Cordyceps cicadae mycelium active substances, preparation method, pharmaceutical composition and application thereof

a technology cordyceps cicadae, which is applied in the field of mycelium active substances of cordyceps cicadae (c . cicadae), can solve the problems of difficult installation, small affecting the vision of patients, and dry eye symptoms, and achieves the effect of preventing corneal injury or xerophthalmia, and reducing the risk of infection

Inactive Publication Date: 2016-10-27
GRAPE KING
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0037]The present invention provides Cordyceps cicadae (C. cicadae) mycelium active substances, preparation method, and the application for treating / preventing corneal injury or xerophthalmia induced by physical or chemical damages. Compared to general treatments of xerophthalmia (medicine or eye drops), the present invention provides a much safer, easier way to prevent or treat this disease. The C. cicadae mycelium active substances of present invention are natural and are safer than other drugs.

Problems solved by technology

Deficiency or uneven distribution for any of these three layers of the tear film could cause dry eye symptoms.
1. Artificial tears: The function of artificial tears comprises wetting eyes, diluting inflammatory substances and reducing tear osmolarity, and therefore is the most common treatment for patients with xerophthalmia. If patients are allergic to preservatives or use artificial tears at a high frequency (above 4 to 6 times a day), it is recommended for patients to use preservative-free artificial tears to lubricate the eyes.
2. Autologous serum: The composition of serum proteins in tears resembles that of whole serum. Serum is rich in growth factors, and therefore can be used to treat patients with xerophthalmia as natural tear substitutes. The frozen serum can be preserved for 3 to 6 months, so the patients do not need frequent blood draws.
3. Mucolytics (mucus dissolving agents): They are medicines used to treat respiratory diseases. Mucolytics can reduce tear secretion decrease tear volume and lyse mucous plaques on the ocular surface.
4. Lacrisert: This medication is a solid artificial tear that is placed into the deepest section of lower eyelid to treat dry eyes. It works by maintaining lubrication and keeping the eye moist within 24 hrs. The disadvantage of lacrisert is that it is hard to install, and it might slightly affect patients' vision.
5. Anti-inflammatory therapy: In addition to deficiency of tears, ocular inflammation is also an important cause of xerophthalmia. Thus, use of topical steroids or Restasis (cyclosporine ophthalmic emulsion) is another treatment method. Restasis was approved by the FDA in 2002 as the only therapeutic treatment to increase tear production in patients with chronic dry eyes.
6. Antibiotics: Oral antibiotics, particularly tetracycline or doxycycline, are effective treatments for eyelid inflammation, especially for patients with rosacea. These patients treated with oral antibiotics should practice frequent eyelid hygiene and apply warm compresses. Moreover, topical vitamin A creams is another treatment option. The cream can be used before sleep but its effect is still controversial.
7. If patients have an autoimmune disease, they should also refer to a rheumatologist for evaluation.
1. Punctal plugs: This method blocks the lacrimal canaliculi to conserve the tears so that most of tears can stay on the ocular surface and stable the tear film. In general, the ophthalmologist will use absorbable inserts to tamponade at first. If this operation can reduce the symptoms of xerophthalmia, a permanent plug will be considered. If a punctal plug is to be used, patients must pay attention to inflammation as it can cause ocular surface damages.
2. Tarsorrhaphy: Patients suffering from severe dry eye, corneal ulcers, or Bell's palsy may perform Tarsorrhaphy to help protect the eye until the underlying condition can be corrected.
Compendium of Materia Medica said “The effectiveness of chán huā is similar to that of Cicada slough, which could cure malaria.” However, no one has yet produced such evidence.

Method used

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  • Cordyceps cicadae mycelium active substances, preparation method, pharmaceutical composition and application thereof
  • Cordyceps cicadae mycelium active substances, preparation method, pharmaceutical composition and application thereof
  • Cordyceps cicadae mycelium active substances, preparation method, pharmaceutical composition and application thereof

Examples

Experimental program
Comparison scheme
Effect test

example 1

Liquid culture and Preparation of C. cicadae Mycelium Active Substances

[0086]Cordyceps cicadae Mycelium:

[0087]Grow C. cicadae mycelium on plate media (Potato Dextrose Agar, PDA) at 25° C. for about 5 days.

[0088]Liquid Culture in a Flask:

[0089]Inoculate the mycelium from the plate to a flask containing media at pH 4.5, and incubate on a shaker (120 rpm) at 25° C. for 3 days (the recipe of flask media is shown in Table 2).

TABLE 2Recipe of flask mediaIngredientAmount (weight %)Sucrose2.0Yeast extract0.5Bean flour1.0

[0090]Liquid Culture in a Fermenter Tank:

[0091]The liquid media of fermenter is similar to that of the flask media (Table 2). The flask culture was inoculated to a fermenter tank at a pressure of 0.5 to 1.0 kg / cm2, an air flow rate of 0.01 to 1.5 VVM, about 25° C., pH 4.5 and a stirring speed of 10-150 rpm or air lift for 3 days. The obtained mycelium and supernatant are called fermentation liquid. The fermentation liquid includes the active substances of the present inventi...

example 2

Xerophthalmia Animal Model and Analysis

1. Establishment of a Mice Animal Model of Xerophthalmia

[0101]Experimental Animals:

[0102]Female mice at 7 to 10 weeks of age weighed 25 to 33 g (ICR strain) were purchased from BioLASCO Taiwan and maintained in Chung Shan Medical University Laboratory Animal Center on a 12-h light / dark cycle in constant temperature and humidity. Mice were given food and water ad libitum during the whole experiment.

[0103](1) Xerophthalmia Induced by Physical Damages Using a UV Lamp (UVB)

[0104]A UV lamp is bought from Vilber lourmat (model: VL-6MC). The wavelength is set to 280 nm˜320 nm, and the main peak is at 312 nm.

[0105]Before the test, the mice were randomly divided into four groups of six: a blank control group (fed saline without UVB radiation), a UVB group (fed saline with UVB radiation), a low-dose group (fed 10 mg / kg.bw C. cicadae mycelium active substances with UVB radiation) and a high-dose group (fed 100 mg / kg.bw C. cicadae mycelium active substance...

example 3

Assessment for Effectiveness of the C. cicadae Mycelium Active Substances for Preventing Xerophthalmia

[0128]1. Tear Production Test

[0129]In this test, the litmus paper with lmm width (Toyo Roshi Kaisha, Ltd) was inserted into the lower eyelid of the mouse's eye. 20 seconds later, the paper is removed and the amount of moisture is measured. The result is shown in Table. 3-1 to Table 3-4 (corresponding to FIG. 1A to 1D). The result showed that C. cicadae mycelium active substances can increase the tear production and reduce the relative tear change ratio, thus is good for preventing xerophthalmia.

TABLE 3-1The related tear change ratio (mm) of UVB mice(Corresponding with FIG. 1A)GroupDay 4Day 7Day 10Blank0.000.040.09UVB0.000.060.21 10 mg / kg · bw0.000.030.04100 mg / kg · bw0.000.060.08

TABLE 3-2The related tear change ratio (mm) of BAC mice(Corresponding with FIG. 1B)GroupDay 4Day 7Day 10Day 13Blank0.00−0.04−0.07−0.10BAC0.00−0.22−0.31−0.04 10 mg / kg · bw0.00−0.25−0.19−0.03100 mg / kg · bw0.00...

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Abstract

A method of preparing Cordyceps cicadae mycelium active substances for preventing and/or treating xerophthalmia is provided. The method comprises: (a)culturing a Cordyceps cicadae mycelium in a plate media at 15 to 35° C. for 5 to 14 days; (b)inoculating the mycelium of step(a) to a flask containing liquid media and culturing it at 15 to 35° C. with a pH of 2 to 8 for 3 days; (c)inoculating the mycelium of step(b) to a fermenter tank and culturing it at 15 to 35° C. with a pH of 2 to 8 for 3 days, so as to obtain a Cordyceps cicadae mycelium fermentation liquid; (d)freeze-drying and grating the fermentation liquid, so as to obtain a Cordyceps cicadae mycelium powder; (e)extracting the powder with solvent, so as to obtain a Cordyceps cicadae mycelium extract; and (f)drying the extract, so as to obtained the Cordyceps cicadae mycelium active substances.

Description

BACKGROUND[0001]1. Technical Field[0002]The present invention relates the development of Cordyceps cicadae (C. cicadae) mycelium active substances, in particularly relates to the application for preventing and / or treating xerophthalmia induced by physical or chemical injuries.[0003]2. Description of Related Art[0004]Dry Eye Syndrome (Xerophthalmia)[0005]“Xerophthalmia” is a common disease in Ophthalmology (eye) clinic (10-15% adult). Xerophthalmia is mainly caused by a deficiency of tears or abnormal tear composition. The general symptoms of xerophthalmia include eye dryness, fatigue, sleepiness, foreign body sensation, itching, burning and pain sensations, heavy eyelids, sticky secretions, photophobia, increased wind and external stimuli sensitivities, transient blurred vision, and excessive tearing. The severe symptoms of xerophthalmia include red, swollen, congestion, horny eye, corneal ulcer and conjunctivitis, which might affect vision if left untreated. The causes of deficienc...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): C12N1/14A61K35/66
CPCA61K35/66C12N1/14A61K36/068A61P27/02C12P1/02
Inventor LIN, PEI-CHENGCHANG, HAN-HSINCHEN, CHIN-CHUYEH, SHU-HSINGLEE, LI-YAHSU, JUI-HSIA
Owner GRAPE KING
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