mounted, and observed and photographed under a microscope.

[0037] III. Pathological Scoring: Pathological scoring is conducted based on the degree of ocular lesions (symptoms such as inflammatory cell infiltration, tissue proliferation, and hemorrhage), with a scoring range of 0-5 points. The ocular structures involved in the scoring include the vitreous cavity, aqueous humor, ciliary body, and iris. Aqueous humor white blood cell count is an important indicator of the severity of uveitis. Enlarged images of ocular sections are taken, and white blood cell counts are performed on the same sized area of ​​aqueous humor in each photograph.

[0038] The experimental results of this embodiment are as follows: Figure 5-8As shown in the figure, oral administration of total flavonoids from *Oroxylum indicum* improved uveitis symptoms in mice, specifically by reducing inflammatory infiltrating cells in the vitreous cavity and iridocillary body, effectively alleviating hemorrhage symptoms, and effectively inhibiting iridocillary tissue proliferation. Furthermore, it effectively suppressed leukocyte infiltration in the aqueous humor of the mouse eye, consistent with the experimental results of eye drops containing total flavonoids from *Oroxylum indicum*.

[0039] Example 3 Effects of oroxylon ammodendronin A eye drops on lipopolysaccharide (LPS)-induced experimental uveitis in mice.

[0040] I. Eight-week-old female Balb / c mice were randomly divided into five groups: Sham group, Model group, 0.05% oroxylin A group, 0.2% oroxylin A group, and 0.025% dexamethasone sodium phosphate eye drops group (positive control group), with five mice in each group. In the oroxylin A group, oroxylin A was diluted to the appropriate concentration (m / V) using sterile PBS and polyethylene glycol at a volume ratio of 1:1. Both the oroxylin A group and the positive control group were administered the drug three times daily for two days prior to modeling, with each administration occurring 4 hours apart. 2 μL of the drug solution or dexamethasone sodium phosphate eye drops was pipetted into the mice's eyes before administration. On the third day, the model was established as follows: Mice were anesthetized by intraperitoneal injection of chloral hydrate. The periorbital area was disinfected with povidone-iodine. Using a microsyringe, 2 μL LPS (diluted to 125 ng / mL with PBS) was drawn and injected into the posterior sclera of the mouse's eyeball. The LPS was injected into the vitreous cavity of the mouse and left in place for 10 seconds before being withdrawn, thus completing the model. The drug was administered three more times on the day of model establishment, with each administration 4 hours apart. Twenty-four hours after model establishment, the mice were sacrificed, and their eyeballs were harvested. Six different mice from each group had their eyeballs placed in EP tubes containing paraformaldehyde and fixed for 24 hours.

[0041] II. HE Staining: The fixed eyeball samples were placed in a dehydration box for dehydration. Eyeball tissue was then embedded using a paraffin embedding machine and cooled on a -20°C freezing stage. After the paraffin block solidified, it was removed and trimmed. The trimmed paraffin block was then placed on a paraffin microtome for sectioning, with a section thickness of 4 μm. The sections were fixed onto glass slides using a slide spreader and placed in an oven at 60°C until the paraffin block melted. After removal, the slides were allowed to cool naturally. The cell nuclei and cytoplasm were stained with hematoxylin and eosin, respectively. After staining, the slides were dehydrated, mounted, and observed and photographed under a microscope.

[0042] III. Pathological Scoring: Pathological scoring is conducted based on the degree of ocular lesions (symptoms such as inflammatory cell infiltration, tissue proliferation, and hemorrhage), with a scoring range of 0-5 points. The ocular structures involved in the scoring include the vitreous cavity, aqueous humor, ciliary body, and iris. Aqueous humor white blood cell count is an important indicator of the severity of uveitis. Enlarged images of ocular sections are taken, and white blood cell counts are performed on the same sized area of ​​aqueous humor in each photograph.

[0043] The experimental results of this embodiment are as follows: Figure 9-12 As shown in the figure, after intervention with oroxylum indicum A eye drops, the symptoms of uveitis in mice were improved, specifically manifested as a reduction in inflammatory infiltrating cells in the vitreous cavity and iridociliary body, effective improvement in hemorrhage symptoms, effective inhibition of iridociliary body tissue proliferation, and effective inhibition of leukocyte infiltration in the aqueous humor of mouse eyes.

[0044] Example 4 Effect of oroxylon ammodendronin A eye drops on total protein in the aqueous humor of uveitis-affected mice.

[0045] The mouse eyeballs obtained in Experiment 3 were placed in a dish, kept moist with a small amount of PBS, and 1 μL of aqueous humor was extracted by inserting a microsyringe into the anterior chamber through the cornea. The aqueous humor was diluted 40 times with physiological saline, centrifuged at 14,000 rpm for 15 min, and the supernatant was collected and temporarily stored in an EP tube (all operations were performed on ice, and the centrifuge temperature was maintained at 4℃). BCA working solution (the volume ratio of solution A to solution B was 1:50) was prepared in the dark, and 200 μL was pipetted into a 96-well plate. 25 μL of the diluted protein solution was added, the plate was vortexed to mix, and then incubated in a constant temperature incubator for 30 min. The absorbance at 570 nm was measured using a microplate reader, and the protein concentration was calculated by substituting the OD value into a standard curve.

[0046] The experimental results of this embodiment are as follows: Figure 13 As shown in the figure, under the action of LPS, the total protein level in the aqueous humor of mice increased significantly (p < 0.0001), and its content decreased after eye drops of oroxylum indicum A, thus alleviating inflammation.

[0047] Example 5 Effects of oral administration of total flavonoids from *Oroxylum indicum* on total protein in the aqueous humor of uveitis-affected mice.

[0048] The mouse eyeballs obtained in Experiment 2 were placed in a dish, kept moist with a small amount of PBS, and 1 μL of aqueous humor was extracted by inserting a microsyringe into the anterior chamber through the cornea. The aqueous humor was diluted 40 times with physiological saline, centrifuged at 14,000 rpm for 15 min, and the supernatant was collected and temporarily stored in an EP tube (all operations were performed on ice, and the centrifuge temperature was maintained at 4℃). BCA working solution (the volume ratio of solution A to solution B was 1:50) was prepared in the dark, and 200 μL was pipetted into a 96-well plate. 25 μL of the diluted protein solution was added, the plate was vortexed to mix, and then incubated in a constant temperature incubator for 30 min. The absorbance at 570 nm was measured using a microplate reader, and the protein concentration was calculated by substituting the OD value into a standard curve.

[0049] The experimental results of this embodiment are as follows: Figure 14As shown in the figure, LPS significantly increased the total protein level in the aqueous humor of mice (p < 0.0001), while oral administration of total flavonoids from *Oroxylum indicum* reduced their content and alleviated inflammation.

[0050] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. Application of total flavonoids from Oroxylum indicum in the preparation of drugs for treating uveitis.

2. The application according to claim 1, characterized in that, The medication is an oral medication or eye drops.

3. The application according to claim 1, characterized in that, The total flavonoids from *Oroxylum indicum* are flavonoid compounds extracted from *Oroxylum indicum*, including baicalin, baicalin, oroxylum indicum A, oroxylum indicum B, salicornin, and salicornin-7-O-glucuronide.

4. An eye drop for treating uveitis, characterized in that, The eye drops comprise total flavonoids from Oroxylum indicum and excipients; or, comprise total flavonoids from Oroxylum indicum, excipients, and water for injection; wherein the excipients are surfactants.

5. The eye drops according to claim 4, characterized in that, The total flavonoids from *Oroxylum indicum* are flavonoid compounds extracted from *Oroxylum indicum*, including baicalin, baicalin, oroxylum indicum glycoside A, oroxylum indicum glycoside B, succinin, and succinin-7-O-glucuronide. Preferably, the total flavonoids content of *Oroxylum indicum* in the eye drops is 0.05~0.2% m / V; Preferably, the excipient content in the eye drops is 99~100% V / V.

6. The eye drops according to claim 4, characterized in that, The excipients are selected from at least one of polyethylene glycol, polyethylene glycol-7-stearate, diethylene glycol monoethyl ether, PEG-glycerol caprylate, poly(40) stearate, polyoxyethylene (35) castor oil, polyethylene glycol 40 hydrogenated castor oil, lecithin, Tween-80, ethanol, carbomer, poloxamer, and hydroxypropyl-β and cyclodextrin.

7. An eye drop for treating uveitis, characterized in that, The eye drops comprise orbicularisoside A and excipients; or, comprise orbicularisoside A, excipients, and water for injection; wherein the excipients are surfactants.

8. The eye drops according to claim 7, characterized in that, The content of oroxylon ammodendron A in the eye drops is 0.05~0.2% m / V; Preferably, the excipient content in the eye drops is 99~100% V / V; Preferably, the excipients are selected from at least one of polyethylene glycol, polyethylene glycol-7-stearate, diethylene glycol monoethyl ether, PEG-glycerol caprylate, poly(40) stearate, polyoxyethylene (35) castor oil, polyethylene glycol 40 hydrogenated castor oil, lecithin, Tween-80, ethanol, carbomer, poloxamer, and hydroxypropyl-β and cyclodextrin.

9. An oral medication for treating uveitis, characterized in that, It includes total flavonoids from the wood butterfly plant, as well as excipients.

10. The oral medicament according to claim 9, characterized in that, The total flavonoids from *Oroxylum indicum* are flavonoid compounds extracted from *Oroxylum indicum*, including baicalin, baicalin, oroxylum indicum glycoside A, oroxylum indicum glycoside B, succinin, and succinin-7-O-glucuronide. Preferably, the effective dose of total flavonoids from *Oroxylum indicum* in the oral medication is 40 mg / kg.

Images