The process for making a 0.5% methyl cellulose solution is as follows: weigh 0.5g of dry methyl cellulose and dissolve it in 100ml of ddH2O/0.9% brine (0.9g NaCl in 100ml of ddH2O) to create a transparent solution. The dissolution process can be sped up by gradually adding methyl cellulose to ddH2O/0.9% saline while stirring and heating (between 50 and 65°C). Observations 1. Make sure your methylcellulose solution doesn't have any solid-liquid separation. There are no particles and the solution is transparent and homogeneous. 2. The total dissolution of methyl cellulose may take four hours or longer. It is possible to provide 0.5% MC by injection intraperitoneally or orally [1].

MC (0.5%; catalog number M0430; Sigma-Aldrich) was formulated in sterile water and administered intraperitoneally or PO at a volume of 0.01 ml/g, twice/week for 6 weeks upon acquisition of the fully kindled state. Sterile saline (SAL) was similarly administered (0.01 ml/g). Administration of 0.5% MC or SAL twice/week for 6 weeks commenced 5–7 days after the last stimulation (or sham) needed for all mice to be fully kindled. CKM were randomized to receive either 0.5% MC or SAL by the intraperitoneal (MC: n = 14; SAL: n = 12) or PO (MC: n = 5; SAL: n = 3) route. Sham-kindled mice were similarly randomized to receive either MC or SAL by the intraperitoneal (MC: n = 13; SAL: n = 12) or PO (MC: n = 5; SAL: n = 5) route. CKM were randomized into SAL or MC treatment groups and intraperitoneal or PO administration route groups based on date of acquisition of the fully kindled state such that all groups were balanced to include both mice that achieved the early and those that achieved the late kindling criterion. Sham-kindled mice were randomized within cages. Mice were stimulated or sham-stimulated 24 hours prior to each MC or SAL administration day to ensure the stability of the stage 5 seizure, consistent with our drug-screening protocols in CKM (Barker-Haliski et al., 2016, 2017a; Koneval et al., 2018). The following day, mice were administered either SAL or MC by the assigned route of administration twice weekly for 6 weeks. Health assessments were performed at four time points during the study period by a veterinarian blinded to kindling status and treatment group.[1]
Procedure for preparing 0.5% Methyl cellulose solution
Weigh 0.5g of dry Methyl cellulose and dissolve it in 100ml of ddH2O/0.9% saline solution (0.9g of NaCl dissolved in 100ml of ddH2O) to prepare a clear solution.
Note:
1) Slowly adding Methyl cellulose to ddH2O/0.9% Saline under stirring and heating (50-65 ° C) helps to accelerate dissolution.
2) Make sure there is no solid-liquid separation in the Methyl cellulose solution. The solution is in a uniform and transparent state, with no particles.
3) It may take 4 hours or longer for Methyl cellulose to be completely dissolved.
4) 0.5% Methyl cellulose solution (0.5% MC) can be used for oral administration or intraperitoneal injection.

Absorption, Distribution and Excretion
The cellulose derivatives discussed in this report are almost entirely unabsorbed. In the human digestive tract, both absorbed and absorbable products undergo minimal degradation. In humans, orally ingested methylcellulose is almost 100% excreted in feces within four days, indicating that it is not absorbed. After swallowing, it is almost entirely unabsorbed and appears unchanged in feces. It accumulates in the liver, spleen, lymph nodes, kidneys, and blood vessel walls. …It has been reported that when methylcellulose is administered intravenously to dogs and rabbits…in addition to its effects on circulating blood, the body's inability to degrade the substance leads to its retention and accumulation in the liver, spleen, lymph nodes, kidneys, and blood vessel walls. After swallowing, it is almost entirely unabsorbed and appears unchanged in feces. /cellulose ethers/

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Metabolism/Metabolites
It has been reported that when methylcellulose is administered intravenously to dogs and rabbits, in addition to its effects on circulating blood, the substance is unable to be degraded by the body, leading to its retention and accumulation in the liver, spleen, lymph nodes, kidneys, and blood vessel walls.

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Biological half-life
4.2 minutes

Interactions
…/Methylcellulose/ has been found to interact with a variety of compounds, roughly in descending order of their composition: p-hydroxybenzoic acid, p-aminobenzoic acid, methylparaben, propylparaben, and butylparaben. Non-human toxicity values The intraperitoneal LD50 in mice is 275 g/kg.

[1]. Repeated Intraperitoneal Administration of Low-Concentration Methylcellulose Leads to Systemic Histologic Lesions Without Loss of Preclinical Phenotype. J Pharmacol Exp Ther. 2019 Oct;371(1):25-35.

Methylcellulose is a polymer composed of numerous linked glucose molecules, used as a stabilizer, thickener, and emulsifier in food and cosmetics. The degree of substitution (DS) of a particular form of methylcellulose is defined as the average number of substituted hydroxyl groups on each glucose molecule, with a theoretical maximum of 3, but more commonly values ranging from 1.3 to 2.6. Pure methylcellulose is a hydrophilic white powder, soluble in cold water (but not in hot water), forming a clear, viscous solution or gel. It is marketed under various trade names for treating constipation. Like cellulose, it is indigestible, non-toxic, and non-allergenic. Methylcellulose is a methyl ether of cellulose and has laxative activity. Methylcellulose is not absorbed by the intestines; it draws large amounts of water into the colon, increasing stool viscosity, making it softer and fluffier, and stimulating intestinal smooth muscle contractions. Methylcellulose is used as an emulsifier and suspending agent in the cosmetic, pharmaceutical, and chemical industries. It is used therapeutically as a bulk-forming laxative.

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Drug Indications
When the natural secretion of tears or saliva is disrupted, solutions containing methylcellulose can be used as a substitute for tears or saliva. It is also used to treat constipation, diverticulosis, hemorrhoids, and irritable bowel syndrome. It is also used in the production of nutritional supplement capsules. Its edible and non-toxic properties make it a vegetarian alternative to gelatin.Mechanism of Action
Methylcellulose absorbs water from the gastrointestinal lumen, thereby increasing stool volume. This leads to intestinal distension and stimulates peristalsis. The water-absorbing capacity of methylcellulose may help in its treatment of diarrhea, as it further increases stool volume and consistency.
When taken with 1 or 2 cups of water, it forms a colloidal solution in the upper digestive tract; this solution loses water in the colon, forming a gel, thereby increasing stool volume and softness.Therapeutic Uses
Laxative; pharmaceutical adjuvant
…Used as a bulk-forming laxative for the treatment of chronic constipation.

Hydrophilic substances…methylcellulose…may be effective in treating watery diarrhea symptoms due to its ability to bind water and bile salts.
Medications (Veterinary): Laxatives, suspensions, acaricides.
Pharmacodynamics
It increases stool volume, thereby promoting intestinal peristalsis. It also increases the water content in the stool, making it softer and easier to pass.

VARIABLE

variable

658.341

9004-67-5

525128

Off-white to light yellow solid powder

290 to 305 °C /Film/

-1

0

11

12

31

496

0

YLGXILFCIXHCMC-UHFFFAOYSA-N

InChI=1S/C20H38O11/c1-21-9-11-13(23-3)15(24-4)18(27-7)20(30-11)31-14-12(10-22-2)29-19(28-8)17(26-6)16(14)25-5/h11-20H,9-10H2,1-8H3

2,3,4-trimethoxy-6-(methoxymethyl)-5-[3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxyoxane

methylated cellulosecellulose, methyl ether methylcellulose E461

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

H2O : ~5 mg/mL

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)